Davud Sirjani, MD

Three-dimensional (3D) printing has become a promising area of innovation in biomedical research.^1,2 Previous research in orthopedic surgery has found that customized 3D printed implants, casts, orthoses, and prosthetics (eg, prosthetic hands) matched to an individual’s unique anatomy can result in more precise placement and better surgical outcomes.^3-5 Customized prosthetics have also been found to lead to fewer complications.^3,6

Recent advances in 3D printing technology has prompted investigation from surgeons to identify how this new tool may be incorporated into patient care.^1,7 One of the most common applications of 3D printing is during preoperative planning in which surgeons gain better insight into patient-specific anatomy by using patient-specific printed models.⁸ Another promising application is the production of customized prosthetics suited to each patient’s unique anatomy.⁹ As a result, 3D printing has significantly impacted bone and cartilage restoration procedures and has the potential to completely transform the treatment of patients with debilitating musculoskeletal injuries.^3,10

The potential surrounding 3D printed prosthetics has led to their adoption by several other specialties, including otolaryngology.¹¹ The most widely used application of 3D printing among otolaryngologists is preoperative planning, and the incorporation of printed prosthetics intoreconstruction of the orbit, nasal septum, auricle, and palate has also been reported.^2,12,13 Patient-specific implants might allow otolaryngologists to better rehabilitate, reconstruct, and/or regenerate craniofacial defects using more humane procedures.¹⁴

Patients with palatomaxillary cancers are treated by prosthodontists or otolaryngologists. An impression is made with a resin–which can be painful for postoperative patients–and a prosthetic is manufactured and implanted.^15-17 Patients with cancer often see many specialists, though reconstructive care is a low priority. Many of these individuals also experience dynamic anatomic functional changes over time, leading to the need for multiple prothesis.

palatomaxillary prosthetics

This program aims to use patients’ previous computed tomography (CT) to tailor customized 3D printed palatomaxillary prosthetics to specifically fit their anatomy. Palatomaxillary defects are a source of profound disability for patients with head and neck cancers who are left with large anatomic defects as a direct result of treatment. Reconstruction of palatal defects poses unique challenges due to the complexity of patient anatomy.^18,19

3D printed prosthetics for palatomaxillary defects have not been incorporated into patient care. We reviewed previous imaging research to determine if it could be used to assist patients who struggle with their function and appearance following treatment for head and neck cancers. The primary aim was to investigate whether 3D printing was a feasible strategy for creating patient-specific palatomaxillary prosthetics. The secondary aim is to determine whether these prosthetics should be tested in the future for use in reconstruction of maxillary defects.

This study was conducted at the Veterans Affairs Palo Alto Health Care System (VAPAHCS) and was approved by the Stanford University Institutional Review Board (approval #28958, informed consent and patient contact excluded). A retrospective chart review was conducted on all patients with head and neck cancers who were treated at VAPAHCS from 2010 to 2022. Patients aged ≥ 18 years who had a palatomaxillary defect due to cancer treatment, had undergone a palatal resection, and who received treatment at any point from 2010 to 2022 were included in the review. CTs were not a specific inclusion criterion, though the quality of the scans was analyzed for eligible patients. Younger patients and those treated at VAPAHCS prior to 2010 were excluded.

There was no control group; all data was sourced from the US Department of Veterans Affairs (VA) imaging system database. Among the 3595 patients reviewed, 5 met inclusion criteria and the quality of their craniofacial anatomy CTs were analyzed. To maintain accurate craniofacial 3D modeling, CTs require a maximum of 1 mm slice thickness. Of the 5 patients who met the inclusion criteria, 4 were found to have variability in the quality of their CTs and severe defects not suitable for prosthetic reconstruction, which led to their exclusion from the study. One patient was investigated to demonstrate if making these prostheses was feasible. This patient was diagnosed with a malignant neoplasm of the hard palate, underwent a partial maxillectomy, and a palatal obturator was placed to cover the defect.

The primary data collected was patient identifiers as well as the gross anatomy and dimensions of the patients’ craniofacial anatomy, as seen in previous imaging research.²⁰ Before the imaging analysis, all personal health information was removed and the dataset was deidentified to ensure patient anonymity and noninvolvement.

CT Segmentation and 3D Printing

Using CTs of the patient’s craniofacial anatomy, we developed a model of the defects. This was achieved with deidentified CTs imported into the Food and Drug Administration (FDA)-approved computerized aid design (CAD) software, Materialise Mimics. The hard palate was segmented and isolated based off the presented scan and any holes in the image were filled using the CAD software. The model was subsequently mirrored in Materialise 3-matic to replicate an original anatomical hard palate prosthesis. The final product was converted into a 3D model and imported into Formlabs preform software to generate 3D printing supports and orient it for printing. The prosthetic was printed using FDA-approved Biocompatible Denture Base Resin by a Formlabs 3B+ printer at the Palo Alto VA Simulation Center. The 3D printed prosthesis was washed using Formlabs Form Wash 80% ethyl alcohol to remove excess resin and subsequently cured to harden the malleable resin. Supports were later removed, and the prosthesis was sanded.

The primary aim of this study was to investigate whether using CTs to create patient-specific prosthetic renderings for patients with head and neck cancer could be a feasible strategy. The CTs from the patient were successfully used to generate a 3D printed prosthesis, and the prosthesis matched the original craniofacial anatomy seen in the patient's imaging (Figure). These results demonstrate that high quality CTs can be used as a template for 3D printed prostheses for mild to moderate palatomaxillary defects.

3D Printing Costs

One liter of Denture Base Resin costs $299; prostheses use about 5 mL of resin. The average annual salary of a 3D printing technician in the United States is $42,717, or $20.54 per hour.²¹ For an experienced 3D printing technician, the time required to segment the hard palate and prepare it for 3D printing is 1 to 2 hours. The process may exceed 2 hours if the technician is presented with a lower quality CT or if the patient has a complex craniofacial anatomy.

The average time it takes to print a palatal prosthetic is 5 hours. An additional hour is needed for postprocessing, which includes washing and sanding. Therefore, the cost of the materials and labor for an average 3D printed prosthetic is about $150. A Formlabs 3B+ printer is competitively priced around $10,000. The cost for Materialise Mimics software varies, but is estimated at $16,000 at VAPAHCS. The prices for these 2 items are not included in our price estimation but should be taken into consideration.

Prosthodontist Process and Cost

The typical process of creating a palatal prosthesis by a prosthodontist begins by examining the patient, creating a stone model, then creating a wax model. Biocompatible materials are selected and processed into a mold that is trimmed and polished to the desired shape. This is followed by another patient visit to ensure the prosthesis fits properly. Follow-up care is also necessary for maintenance and comfort.

The average cost of a palatal prosthesis varies depending on the type needed (ie, metal implant, teeth replacement), the materials used, the region in which the patient is receiving care, and the complexity of the case. For complex and customizable options like those required for patients with cancer, the prostheses typically cost several thousands of dollars. The Healthcare Common Procedure Coding System code for a palatal lift prosthesis (D5955) lists prices ranging from $4000 to $8000 per prosthetic, not including the cost of the prosthodontist visits.^22,23

This program sought to determine whether imaging studies of maxillary defects are effective templates for developing 3D printed prosthetics and whether these prosthetics should be tested for future use in reconstruction of palatomaxillary defects. Our program illustrated that CTs served as feasible templates for developing hard palate prostheses for patients with palatomaxillary defects. It is important to note the CTs used were from a newer and more modern scanner and therefore yielded detailed palatal structures with higher accuracy more suitable for 3D modeling. Lower-quality CTs from the 4 patients excluded from the program were not suitable for 3D modeling. This suggests that with high-quality imaging, 3D printed prosthesis may be a viable strategy to help patients who struggle with their function following treatment for head and neck cancers.

3D printed prosthesis may also be a more patient centered and convenient option. In the traditional prosthesis creation workflow, the patient must physically bite down onto a resin (alginate or silicone) to make an impression, a very painful postoperative process that is irritating to the raw edges of the surgical bed.^15,16 Prosthodontists then create a prosthetic minus the tumor and typically secure it with clips or glue.¹⁷ Many patients also experience changes in their anatomy over time requiring them to have a new protheses created. This is particularly important in veterans with palatomaxillary defects since many VA medical centers do not have a prosthodontist on staff, making accessibility to these specialists difficult. 3D printing provides a contactless prosthetic creation process. This convenience may reduce a patient’s pain and the number of visits for which they need a specialist.

Future Directions

Additional research is needed to determine the full potential of 3D printed prosthetics. 3D printed prostheses have been effectively used for patient education in areas of presurgical planning, prosthesis creation, and trainee education.²⁴ This research represents an early step in the development of a new technology for use in otolaryngology. Specifically, many veterans with a history of head and neck cancers have sustained changes to their craniofacial anatomy following treatment. Using imaging to create 3D printed prosthetics could be very effective for these patients. Prosthetics could improve a patient’s quality of life by restoring/approximating their anatomy after cancer treatment.

Significant time and care must be taken by cancer and reconstructive surgeons to properly fit a prosthesis. Improperly fitting prosthetics leads to mucosal ulceration that then may lead to a need for fitting a new prosthetic. The advantage of 3D printed prosthetics is that they may more precisely fit the anatomy of each patient using CT results, thus potentially reducing the time needed to fit the prosthetic as well as the risk associated with an improperly fit prosthetic. 3D printed prosthesis could be used directly in the future, however, clinical trials are needed to verify its efficacy vs prosthodontic options.

Another consideration for potential future use of 3D printed prosthetics is cost. We estimated that the cost of the materials and labor of our 3D printed prosthetic to be about $150. Pricing of current molded prosthetics varies, but is often listed at several thousand dollars. Another consideration is the durability of 3D printed prosthetics vs standard prosthetics. Since we were unable to use the prosthetic in the patient, it was difficult to determine its durability. The significant cost of the 3D printer and software necessary for 3D printed prosthetics must also be considered and may be prohibitive. While many academic hospitals are considering the purchase of 3D printers and licenses, this may be challenging for resource-constrained institutions. 3D printing may also be difficult for groups without any prior experience in the field. Outsourcing to a third party is possible, though doing so adds more cost to the project. While we recognize there is a learning curve associated with adopting any new technology, it’s equally important to note that 3D printing is being rapidly integrated and has already made significant advancements in personalized medicine.^8,25,26

Limitations

This program had several limitations. First, we only obtained CTs of sufficient quality from 1 patient to generate a 3D printed prosthesis. Further research with additional patients is necessary to validate this process. Second, we were unable to trial the prosthesis in the patient because we did not have FDA approval. Additionally, it is difficult to calculate a true cost estimate for this process as materials and software costs vary dramatically across institutions as well as over time.

Conclusions

The purpose of this study was to demonstrate the possibility to develop prosthetics for the hard palate for patients suffering from palatomaxillary defects. A 3D printed prosthetic was generated that matched the patient’s craniofacial anatomy. Future research should test the feasibility of these prosthetics in patient care against a traditional prosthodontic impression. Though this is a proof-of-concept study and no prosthetics were implanted as part of this investigation, we showcase the feasibility of printing prosthetics for palatomaxillary defects. The use of 3D printed prosthetics may be a more humane process, potentially lower cost, and be more accessible to veterans.

Three-dimensional (3D) printing has become a promising area of innovation in biomedical research.^1,2 Previous research in orthopedic surgery has found that customized 3D printed implants, casts, orthoses, and prosthetics (eg, prosthetic hands) matched to an individual’s unique anatomy can result in more precise placement and better surgical outcomes.^3-5 Customized prosthetics have also been found to lead to fewer complications.^3,6

Recent advances in 3D printing technology has prompted investigation from surgeons to identify how this new tool may be incorporated into patient care.^1,7 One of the most common applications of 3D printing is during preoperative planning in which surgeons gain better insight into patient-specific anatomy by using patient-specific printed models.⁸ Another promising application is the production of customized prosthetics suited to each patient’s unique anatomy.⁹ As a result, 3D printing has significantly impacted bone and cartilage restoration procedures and has the potential to completely transform the treatment of patients with debilitating musculoskeletal injuries.^3,10

The potential surrounding 3D printed prosthetics has led to their adoption by several other specialties, including otolaryngology.¹¹ The most widely used application of 3D printing among otolaryngologists is preoperative planning, and the incorporation of printed prosthetics intoreconstruction of the orbit, nasal septum, auricle, and palate has also been reported.^2,12,13 Patient-specific implants might allow otolaryngologists to better rehabilitate, reconstruct, and/or regenerate craniofacial defects using more humane procedures.¹⁴

Patients with palatomaxillary cancers are treated by prosthodontists or otolaryngologists. An impression is made with a resin–which can be painful for postoperative patients–and a prosthetic is manufactured and implanted.^15-17 Patients with cancer often see many specialists, though reconstructive care is a low priority. Many of these individuals also experience dynamic anatomic functional changes over time, leading to the need for multiple prothesis.

palatomaxillary prosthetics

This program aims to use patients’ previous computed tomography (CT) to tailor customized 3D printed palatomaxillary prosthetics to specifically fit their anatomy. Palatomaxillary defects are a source of profound disability for patients with head and neck cancers who are left with large anatomic defects as a direct result of treatment. Reconstruction of palatal defects poses unique challenges due to the complexity of patient anatomy.^18,19

3D printed prosthetics for palatomaxillary defects have not been incorporated into patient care. We reviewed previous imaging research to determine if it could be used to assist patients who struggle with their function and appearance following treatment for head and neck cancers. The primary aim was to investigate whether 3D printing was a feasible strategy for creating patient-specific palatomaxillary prosthetics. The secondary aim is to determine whether these prosthetics should be tested in the future for use in reconstruction of maxillary defects.

This study was conducted at the Veterans Affairs Palo Alto Health Care System (VAPAHCS) and was approved by the Stanford University Institutional Review Board (approval #28958, informed consent and patient contact excluded). A retrospective chart review was conducted on all patients with head and neck cancers who were treated at VAPAHCS from 2010 to 2022. Patients aged ≥ 18 years who had a palatomaxillary defect due to cancer treatment, had undergone a palatal resection, and who received treatment at any point from 2010 to 2022 were included in the review. CTs were not a specific inclusion criterion, though the quality of the scans was analyzed for eligible patients. Younger patients and those treated at VAPAHCS prior to 2010 were excluded.

There was no control group; all data was sourced from the US Department of Veterans Affairs (VA) imaging system database. Among the 3595 patients reviewed, 5 met inclusion criteria and the quality of their craniofacial anatomy CTs were analyzed. To maintain accurate craniofacial 3D modeling, CTs require a maximum of 1 mm slice thickness. Of the 5 patients who met the inclusion criteria, 4 were found to have variability in the quality of their CTs and severe defects not suitable for prosthetic reconstruction, which led to their exclusion from the study. One patient was investigated to demonstrate if making these prostheses was feasible. This patient was diagnosed with a malignant neoplasm of the hard palate, underwent a partial maxillectomy, and a palatal obturator was placed to cover the defect.

The primary data collected was patient identifiers as well as the gross anatomy and dimensions of the patients’ craniofacial anatomy, as seen in previous imaging research.²⁰ Before the imaging analysis, all personal health information was removed and the dataset was deidentified to ensure patient anonymity and noninvolvement.

CT Segmentation and 3D Printing

Using CTs of the patient’s craniofacial anatomy, we developed a model of the defects. This was achieved with deidentified CTs imported into the Food and Drug Administration (FDA)-approved computerized aid design (CAD) software, Materialise Mimics. The hard palate was segmented and isolated based off the presented scan and any holes in the image were filled using the CAD software. The model was subsequently mirrored in Materialise 3-matic to replicate an original anatomical hard palate prosthesis. The final product was converted into a 3D model and imported into Formlabs preform software to generate 3D printing supports and orient it for printing. The prosthetic was printed using FDA-approved Biocompatible Denture Base Resin by a Formlabs 3B+ printer at the Palo Alto VA Simulation Center. The 3D printed prosthesis was washed using Formlabs Form Wash 80% ethyl alcohol to remove excess resin and subsequently cured to harden the malleable resin. Supports were later removed, and the prosthesis was sanded.

The primary aim of this study was to investigate whether using CTs to create patient-specific prosthetic renderings for patients with head and neck cancer could be a feasible strategy. The CTs from the patient were successfully used to generate a 3D printed prosthesis, and the prosthesis matched the original craniofacial anatomy seen in the patient's imaging (Figure). These results demonstrate that high quality CTs can be used as a template for 3D printed prostheses for mild to moderate palatomaxillary defects.

3D Printing Costs

One liter of Denture Base Resin costs $299; prostheses use about 5 mL of resin. The average annual salary of a 3D printing technician in the United States is $42,717, or $20.54 per hour.²¹ For an experienced 3D printing technician, the time required to segment the hard palate and prepare it for 3D printing is 1 to 2 hours. The process may exceed 2 hours if the technician is presented with a lower quality CT or if the patient has a complex craniofacial anatomy.

The average time it takes to print a palatal prosthetic is 5 hours. An additional hour is needed for postprocessing, which includes washing and sanding. Therefore, the cost of the materials and labor for an average 3D printed prosthetic is about $150. A Formlabs 3B+ printer is competitively priced around $10,000. The cost for Materialise Mimics software varies, but is estimated at $16,000 at VAPAHCS. The prices for these 2 items are not included in our price estimation but should be taken into consideration.

Prosthodontist Process and Cost

The typical process of creating a palatal prosthesis by a prosthodontist begins by examining the patient, creating a stone model, then creating a wax model. Biocompatible materials are selected and processed into a mold that is trimmed and polished to the desired shape. This is followed by another patient visit to ensure the prosthesis fits properly. Follow-up care is also necessary for maintenance and comfort.

The average cost of a palatal prosthesis varies depending on the type needed (ie, metal implant, teeth replacement), the materials used, the region in which the patient is receiving care, and the complexity of the case. For complex and customizable options like those required for patients with cancer, the prostheses typically cost several thousands of dollars. The Healthcare Common Procedure Coding System code for a palatal lift prosthesis (D5955) lists prices ranging from $4000 to $8000 per prosthetic, not including the cost of the prosthodontist visits.^22,23

This program sought to determine whether imaging studies of maxillary defects are effective templates for developing 3D printed prosthetics and whether these prosthetics should be tested for future use in reconstruction of palatomaxillary defects. Our program illustrated that CTs served as feasible templates for developing hard palate prostheses for patients with palatomaxillary defects. It is important to note the CTs used were from a newer and more modern scanner and therefore yielded detailed palatal structures with higher accuracy more suitable for 3D modeling. Lower-quality CTs from the 4 patients excluded from the program were not suitable for 3D modeling. This suggests that with high-quality imaging, 3D printed prosthesis may be a viable strategy to help patients who struggle with their function following treatment for head and neck cancers.

3D printed prosthesis may also be a more patient centered and convenient option. In the traditional prosthesis creation workflow, the patient must physically bite down onto a resin (alginate or silicone) to make an impression, a very painful postoperative process that is irritating to the raw edges of the surgical bed.^15,16 Prosthodontists then create a prosthetic minus the tumor and typically secure it with clips or glue.¹⁷ Many patients also experience changes in their anatomy over time requiring them to have a new protheses created. This is particularly important in veterans with palatomaxillary defects since many VA medical centers do not have a prosthodontist on staff, making accessibility to these specialists difficult. 3D printing provides a contactless prosthetic creation process. This convenience may reduce a patient’s pain and the number of visits for which they need a specialist.

Future Directions

Additional research is needed to determine the full potential of 3D printed prosthetics. 3D printed prostheses have been effectively used for patient education in areas of presurgical planning, prosthesis creation, and trainee education.²⁴ This research represents an early step in the development of a new technology for use in otolaryngology. Specifically, many veterans with a history of head and neck cancers have sustained changes to their craniofacial anatomy following treatment. Using imaging to create 3D printed prosthetics could be very effective for these patients. Prosthetics could improve a patient’s quality of life by restoring/approximating their anatomy after cancer treatment.

Significant time and care must be taken by cancer and reconstructive surgeons to properly fit a prosthesis. Improperly fitting prosthetics leads to mucosal ulceration that then may lead to a need for fitting a new prosthetic. The advantage of 3D printed prosthetics is that they may more precisely fit the anatomy of each patient using CT results, thus potentially reducing the time needed to fit the prosthetic as well as the risk associated with an improperly fit prosthetic. 3D printed prosthesis could be used directly in the future, however, clinical trials are needed to verify its efficacy vs prosthodontic options.

Another consideration for potential future use of 3D printed prosthetics is cost. We estimated that the cost of the materials and labor of our 3D printed prosthetic to be about $150. Pricing of current molded prosthetics varies, but is often listed at several thousand dollars. Another consideration is the durability of 3D printed prosthetics vs standard prosthetics. Since we were unable to use the prosthetic in the patient, it was difficult to determine its durability. The significant cost of the 3D printer and software necessary for 3D printed prosthetics must also be considered and may be prohibitive. While many academic hospitals are considering the purchase of 3D printers and licenses, this may be challenging for resource-constrained institutions. 3D printing may also be difficult for groups without any prior experience in the field. Outsourcing to a third party is possible, though doing so adds more cost to the project. While we recognize there is a learning curve associated with adopting any new technology, it’s equally important to note that 3D printing is being rapidly integrated and has already made significant advancements in personalized medicine.^8,25,26

Limitations

This program had several limitations. First, we only obtained CTs of sufficient quality from 1 patient to generate a 3D printed prosthesis. Further research with additional patients is necessary to validate this process. Second, we were unable to trial the prosthesis in the patient because we did not have FDA approval. Additionally, it is difficult to calculate a true cost estimate for this process as materials and software costs vary dramatically across institutions as well as over time.

Conclusions

The purpose of this study was to demonstrate the possibility to develop prosthetics for the hard palate for patients suffering from palatomaxillary defects. A 3D printed prosthetic was generated that matched the patient’s craniofacial anatomy. Future research should test the feasibility of these prosthetics in patient care against a traditional prosthodontic impression. Though this is a proof-of-concept study and no prosthetics were implanted as part of this investigation, we showcase the feasibility of printing prosthetics for palatomaxillary defects. The use of 3D printed prosthetics may be a more humane process, potentially lower cost, and be more accessible to veterans.

Three-dimensional (3D) printing has become a promising area of innovation in biomedical research.^1,2 Previous research in orthopedic surgery has found that customized 3D printed implants, casts, orthoses, and prosthetics (eg, prosthetic hands) matched to an individual’s unique anatomy can result in more precise placement and better surgical outcomes.^3-5 Customized prosthetics have also been found to lead to fewer complications.^3,6

Recent advances in 3D printing technology has prompted investigation from surgeons to identify how this new tool may be incorporated into patient care.^1,7 One of the most common applications of 3D printing is during preoperative planning in which surgeons gain better insight into patient-specific anatomy by using patient-specific printed models.⁸ Another promising application is the production of customized prosthetics suited to each patient’s unique anatomy.⁹ As a result, 3D printing has significantly impacted bone and cartilage restoration procedures and has the potential to completely transform the treatment of patients with debilitating musculoskeletal injuries.^3,10

The potential surrounding 3D printed prosthetics has led to their adoption by several other specialties, including otolaryngology.¹¹ The most widely used application of 3D printing among otolaryngologists is preoperative planning, and the incorporation of printed prosthetics intoreconstruction of the orbit, nasal septum, auricle, and palate has also been reported.^2,12,13 Patient-specific implants might allow otolaryngologists to better rehabilitate, reconstruct, and/or regenerate craniofacial defects using more humane procedures.¹⁴

Patients with palatomaxillary cancers are treated by prosthodontists or otolaryngologists. An impression is made with a resin–which can be painful for postoperative patients–and a prosthetic is manufactured and implanted.^15-17 Patients with cancer often see many specialists, though reconstructive care is a low priority. Many of these individuals also experience dynamic anatomic functional changes over time, leading to the need for multiple prothesis.

palatomaxillary prosthetics

This program aims to use patients’ previous computed tomography (CT) to tailor customized 3D printed palatomaxillary prosthetics to specifically fit their anatomy. Palatomaxillary defects are a source of profound disability for patients with head and neck cancers who are left with large anatomic defects as a direct result of treatment. Reconstruction of palatal defects poses unique challenges due to the complexity of patient anatomy.^18,19

3D printed prosthetics for palatomaxillary defects have not been incorporated into patient care. We reviewed previous imaging research to determine if it could be used to assist patients who struggle with their function and appearance following treatment for head and neck cancers. The primary aim was to investigate whether 3D printing was a feasible strategy for creating patient-specific palatomaxillary prosthetics. The secondary aim is to determine whether these prosthetics should be tested in the future for use in reconstruction of maxillary defects.

This study was conducted at the Veterans Affairs Palo Alto Health Care System (VAPAHCS) and was approved by the Stanford University Institutional Review Board (approval #28958, informed consent and patient contact excluded). A retrospective chart review was conducted on all patients with head and neck cancers who were treated at VAPAHCS from 2010 to 2022. Patients aged ≥ 18 years who had a palatomaxillary defect due to cancer treatment, had undergone a palatal resection, and who received treatment at any point from 2010 to 2022 were included in the review. CTs were not a specific inclusion criterion, though the quality of the scans was analyzed for eligible patients. Younger patients and those treated at VAPAHCS prior to 2010 were excluded.

There was no control group; all data was sourced from the US Department of Veterans Affairs (VA) imaging system database. Among the 3595 patients reviewed, 5 met inclusion criteria and the quality of their craniofacial anatomy CTs were analyzed. To maintain accurate craniofacial 3D modeling, CTs require a maximum of 1 mm slice thickness. Of the 5 patients who met the inclusion criteria, 4 were found to have variability in the quality of their CTs and severe defects not suitable for prosthetic reconstruction, which led to their exclusion from the study. One patient was investigated to demonstrate if making these prostheses was feasible. This patient was diagnosed with a malignant neoplasm of the hard palate, underwent a partial maxillectomy, and a palatal obturator was placed to cover the defect.

The primary data collected was patient identifiers as well as the gross anatomy and dimensions of the patients’ craniofacial anatomy, as seen in previous imaging research.²⁰ Before the imaging analysis, all personal health information was removed and the dataset was deidentified to ensure patient anonymity and noninvolvement.

CT Segmentation and 3D Printing

Using CTs of the patient’s craniofacial anatomy, we developed a model of the defects. This was achieved with deidentified CTs imported into the Food and Drug Administration (FDA)-approved computerized aid design (CAD) software, Materialise Mimics. The hard palate was segmented and isolated based off the presented scan and any holes in the image were filled using the CAD software. The model was subsequently mirrored in Materialise 3-matic to replicate an original anatomical hard palate prosthesis. The final product was converted into a 3D model and imported into Formlabs preform software to generate 3D printing supports and orient it for printing. The prosthetic was printed using FDA-approved Biocompatible Denture Base Resin by a Formlabs 3B+ printer at the Palo Alto VA Simulation Center. The 3D printed prosthesis was washed using Formlabs Form Wash 80% ethyl alcohol to remove excess resin and subsequently cured to harden the malleable resin. Supports were later removed, and the prosthesis was sanded.

The primary aim of this study was to investigate whether using CTs to create patient-specific prosthetic renderings for patients with head and neck cancer could be a feasible strategy. The CTs from the patient were successfully used to generate a 3D printed prosthesis, and the prosthesis matched the original craniofacial anatomy seen in the patient's imaging (Figure). These results demonstrate that high quality CTs can be used as a template for 3D printed prostheses for mild to moderate palatomaxillary defects.

3D Printing Costs

One liter of Denture Base Resin costs $299; prostheses use about 5 mL of resin. The average annual salary of a 3D printing technician in the United States is $42,717, or $20.54 per hour.²¹ For an experienced 3D printing technician, the time required to segment the hard palate and prepare it for 3D printing is 1 to 2 hours. The process may exceed 2 hours if the technician is presented with a lower quality CT or if the patient has a complex craniofacial anatomy.

The average time it takes to print a palatal prosthetic is 5 hours. An additional hour is needed for postprocessing, which includes washing and sanding. Therefore, the cost of the materials and labor for an average 3D printed prosthetic is about $150. A Formlabs 3B+ printer is competitively priced around $10,000. The cost for Materialise Mimics software varies, but is estimated at $16,000 at VAPAHCS. The prices for these 2 items are not included in our price estimation but should be taken into consideration.

Prosthodontist Process and Cost

The typical process of creating a palatal prosthesis by a prosthodontist begins by examining the patient, creating a stone model, then creating a wax model. Biocompatible materials are selected and processed into a mold that is trimmed and polished to the desired shape. This is followed by another patient visit to ensure the prosthesis fits properly. Follow-up care is also necessary for maintenance and comfort.

The average cost of a palatal prosthesis varies depending on the type needed (ie, metal implant, teeth replacement), the materials used, the region in which the patient is receiving care, and the complexity of the case. For complex and customizable options like those required for patients with cancer, the prostheses typically cost several thousands of dollars. The Healthcare Common Procedure Coding System code for a palatal lift prosthesis (D5955) lists prices ranging from $4000 to $8000 per prosthetic, not including the cost of the prosthodontist visits.^22,23

This program sought to determine whether imaging studies of maxillary defects are effective templates for developing 3D printed prosthetics and whether these prosthetics should be tested for future use in reconstruction of palatomaxillary defects. Our program illustrated that CTs served as feasible templates for developing hard palate prostheses for patients with palatomaxillary defects. It is important to note the CTs used were from a newer and more modern scanner and therefore yielded detailed palatal structures with higher accuracy more suitable for 3D modeling. Lower-quality CTs from the 4 patients excluded from the program were not suitable for 3D modeling. This suggests that with high-quality imaging, 3D printed prosthesis may be a viable strategy to help patients who struggle with their function following treatment for head and neck cancers.

3D printed prosthesis may also be a more patient centered and convenient option. In the traditional prosthesis creation workflow, the patient must physically bite down onto a resin (alginate or silicone) to make an impression, a very painful postoperative process that is irritating to the raw edges of the surgical bed.^15,16 Prosthodontists then create a prosthetic minus the tumor and typically secure it with clips or glue.¹⁷ Many patients also experience changes in their anatomy over time requiring them to have a new protheses created. This is particularly important in veterans with palatomaxillary defects since many VA medical centers do not have a prosthodontist on staff, making accessibility to these specialists difficult. 3D printing provides a contactless prosthetic creation process. This convenience may reduce a patient’s pain and the number of visits for which they need a specialist.

Future Directions

Additional research is needed to determine the full potential of 3D printed prosthetics. 3D printed prostheses have been effectively used for patient education in areas of presurgical planning, prosthesis creation, and trainee education.²⁴ This research represents an early step in the development of a new technology for use in otolaryngology. Specifically, many veterans with a history of head and neck cancers have sustained changes to their craniofacial anatomy following treatment. Using imaging to create 3D printed prosthetics could be very effective for these patients. Prosthetics could improve a patient’s quality of life by restoring/approximating their anatomy after cancer treatment.

Significant time and care must be taken by cancer and reconstructive surgeons to properly fit a prosthesis. Improperly fitting prosthetics leads to mucosal ulceration that then may lead to a need for fitting a new prosthetic. The advantage of 3D printed prosthetics is that they may more precisely fit the anatomy of each patient using CT results, thus potentially reducing the time needed to fit the prosthetic as well as the risk associated with an improperly fit prosthetic. 3D printed prosthesis could be used directly in the future, however, clinical trials are needed to verify its efficacy vs prosthodontic options.

Another consideration for potential future use of 3D printed prosthetics is cost. We estimated that the cost of the materials and labor of our 3D printed prosthetic to be about $150. Pricing of current molded prosthetics varies, but is often listed at several thousand dollars. Another consideration is the durability of 3D printed prosthetics vs standard prosthetics. Since we were unable to use the prosthetic in the patient, it was difficult to determine its durability. The significant cost of the 3D printer and software necessary for 3D printed prosthetics must also be considered and may be prohibitive. While many academic hospitals are considering the purchase of 3D printers and licenses, this may be challenging for resource-constrained institutions. 3D printing may also be difficult for groups without any prior experience in the field. Outsourcing to a third party is possible, though doing so adds more cost to the project. While we recognize there is a learning curve associated with adopting any new technology, it’s equally important to note that 3D printing is being rapidly integrated and has already made significant advancements in personalized medicine.^8,25,26

Limitations

This program had several limitations. First, we only obtained CTs of sufficient quality from 1 patient to generate a 3D printed prosthesis. Further research with additional patients is necessary to validate this process. Second, we were unable to trial the prosthesis in the patient because we did not have FDA approval. Additionally, it is difficult to calculate a true cost estimate for this process as materials and software costs vary dramatically across institutions as well as over time.

Conclusions

The purpose of this study was to demonstrate the possibility to develop prosthetics for the hard palate for patients suffering from palatomaxillary defects. A 3D printed prosthetic was generated that matched the patient’s craniofacial anatomy. Future research should test the feasibility of these prosthetics in patient care against a traditional prosthodontic impression. Though this is a proof-of-concept study and no prosthetics were implanted as part of this investigation, we showcase the feasibility of printing prosthetics for palatomaxillary defects. The use of 3D printed prosthetics may be a more humane process, potentially lower cost, and be more accessible to veterans.

High-risk patients with a growing mass require proper assessment, including a thorough history, physical examination, and fine-needle aspiration for diagnosis.

A 65-year-old Vietnam veteran with a history of posttraumatic stress disorder (PTSD), transient ischemic attack, alcohol dependence, and a smoking history of 50 pack-years presents with a neck mass that has been growing for 2 months and unintentional weight loss of 25 pounds over 6 months. What is the differential diagnosis? How does a general practitioner evaluate, manage, and efficiently triage this patient?

Such cases, in which a head and neck cancer (HNC) diagnosis is suspected, can be unnerving for both physician and patient. However, knowledgeable general practitioners (GPs) can play a pivotal role in recognizing high-risk patients, initiating workups, and referring to appropriate specialists, resulting in earlier detection and potentially better outcomes.

This article outlines the authors’ recommended best practices for GPs treating patients with presumed HNC. Although the focus here is on the veteran population, in which HNC rates are significantly higher, many of the suggestions presented are applicable to the general population.

Background

Head and neck cancers represent a diverse family of malignancies of the nasopharynx, oropharynx, hypopharynx, larynx, oral cavity, paranasal sinuses, and salivary glands. This article does not cover thyroid, ophthalmologic, neurologic, or skin malignancies. The yearly worldwide incidence of all HNC cases is more than 550,000.¹ In the U.S., 55,000 new HNC cases, representing 3% of all new malignancies, are reported annually. The 5-year survival rate is 60%, but 12,000 Americans die each year of head and neck cancer.² Most HNCs occur in males aged ≥ 50 years, and the incidence increases with age. Almost $3.6 billion is spent treating HNC in the U.S. annually.³

Risk Factors

Alcohol and tobacco consumption strongly predisposes patients to squamous cell carcinoma (SCC), which accounts for 90% of HNCs. Together, alcohol and tobacco act multiplicatively.^4,5 For instance, heavy drinkers (≥ 10 drinks daily) are at 5-fold increased risk for oral and pharyngeal cancers, heavy smokers (≥ 1 pack daily) are at 20-fold increased risk, and people who both drink and smoke heavily are at 50-fold increased risk.⁶ Head and neck cancer rates are significantly elevated even for moderate/light drinkers and smokers.

Veterans have disproportionately high rates of alcohol drinking and tobacco smoking,^7,8 in part because these habits are ingrained in military culture. During World Wars I and II, tobacco companies supplied soldiers with daily rations of cigarettes,⁹ and advertisers targeted military personnel by linking smoking with patriotism, strength, and toughness.¹⁰ The VHA and the DoD reported that 33% of veterans and active-duty service personnel smoke—compared with 23% of civilians.¹¹ Vietnam veterans, 47% of whom smoke, are at particular risk for HNC.¹²

Cessation of alcohol drinking and tobacco smoking is essential for overall prognosis, especially after HNC has been diagnosed. Continued smoking after HNC treatment increases the recurrence rate 4-fold.¹³ There also is mounting evidence that cessation of drinking and smoking can reverse the risk for HNC over time. According to a meta-analysis, quitting smoking for just 1 year begins to lower the risk for HNC. Quitting smoking for 20 years reduces the risk to the level of never smokers, and abstaining from alcohol for 20 years decreases the risk by nearly 40%.¹⁴

Viral infections are risk factors for development of oral cavity, oropharyngeal, laryngeal, and nasopharyngeal carcinoma (NPC). Sixty percent of oropharyngeal cancers are positive for human papillomavirus (HPV) infection,¹⁵ and most NPCs are associated with prior Epstein-Barr virus (EBV) exposure, particularly in populations from southern China, Southeast Asia, North Africa, and the Middle East.¹⁶

Evaluation

Workup of a possible HNC starts with taking a thorough history. Early HNC symptoms that may prompt a patient to seek medical care include neck mass, nonhealing oral ulcer, voice change, sore throat for more than 2 weeks, ear pain, nasal obstruction, serous otitis media, dysphagia, and odynophagia. Patients with advanced HNC may present with unintentional weight loss, decreased appetite, and cranial nerve deficits. For alcohol or tobacco users who present with any of the symptoms, SCC should lead the differential diagnosis, prompting examination of the head and neck. The authors present a general outline for performing this examination and detail the most common types of HNC encountered in the GP setting.

Physical Examination

The GP should perform a bimanual examination of the oral cavity, ears, nose, thyroid, and cranial nerve function with the help of a headlight. The physician should use 2 tongue blades to explore the oral cavity and palpate for suspicious oral lesions. It is often possible to feel a lesion before visualizing it on the base of the tongue. If there is a presenting mass, the physician should document the mass site, size, shape, consistency, tenderness, mobility, and accompanying deficits or symptoms.

Also recommended is a thorough examination of the facial, submandibular, and other cervical lymph nodes. The drainage patterns of these nodes can help the GP track potential routes of malignant infiltration. The submental and submandibular lymph nodes (level 1) drain the lower lip, floor of mouth, anterior tongue, and side of nose. The nodes along the mid and internal jugular vein (levels 2-4) and between the sternocleidomastoid and trapezius muscles (level 5) drain the oropharynx, mid tongue, larynx, hypopharynx, parotid gland, and skin of the face and ear. Nontender hard nodes are more likely to be malignant, as are nodes of the posterior triangle (level 5).¹⁷

Malignancy by Site

Oral cavity. The oral cavity includes the lips, buccal mucosa, teeth, gums, anterior two-thirds of tongue, floor of mouth, alveolar ridge, retromolar trigone, and hard palate. The oral cavity is the most common site for HNCs.¹⁸ The most common symptoms of malignancy of the oral cavity include dysphonia, nonhealing oral ulcers, loose teeth, bleeding, change in denture fit, and chin numbness, which could indicate mandibular invasion with inferior alveolar nerve involvement.¹⁹

For thorough assessment of the oral cavity, the patient should remove all temporary dental appliances. Then, with a tongue blade in each hand, the physician should thoroughly examine the oral mucosa, moving the tongue laterally to evaluate the floor of mouth, and palpate the mucosal surfaces to identify submucosal cancers in the posterior tongue and floor of mouth. Minor salivary glands are ubiquitous in the oral cavity and may be involved by cancer. Ulcerated painful lesions that last longer than 2 weeks are less likely to be common viral or aphthous ulcers. For either an oral cavity mass or a nonhealing ulcer that persists more than 4 weeks, malignancy should be suspected, and the patient should be referred for imaging and biopsy.

Leukoplakias are white patches in the oral cavity that develop from squamous epithelial hyperplasia and cannot be scraped away with a tonghpvue blade. The lesions are usually benign, but, if there is an element of redness (erythroplakia), the risk for harboring dysplasia is much higher, though the differential diagnosis includes trauma from adjacent teeth or lichen planus. If leukoplakia is seen, the physician should accurately note the size, location, and site and should monitor every 3 to 4 months. If erythroplakia, enlargement of leukoplakia, or any evidence of mucosal invasion is noted, the physician should refer to otolaryngologyhead and neck surgery (Oto-HNS). The authors advise against lasering leukoplakia; it is unnecessary, can make subsequent evaluation more difficult, and can mask recurrent malignancy.

Oropharynx. The oropharynx includes the posterior third of tongue, soft palate, palatine and lingual tonsils, and the posterior and lateral pharyngeal walls superior to tip of epiglottis. Cancers can arise in any of these locations and may present with dysphagia, odynophagia, referred
otalgia, hoarseness, and enlarged lymph nodes. In advanced cases, there may be bleeding, airway obstruction, and aspiration. Nonsmokers with oropharyngeal SCC are likely to be HPV positive and may be younger than the typical patient with alcohol- or tobacco-related HNC. Human papillomavirus positive oropharyngeal carcinoma has a much better prognosis than its tobaccorelated counterpart does. Physical examination should include assessment of tonsillar size and symmetry, palpation of neck lymph nodes, and palpation of base of tongue. Treatment may involve surgery, radiation, or chemoradiation, depending on factors such as extent of disease and comorbidities.

Nasopharynx. The nasopharynx extends from the nasal cavity (posterior to nasal septum) to the oropharynx. The most common NPC symptoms are middle-ear effusion and enlarged neck nodes. Nasal obstruction, epistaxis, or cranial nerve deficits also may occur. The nasopharynx
is best assessed with a fiberoptic scope. Most NPCs are associated with EBV infection, and viral levels can be used to monitor response to treatment.20 Early biopsy is indicated if a nasopharyngeal mass is found.

Larynx. As with the nasopharynx, the larynx is best seen with a fiberoptic scope. Malignancy generally presents with hoarseness, voice changes, cough, sore throat, or, if more advanced, airway compromise such as stridor and neck adenopathy. As larynx HNCs may be associated
with aspiration, the authors recommend asking “Does food go down the wrong pipe?” or “Do you cough when you eat?” and having the patient drink and document any difficulty. A smoker with hoarseness lasting more than 2 weeks should be referred to Oto-HNS for endoscopic assessment. Among veterans, other causes of hoarseness include polyps,Candida infection associated with inhalation of steroids for chronic obstructive pulmonary disease, and recurrent nerve paralysis from thyroid or lung cancer.

Neck. Patients with HNCs commonly present with a neck mass. Fifty percent to 80% of adults with a nontender neck mass are harboring a malignancy.^21,22 In a patient without HIV, a neck mass larger than 2 cm should be evaluated for cancer, especially if the mass is hard and nontender.²³ Computed tomography (CT) is recommended for initial evaluation, which, if there is FNA confirmed carcinoma, should be followed by positron emission tomography (PET). If there is concern for parotidor skull base tumors, magnetic resonance imaging (MRI) is preferable for demonstrating soft-tissue definition and disease extent.

If the patient is aged < 40 years and lymph nodes have been present for less than 2 to 4 weeks, are tender, or are associated with fever or poor dental hygiene, then an infection may instead be the cause. Dentistry referral and/or an antibiotic trial should be considered. Lymphomas, also common in the neck, may be accompanied by “B symptoms” (fever, night sweats, unintentional weight loss of > 10%).²⁴ If lymphoma is suspected, fine-needle aspiration (FNA) for cytology and flow cytometry should be performed. If lymphoma is confirmed, the GP should refer the patient to an appropriate medical oncologist for further evaluation, which may include referral to Oto-HNS for core or open biopsy. Contraindications to FNA of a neck mass include paragangliomas, such as a carotid body tumor.

Other cancers of the upper aerodigestive tract also often spread to the neck nodes and may initially present as a neck mass. A thorough examination can usually point to the primary cancer, and FNA will provide the diagnosis with high specificity and sensitivity.²⁵ Midline cystic neck masses in close proximity to the hyoid bone are likely thyroglossal duct cysts. If these cysts grow, they likely require removal.

Salivary glands. The submandibular, sublingual, and parotid are the major salivary glands. There also are hundreds of small salivary glands scattered through the oral and pharyngeal mucosa. Tumors arising from the salivary glands represent about 6% of all head and neck masses; these tumors are nearly 3 times more common in men than in women.²⁶ About 80% of salivary gland tumors originate in the parotid gland; patients with such tumors typically present with a painless parotid mass.²⁶ In advanced cases, patients may present with skin infiltration and facial paralysis secondary to involvement of
the facial nerve that courses through the parotid gland after it exits the temporal bone near the mastoid tip.

Salivary gland tumors are most commonly benign, and pleomorphic adenomas are the most common benign parotid neoplasm.²⁷ The incidence of malignancy is highest in submandibular, sublingual, and minor salivary glands. There are numerous primary salivary gland malignancies, such as mucoepidermoid carcinoma, adenocarcinoma, and adenoid cystic carcinoma. Facial skin SCC may metastasize to periparotid nodes. There are also multiple nonneoplastic causes of salivary gland inflammation. Recurrent diffuse, painful gland enlargement may be suggestive of recurrent sialadenitis and may be
secondary to a stone or xerostomia associated with dehydration or use of diuretics, antidepressants, or lithium. Multiple lymphoepithelial cysts may be associated with HIV and do not require resection.²⁸

Management

After taking a thorough history and performing a physical examination, the physician evaluating a patient for HNC should proceed with diagnostic testing followed by referral to a specialist.

Diagnostic Testing
Laboratory values. Although laboratory values are unlikely to help in evaluation of a malignancy, elevated white blood cell count, erythrocyte sedimentation
rate, and C-reactive protein level are markers of a general inflammatory process that may support a clinically suspected diagnosis of infection. Values that decrease over time may represent progress toward disease resolution.²⁹

Imaging. If malignancy is suspected, imaging should be obtained. Imaging has an important role in corroborating examination findings of a mass. Imaging
also provides an accurate baseline assessment of tumor size and extent. Recommended imaging modalities include:

• Ultrasonography (US). This quick and inexpensive modality can be used to visualize suspicious neck lesions. It is helpful in performing real-time assessments and differentiating cysts from solid masses and abscesses from reactive lymph nodes or infiltrative tumors. Challenges with US include its inability to penetrate bone and practitioners’ variable interpretation of images. A different modality invariably is needed to document location and spread of suspected HNC.
• MRI and CT. These are necessary for HNC evaluation and staging. Generally, they are equivalent in node assessment, but MRI is preferable in tongue and pharynx evaluation, and CT is preferable in the larynx. An ideal image should extend from the skull base to the clavicles, demonstrating the extent of the primary tumor and potential metastases to the neck nodes. As MRI is best protocoled by an experienced head and neck radiologist, it is preferable to refer the patient to such a specialist and allow Oto-HNS to arrange the imaging. Contraindications to MRI include pacemakers and shrapnel (common among veteran patients) and claustrophobia (common among patients with PTSD).
• PET-CT. This modality helps in staging, detecting distant metastases, assessing treatment response after chemoradiation, and locating the primary cancer when a proven neck metastasis has no obvious source. Whether PET-CT should be performed before initial referral should be discussed with the specialist. A case with a proven distant metastasis likely is not operable and would be better served with a referral to medical oncology.

Biopsy. For almost all HNCs, the initial biopsy modality should be FNA. Although intraoral lesions may benefit from incisional biopsy, this procedure should not delay triage and may be outside the scope of practice for many GPs. A GP can arrange for FNA to be performed before the referral appointment. This modality has excellent diagnostic sensitivity and specificity.^30,31 In the setting of equivocal or negative results despite a high index of suspicion, having a more experienced cytopathologist repeat the FNA is often warranted. Excisional biopsy may be warranted if FNA is nondiagnostic or lymphoma is diagnosed.

Other Interventions

In some cases, the GP has additional important roles— in preparing the patient for the possibility of surgery, treating related conditions, helping the patient cope with this new medical challenge, improving nutrition, and promoting cessation of alcohol drinking and tobacco smoking.

Surgery. For patients with biopsy-proven HNC, preoperative assessment by the GP helps provide clearance for surgery, reduces time to treatment, and lessens the likelihood of postoperative complications. A recent study found that VA patients aged ≥ 70 years had a 30-day postoperative mortality rate of 6% and at least a ≥ 20% risk for a major complication during their hospital stay.³² Given these risks and the overall higher rate of chronic diseases among veterans, the authors recommend preoperative evaluation of comorbidities with particular emphasis on cardiac, renal, and pulmonary status. In addition, specific examinations (eg, electrocardiogram, chest radiograph, basic laboratory tests, liver profile test) are recommended for patients with a history of alcohol abuse.

Malnutrition. At initial diagnosis, many patients with HNC have significant weight loss.33 Unfortunately, the required complex treatment modalities increase malnutrition rates and decrease quality of life.³⁴ Preventive strategies are, therefore, key in improving patients’ overall health. The authors recommend that GPs consider early nutritional consultations and as-needed speech therapy evaluations to provide preventive strategies and exercises to maintain proper swallowing function.³⁵ Patients who are unable to eat because of aspiration caused by a large tumor should be admitted for preoperative gastric tube placement to improve nutrition and, ultimately, surgical outcome. A large percentage of veterans with HNC also have depression, which may lead to decreased appetite.³⁶ Mental health consultations can help in these circumstances, as can use of mirtazapine, which increases appetite and treats depression-related symptoms.

Pain. Nonsteroidal anti-inflammatory drugs (NSAIDs) can be recommended for relief of uncontrolled mild to moderate pain, but they must be discontinued 1 week before surgery to reduce the risk for bleeding complications. The NSAIDs should be avoided entirely in patients with untreated friable tumors of the aerodigestive tract. In patients with biopsy-proven cancer, pain control can involve opiates per World Health Organization guidelines.³⁷ Patients with head and neck SCC often have neuropathic pain, which is more effectively treated with gabapentin.

Alcohol drinking and tobacco smoking. Promoting cessation of these habits is essential for all patients, including those already diagnosed with cancer. Encouraging cessation as well as overall healthy lifestyle choices can reduce cancer risk and improve overall health—and may be the single most efficacious intervention a physician can offer.

Referral

Most patients with suspected HNC should be referred to Oto-HNS. In cases in which lymphoma is most highly suspected, medical oncology is the most appropriate initial referral. Early dental consultation is also necessary if an obturator will be needed (eg, as with a hard palate malignancy) or if irradiation is planned (radiation-induced xerostomia significantly increases the risk for dental caries).³⁸ For all new cancer diagnoses, the GP can contact the Oto-HNS specialist for help in tailoring the patient evaluation to the practices and resources at the GP’s home institution and reduce time to treatment.

Conclusion

General practitioners are essential in identifying and triaging veterans with HNC. High-risk patients with a growing mass require proper assessment, including a thorough history and physical examination, FNA for diagnosis, and appropriate specialist referral. Although this article provides a helpful framework for thinking about patients with HNC, the authors encourage GPs to check the National Comprehensive Cancer Network guidelines for additional information on the topics covered here. With this knowledge, GPs can improve outcomes for veterans with HNC.

Author disclosures
The authors report no actual or potential conflicts of interest with regard to this article.

Disclaimer
The opinions expressed herein are those of the authors and do not necessarily reflect those of Federal Practitioner, Frontline Medical Communications Inc., the U.S. Government, or any of its agencies. This article may discuss unlabeled or investigational use of certain drugs. Please review complete prescribing information for specific drugs or drug combinations—including indications, contraindications, warnings, and adverse effects—before administering pharmacologic therapy to patients.

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High-risk patients with a growing mass require proper assessment, including a thorough history, physical examination, and fine-needle aspiration for diagnosis.

A 65-year-old Vietnam veteran with a history of posttraumatic stress disorder (PTSD), transient ischemic attack, alcohol dependence, and a smoking history of 50 pack-years presents with a neck mass that has been growing for 2 months and unintentional weight loss of 25 pounds over 6 months. What is the differential diagnosis? How does a general practitioner evaluate, manage, and efficiently triage this patient?

Such cases, in which a head and neck cancer (HNC) diagnosis is suspected, can be unnerving for both physician and patient. However, knowledgeable general practitioners (GPs) can play a pivotal role in recognizing high-risk patients, initiating workups, and referring to appropriate specialists, resulting in earlier detection and potentially better outcomes.

This article outlines the authors’ recommended best practices for GPs treating patients with presumed HNC. Although the focus here is on the veteran population, in which HNC rates are significantly higher, many of the suggestions presented are applicable to the general population.

Background

Head and neck cancers represent a diverse family of malignancies of the nasopharynx, oropharynx, hypopharynx, larynx, oral cavity, paranasal sinuses, and salivary glands. This article does not cover thyroid, ophthalmologic, neurologic, or skin malignancies. The yearly worldwide incidence of all HNC cases is more than 550,000.¹ In the U.S., 55,000 new HNC cases, representing 3% of all new malignancies, are reported annually. The 5-year survival rate is 60%, but 12,000 Americans die each year of head and neck cancer.² Most HNCs occur in males aged ≥ 50 years, and the incidence increases with age. Almost $3.6 billion is spent treating HNC in the U.S. annually.³

Risk Factors

Alcohol and tobacco consumption strongly predisposes patients to squamous cell carcinoma (SCC), which accounts for 90% of HNCs. Together, alcohol and tobacco act multiplicatively.^4,5 For instance, heavy drinkers (≥ 10 drinks daily) are at 5-fold increased risk for oral and pharyngeal cancers, heavy smokers (≥ 1 pack daily) are at 20-fold increased risk, and people who both drink and smoke heavily are at 50-fold increased risk.⁶ Head and neck cancer rates are significantly elevated even for moderate/light drinkers and smokers.

Veterans have disproportionately high rates of alcohol drinking and tobacco smoking,^7,8 in part because these habits are ingrained in military culture. During World Wars I and II, tobacco companies supplied soldiers with daily rations of cigarettes,⁹ and advertisers targeted military personnel by linking smoking with patriotism, strength, and toughness.¹⁰ The VHA and the DoD reported that 33% of veterans and active-duty service personnel smoke—compared with 23% of civilians.¹¹ Vietnam veterans, 47% of whom smoke, are at particular risk for HNC.¹²

Cessation of alcohol drinking and tobacco smoking is essential for overall prognosis, especially after HNC has been diagnosed. Continued smoking after HNC treatment increases the recurrence rate 4-fold.¹³ There also is mounting evidence that cessation of drinking and smoking can reverse the risk for HNC over time. According to a meta-analysis, quitting smoking for just 1 year begins to lower the risk for HNC. Quitting smoking for 20 years reduces the risk to the level of never smokers, and abstaining from alcohol for 20 years decreases the risk by nearly 40%.¹⁴

Viral infections are risk factors for development of oral cavity, oropharyngeal, laryngeal, and nasopharyngeal carcinoma (NPC). Sixty percent of oropharyngeal cancers are positive for human papillomavirus (HPV) infection,¹⁵ and most NPCs are associated with prior Epstein-Barr virus (EBV) exposure, particularly in populations from southern China, Southeast Asia, North Africa, and the Middle East.¹⁶

Evaluation

Workup of a possible HNC starts with taking a thorough history. Early HNC symptoms that may prompt a patient to seek medical care include neck mass, nonhealing oral ulcer, voice change, sore throat for more than 2 weeks, ear pain, nasal obstruction, serous otitis media, dysphagia, and odynophagia. Patients with advanced HNC may present with unintentional weight loss, decreased appetite, and cranial nerve deficits. For alcohol or tobacco users who present with any of the symptoms, SCC should lead the differential diagnosis, prompting examination of the head and neck. The authors present a general outline for performing this examination and detail the most common types of HNC encountered in the GP setting.

Physical Examination

The GP should perform a bimanual examination of the oral cavity, ears, nose, thyroid, and cranial nerve function with the help of a headlight. The physician should use 2 tongue blades to explore the oral cavity and palpate for suspicious oral lesions. It is often possible to feel a lesion before visualizing it on the base of the tongue. If there is a presenting mass, the physician should document the mass site, size, shape, consistency, tenderness, mobility, and accompanying deficits or symptoms.

Also recommended is a thorough examination of the facial, submandibular, and other cervical lymph nodes. The drainage patterns of these nodes can help the GP track potential routes of malignant infiltration. The submental and submandibular lymph nodes (level 1) drain the lower lip, floor of mouth, anterior tongue, and side of nose. The nodes along the mid and internal jugular vein (levels 2-4) and between the sternocleidomastoid and trapezius muscles (level 5) drain the oropharynx, mid tongue, larynx, hypopharynx, parotid gland, and skin of the face and ear. Nontender hard nodes are more likely to be malignant, as are nodes of the posterior triangle (level 5).¹⁷

Malignancy by Site

Oral cavity. The oral cavity includes the lips, buccal mucosa, teeth, gums, anterior two-thirds of tongue, floor of mouth, alveolar ridge, retromolar trigone, and hard palate. The oral cavity is the most common site for HNCs.¹⁸ The most common symptoms of malignancy of the oral cavity include dysphonia, nonhealing oral ulcers, loose teeth, bleeding, change in denture fit, and chin numbness, which could indicate mandibular invasion with inferior alveolar nerve involvement.¹⁹

For thorough assessment of the oral cavity, the patient should remove all temporary dental appliances. Then, with a tongue blade in each hand, the physician should thoroughly examine the oral mucosa, moving the tongue laterally to evaluate the floor of mouth, and palpate the mucosal surfaces to identify submucosal cancers in the posterior tongue and floor of mouth. Minor salivary glands are ubiquitous in the oral cavity and may be involved by cancer. Ulcerated painful lesions that last longer than 2 weeks are less likely to be common viral or aphthous ulcers. For either an oral cavity mass or a nonhealing ulcer that persists more than 4 weeks, malignancy should be suspected, and the patient should be referred for imaging and biopsy.

Leukoplakias are white patches in the oral cavity that develop from squamous epithelial hyperplasia and cannot be scraped away with a tonghpvue blade. The lesions are usually benign, but, if there is an element of redness (erythroplakia), the risk for harboring dysplasia is much higher, though the differential diagnosis includes trauma from adjacent teeth or lichen planus. If leukoplakia is seen, the physician should accurately note the size, location, and site and should monitor every 3 to 4 months. If erythroplakia, enlargement of leukoplakia, or any evidence of mucosal invasion is noted, the physician should refer to otolaryngologyhead and neck surgery (Oto-HNS). The authors advise against lasering leukoplakia; it is unnecessary, can make subsequent evaluation more difficult, and can mask recurrent malignancy.

Oropharynx. The oropharynx includes the posterior third of tongue, soft palate, palatine and lingual tonsils, and the posterior and lateral pharyngeal walls superior to tip of epiglottis. Cancers can arise in any of these locations and may present with dysphagia, odynophagia, referred
otalgia, hoarseness, and enlarged lymph nodes. In advanced cases, there may be bleeding, airway obstruction, and aspiration. Nonsmokers with oropharyngeal SCC are likely to be HPV positive and may be younger than the typical patient with alcohol- or tobacco-related HNC. Human papillomavirus positive oropharyngeal carcinoma has a much better prognosis than its tobaccorelated counterpart does. Physical examination should include assessment of tonsillar size and symmetry, palpation of neck lymph nodes, and palpation of base of tongue. Treatment may involve surgery, radiation, or chemoradiation, depending on factors such as extent of disease and comorbidities.

Nasopharynx. The nasopharynx extends from the nasal cavity (posterior to nasal septum) to the oropharynx. The most common NPC symptoms are middle-ear effusion and enlarged neck nodes. Nasal obstruction, epistaxis, or cranial nerve deficits also may occur. The nasopharynx
is best assessed with a fiberoptic scope. Most NPCs are associated with EBV infection, and viral levels can be used to monitor response to treatment.20 Early biopsy is indicated if a nasopharyngeal mass is found.

Larynx. As with the nasopharynx, the larynx is best seen with a fiberoptic scope. Malignancy generally presents with hoarseness, voice changes, cough, sore throat, or, if more advanced, airway compromise such as stridor and neck adenopathy. As larynx HNCs may be associated
with aspiration, the authors recommend asking “Does food go down the wrong pipe?” or “Do you cough when you eat?” and having the patient drink and document any difficulty. A smoker with hoarseness lasting more than 2 weeks should be referred to Oto-HNS for endoscopic assessment. Among veterans, other causes of hoarseness include polyps,Candida infection associated with inhalation of steroids for chronic obstructive pulmonary disease, and recurrent nerve paralysis from thyroid or lung cancer.

Neck. Patients with HNCs commonly present with a neck mass. Fifty percent to 80% of adults with a nontender neck mass are harboring a malignancy.^21,22 In a patient without HIV, a neck mass larger than 2 cm should be evaluated for cancer, especially if the mass is hard and nontender.²³ Computed tomography (CT) is recommended for initial evaluation, which, if there is FNA confirmed carcinoma, should be followed by positron emission tomography (PET). If there is concern for parotidor skull base tumors, magnetic resonance imaging (MRI) is preferable for demonstrating soft-tissue definition and disease extent.

If the patient is aged < 40 years and lymph nodes have been present for less than 2 to 4 weeks, are tender, or are associated with fever or poor dental hygiene, then an infection may instead be the cause. Dentistry referral and/or an antibiotic trial should be considered. Lymphomas, also common in the neck, may be accompanied by “B symptoms” (fever, night sweats, unintentional weight loss of > 10%).²⁴ If lymphoma is suspected, fine-needle aspiration (FNA) for cytology and flow cytometry should be performed. If lymphoma is confirmed, the GP should refer the patient to an appropriate medical oncologist for further evaluation, which may include referral to Oto-HNS for core or open biopsy. Contraindications to FNA of a neck mass include paragangliomas, such as a carotid body tumor.

Other cancers of the upper aerodigestive tract also often spread to the neck nodes and may initially present as a neck mass. A thorough examination can usually point to the primary cancer, and FNA will provide the diagnosis with high specificity and sensitivity.²⁵ Midline cystic neck masses in close proximity to the hyoid bone are likely thyroglossal duct cysts. If these cysts grow, they likely require removal.

Salivary glands. The submandibular, sublingual, and parotid are the major salivary glands. There also are hundreds of small salivary glands scattered through the oral and pharyngeal mucosa. Tumors arising from the salivary glands represent about 6% of all head and neck masses; these tumors are nearly 3 times more common in men than in women.²⁶ About 80% of salivary gland tumors originate in the parotid gland; patients with such tumors typically present with a painless parotid mass.²⁶ In advanced cases, patients may present with skin infiltration and facial paralysis secondary to involvement of
the facial nerve that courses through the parotid gland after it exits the temporal bone near the mastoid tip.

Salivary gland tumors are most commonly benign, and pleomorphic adenomas are the most common benign parotid neoplasm.²⁷ The incidence of malignancy is highest in submandibular, sublingual, and minor salivary glands. There are numerous primary salivary gland malignancies, such as mucoepidermoid carcinoma, adenocarcinoma, and adenoid cystic carcinoma. Facial skin SCC may metastasize to periparotid nodes. There are also multiple nonneoplastic causes of salivary gland inflammation. Recurrent diffuse, painful gland enlargement may be suggestive of recurrent sialadenitis and may be
secondary to a stone or xerostomia associated with dehydration or use of diuretics, antidepressants, or lithium. Multiple lymphoepithelial cysts may be associated with HIV and do not require resection.²⁸

Management

After taking a thorough history and performing a physical examination, the physician evaluating a patient for HNC should proceed with diagnostic testing followed by referral to a specialist.

Diagnostic Testing
Laboratory values. Although laboratory values are unlikely to help in evaluation of a malignancy, elevated white blood cell count, erythrocyte sedimentation
rate, and C-reactive protein level are markers of a general inflammatory process that may support a clinically suspected diagnosis of infection. Values that decrease over time may represent progress toward disease resolution.²⁹

Imaging. If malignancy is suspected, imaging should be obtained. Imaging has an important role in corroborating examination findings of a mass. Imaging
also provides an accurate baseline assessment of tumor size and extent. Recommended imaging modalities include:

• Ultrasonography (US). This quick and inexpensive modality can be used to visualize suspicious neck lesions. It is helpful in performing real-time assessments and differentiating cysts from solid masses and abscesses from reactive lymph nodes or infiltrative tumors. Challenges with US include its inability to penetrate bone and practitioners’ variable interpretation of images. A different modality invariably is needed to document location and spread of suspected HNC.
• MRI and CT. These are necessary for HNC evaluation and staging. Generally, they are equivalent in node assessment, but MRI is preferable in tongue and pharynx evaluation, and CT is preferable in the larynx. An ideal image should extend from the skull base to the clavicles, demonstrating the extent of the primary tumor and potential metastases to the neck nodes. As MRI is best protocoled by an experienced head and neck radiologist, it is preferable to refer the patient to such a specialist and allow Oto-HNS to arrange the imaging. Contraindications to MRI include pacemakers and shrapnel (common among veteran patients) and claustrophobia (common among patients with PTSD).
• PET-CT. This modality helps in staging, detecting distant metastases, assessing treatment response after chemoradiation, and locating the primary cancer when a proven neck metastasis has no obvious source. Whether PET-CT should be performed before initial referral should be discussed with the specialist. A case with a proven distant metastasis likely is not operable and would be better served with a referral to medical oncology.

Biopsy. For almost all HNCs, the initial biopsy modality should be FNA. Although intraoral lesions may benefit from incisional biopsy, this procedure should not delay triage and may be outside the scope of practice for many GPs. A GP can arrange for FNA to be performed before the referral appointment. This modality has excellent diagnostic sensitivity and specificity.^30,31 In the setting of equivocal or negative results despite a high index of suspicion, having a more experienced cytopathologist repeat the FNA is often warranted. Excisional biopsy may be warranted if FNA is nondiagnostic or lymphoma is diagnosed.

Other Interventions

In some cases, the GP has additional important roles— in preparing the patient for the possibility of surgery, treating related conditions, helping the patient cope with this new medical challenge, improving nutrition, and promoting cessation of alcohol drinking and tobacco smoking.

Surgery. For patients with biopsy-proven HNC, preoperative assessment by the GP helps provide clearance for surgery, reduces time to treatment, and lessens the likelihood of postoperative complications. A recent study found that VA patients aged ≥ 70 years had a 30-day postoperative mortality rate of 6% and at least a ≥ 20% risk for a major complication during their hospital stay.³² Given these risks and the overall higher rate of chronic diseases among veterans, the authors recommend preoperative evaluation of comorbidities with particular emphasis on cardiac, renal, and pulmonary status. In addition, specific examinations (eg, electrocardiogram, chest radiograph, basic laboratory tests, liver profile test) are recommended for patients with a history of alcohol abuse.

Malnutrition. At initial diagnosis, many patients with HNC have significant weight loss.33 Unfortunately, the required complex treatment modalities increase malnutrition rates and decrease quality of life.³⁴ Preventive strategies are, therefore, key in improving patients’ overall health. The authors recommend that GPs consider early nutritional consultations and as-needed speech therapy evaluations to provide preventive strategies and exercises to maintain proper swallowing function.³⁵ Patients who are unable to eat because of aspiration caused by a large tumor should be admitted for preoperative gastric tube placement to improve nutrition and, ultimately, surgical outcome. A large percentage of veterans with HNC also have depression, which may lead to decreased appetite.³⁶ Mental health consultations can help in these circumstances, as can use of mirtazapine, which increases appetite and treats depression-related symptoms.

Pain. Nonsteroidal anti-inflammatory drugs (NSAIDs) can be recommended for relief of uncontrolled mild to moderate pain, but they must be discontinued 1 week before surgery to reduce the risk for bleeding complications. The NSAIDs should be avoided entirely in patients with untreated friable tumors of the aerodigestive tract. In patients with biopsy-proven cancer, pain control can involve opiates per World Health Organization guidelines.³⁷ Patients with head and neck SCC often have neuropathic pain, which is more effectively treated with gabapentin.

Alcohol drinking and tobacco smoking. Promoting cessation of these habits is essential for all patients, including those already diagnosed with cancer. Encouraging cessation as well as overall healthy lifestyle choices can reduce cancer risk and improve overall health—and may be the single most efficacious intervention a physician can offer.

Referral

Most patients with suspected HNC should be referred to Oto-HNS. In cases in which lymphoma is most highly suspected, medical oncology is the most appropriate initial referral. Early dental consultation is also necessary if an obturator will be needed (eg, as with a hard palate malignancy) or if irradiation is planned (radiation-induced xerostomia significantly increases the risk for dental caries).³⁸ For all new cancer diagnoses, the GP can contact the Oto-HNS specialist for help in tailoring the patient evaluation to the practices and resources at the GP’s home institution and reduce time to treatment.

Conclusion

General practitioners are essential in identifying and triaging veterans with HNC. High-risk patients with a growing mass require proper assessment, including a thorough history and physical examination, FNA for diagnosis, and appropriate specialist referral. Although this article provides a helpful framework for thinking about patients with HNC, the authors encourage GPs to check the National Comprehensive Cancer Network guidelines for additional information on the topics covered here. With this knowledge, GPs can improve outcomes for veterans with HNC.

Author disclosures
The authors report no actual or potential conflicts of interest with regard to this article.

Disclaimer
The opinions expressed herein are those of the authors and do not necessarily reflect those of Federal Practitioner, Frontline Medical Communications Inc., the U.S. Government, or any of its agencies. This article may discuss unlabeled or investigational use of certain drugs. Please review complete prescribing information for specific drugs or drug combinations—including indications, contraindications, warnings, and adverse effects—before administering pharmacologic therapy to patients.

Click here to read the digital edition.

High-risk patients with a growing mass require proper assessment, including a thorough history, physical examination, and fine-needle aspiration for diagnosis.

A 65-year-old Vietnam veteran with a history of posttraumatic stress disorder (PTSD), transient ischemic attack, alcohol dependence, and a smoking history of 50 pack-years presents with a neck mass that has been growing for 2 months and unintentional weight loss of 25 pounds over 6 months. What is the differential diagnosis? How does a general practitioner evaluate, manage, and efficiently triage this patient?

Such cases, in which a head and neck cancer (HNC) diagnosis is suspected, can be unnerving for both physician and patient. However, knowledgeable general practitioners (GPs) can play a pivotal role in recognizing high-risk patients, initiating workups, and referring to appropriate specialists, resulting in earlier detection and potentially better outcomes.

This article outlines the authors’ recommended best practices for GPs treating patients with presumed HNC. Although the focus here is on the veteran population, in which HNC rates are significantly higher, many of the suggestions presented are applicable to the general population.

Background

Head and neck cancers represent a diverse family of malignancies of the nasopharynx, oropharynx, hypopharynx, larynx, oral cavity, paranasal sinuses, and salivary glands. This article does not cover thyroid, ophthalmologic, neurologic, or skin malignancies. The yearly worldwide incidence of all HNC cases is more than 550,000.¹ In the U.S., 55,000 new HNC cases, representing 3% of all new malignancies, are reported annually. The 5-year survival rate is 60%, but 12,000 Americans die each year of head and neck cancer.² Most HNCs occur in males aged ≥ 50 years, and the incidence increases with age. Almost $3.6 billion is spent treating HNC in the U.S. annually.³

Risk Factors

Alcohol and tobacco consumption strongly predisposes patients to squamous cell carcinoma (SCC), which accounts for 90% of HNCs. Together, alcohol and tobacco act multiplicatively.^4,5 For instance, heavy drinkers (≥ 10 drinks daily) are at 5-fold increased risk for oral and pharyngeal cancers, heavy smokers (≥ 1 pack daily) are at 20-fold increased risk, and people who both drink and smoke heavily are at 50-fold increased risk.⁶ Head and neck cancer rates are significantly elevated even for moderate/light drinkers and smokers.

Veterans have disproportionately high rates of alcohol drinking and tobacco smoking,^7,8 in part because these habits are ingrained in military culture. During World Wars I and II, tobacco companies supplied soldiers with daily rations of cigarettes,⁹ and advertisers targeted military personnel by linking smoking with patriotism, strength, and toughness.¹⁰ The VHA and the DoD reported that 33% of veterans and active-duty service personnel smoke—compared with 23% of civilians.¹¹ Vietnam veterans, 47% of whom smoke, are at particular risk for HNC.¹²

Cessation of alcohol drinking and tobacco smoking is essential for overall prognosis, especially after HNC has been diagnosed. Continued smoking after HNC treatment increases the recurrence rate 4-fold.¹³ There also is mounting evidence that cessation of drinking and smoking can reverse the risk for HNC over time. According to a meta-analysis, quitting smoking for just 1 year begins to lower the risk for HNC. Quitting smoking for 20 years reduces the risk to the level of never smokers, and abstaining from alcohol for 20 years decreases the risk by nearly 40%.¹⁴

Viral infections are risk factors for development of oral cavity, oropharyngeal, laryngeal, and nasopharyngeal carcinoma (NPC). Sixty percent of oropharyngeal cancers are positive for human papillomavirus (HPV) infection,¹⁵ and most NPCs are associated with prior Epstein-Barr virus (EBV) exposure, particularly in populations from southern China, Southeast Asia, North Africa, and the Middle East.¹⁶

Evaluation

Workup of a possible HNC starts with taking a thorough history. Early HNC symptoms that may prompt a patient to seek medical care include neck mass, nonhealing oral ulcer, voice change, sore throat for more than 2 weeks, ear pain, nasal obstruction, serous otitis media, dysphagia, and odynophagia. Patients with advanced HNC may present with unintentional weight loss, decreased appetite, and cranial nerve deficits. For alcohol or tobacco users who present with any of the symptoms, SCC should lead the differential diagnosis, prompting examination of the head and neck. The authors present a general outline for performing this examination and detail the most common types of HNC encountered in the GP setting.

Physical Examination

The GP should perform a bimanual examination of the oral cavity, ears, nose, thyroid, and cranial nerve function with the help of a headlight. The physician should use 2 tongue blades to explore the oral cavity and palpate for suspicious oral lesions. It is often possible to feel a lesion before visualizing it on the base of the tongue. If there is a presenting mass, the physician should document the mass site, size, shape, consistency, tenderness, mobility, and accompanying deficits or symptoms.

Also recommended is a thorough examination of the facial, submandibular, and other cervical lymph nodes. The drainage patterns of these nodes can help the GP track potential routes of malignant infiltration. The submental and submandibular lymph nodes (level 1) drain the lower lip, floor of mouth, anterior tongue, and side of nose. The nodes along the mid and internal jugular vein (levels 2-4) and between the sternocleidomastoid and trapezius muscles (level 5) drain the oropharynx, mid tongue, larynx, hypopharynx, parotid gland, and skin of the face and ear. Nontender hard nodes are more likely to be malignant, as are nodes of the posterior triangle (level 5).¹⁷

Malignancy by Site

Oral cavity. The oral cavity includes the lips, buccal mucosa, teeth, gums, anterior two-thirds of tongue, floor of mouth, alveolar ridge, retromolar trigone, and hard palate. The oral cavity is the most common site for HNCs.¹⁸ The most common symptoms of malignancy of the oral cavity include dysphonia, nonhealing oral ulcers, loose teeth, bleeding, change in denture fit, and chin numbness, which could indicate mandibular invasion with inferior alveolar nerve involvement.¹⁹

For thorough assessment of the oral cavity, the patient should remove all temporary dental appliances. Then, with a tongue blade in each hand, the physician should thoroughly examine the oral mucosa, moving the tongue laterally to evaluate the floor of mouth, and palpate the mucosal surfaces to identify submucosal cancers in the posterior tongue and floor of mouth. Minor salivary glands are ubiquitous in the oral cavity and may be involved by cancer. Ulcerated painful lesions that last longer than 2 weeks are less likely to be common viral or aphthous ulcers. For either an oral cavity mass or a nonhealing ulcer that persists more than 4 weeks, malignancy should be suspected, and the patient should be referred for imaging and biopsy.

Leukoplakias are white patches in the oral cavity that develop from squamous epithelial hyperplasia and cannot be scraped away with a tonghpvue blade. The lesions are usually benign, but, if there is an element of redness (erythroplakia), the risk for harboring dysplasia is much higher, though the differential diagnosis includes trauma from adjacent teeth or lichen planus. If leukoplakia is seen, the physician should accurately note the size, location, and site and should monitor every 3 to 4 months. If erythroplakia, enlargement of leukoplakia, or any evidence of mucosal invasion is noted, the physician should refer to otolaryngologyhead and neck surgery (Oto-HNS). The authors advise against lasering leukoplakia; it is unnecessary, can make subsequent evaluation more difficult, and can mask recurrent malignancy.

Oropharynx. The oropharynx includes the posterior third of tongue, soft palate, palatine and lingual tonsils, and the posterior and lateral pharyngeal walls superior to tip of epiglottis. Cancers can arise in any of these locations and may present with dysphagia, odynophagia, referred
otalgia, hoarseness, and enlarged lymph nodes. In advanced cases, there may be bleeding, airway obstruction, and aspiration. Nonsmokers with oropharyngeal SCC are likely to be HPV positive and may be younger than the typical patient with alcohol- or tobacco-related HNC. Human papillomavirus positive oropharyngeal carcinoma has a much better prognosis than its tobaccorelated counterpart does. Physical examination should include assessment of tonsillar size and symmetry, palpation of neck lymph nodes, and palpation of base of tongue. Treatment may involve surgery, radiation, or chemoradiation, depending on factors such as extent of disease and comorbidities.

Nasopharynx. The nasopharynx extends from the nasal cavity (posterior to nasal septum) to the oropharynx. The most common NPC symptoms are middle-ear effusion and enlarged neck nodes. Nasal obstruction, epistaxis, or cranial nerve deficits also may occur. The nasopharynx
is best assessed with a fiberoptic scope. Most NPCs are associated with EBV infection, and viral levels can be used to monitor response to treatment.20 Early biopsy is indicated if a nasopharyngeal mass is found.

Larynx. As with the nasopharynx, the larynx is best seen with a fiberoptic scope. Malignancy generally presents with hoarseness, voice changes, cough, sore throat, or, if more advanced, airway compromise such as stridor and neck adenopathy. As larynx HNCs may be associated
with aspiration, the authors recommend asking “Does food go down the wrong pipe?” or “Do you cough when you eat?” and having the patient drink and document any difficulty. A smoker with hoarseness lasting more than 2 weeks should be referred to Oto-HNS for endoscopic assessment. Among veterans, other causes of hoarseness include polyps,Candida infection associated with inhalation of steroids for chronic obstructive pulmonary disease, and recurrent nerve paralysis from thyroid or lung cancer.

Neck. Patients with HNCs commonly present with a neck mass. Fifty percent to 80% of adults with a nontender neck mass are harboring a malignancy.^21,22 In a patient without HIV, a neck mass larger than 2 cm should be evaluated for cancer, especially if the mass is hard and nontender.²³ Computed tomography (CT) is recommended for initial evaluation, which, if there is FNA confirmed carcinoma, should be followed by positron emission tomography (PET). If there is concern for parotidor skull base tumors, magnetic resonance imaging (MRI) is preferable for demonstrating soft-tissue definition and disease extent.

If the patient is aged < 40 years and lymph nodes have been present for less than 2 to 4 weeks, are tender, or are associated with fever or poor dental hygiene, then an infection may instead be the cause. Dentistry referral and/or an antibiotic trial should be considered. Lymphomas, also common in the neck, may be accompanied by “B symptoms” (fever, night sweats, unintentional weight loss of > 10%).²⁴ If lymphoma is suspected, fine-needle aspiration (FNA) for cytology and flow cytometry should be performed. If lymphoma is confirmed, the GP should refer the patient to an appropriate medical oncologist for further evaluation, which may include referral to Oto-HNS for core or open biopsy. Contraindications to FNA of a neck mass include paragangliomas, such as a carotid body tumor.

Other cancers of the upper aerodigestive tract also often spread to the neck nodes and may initially present as a neck mass. A thorough examination can usually point to the primary cancer, and FNA will provide the diagnosis with high specificity and sensitivity.²⁵ Midline cystic neck masses in close proximity to the hyoid bone are likely thyroglossal duct cysts. If these cysts grow, they likely require removal.

Salivary glands. The submandibular, sublingual, and parotid are the major salivary glands. There also are hundreds of small salivary glands scattered through the oral and pharyngeal mucosa. Tumors arising from the salivary glands represent about 6% of all head and neck masses; these tumors are nearly 3 times more common in men than in women.²⁶ About 80% of salivary gland tumors originate in the parotid gland; patients with such tumors typically present with a painless parotid mass.²⁶ In advanced cases, patients may present with skin infiltration and facial paralysis secondary to involvement of
the facial nerve that courses through the parotid gland after it exits the temporal bone near the mastoid tip.

Salivary gland tumors are most commonly benign, and pleomorphic adenomas are the most common benign parotid neoplasm.²⁷ The incidence of malignancy is highest in submandibular, sublingual, and minor salivary glands. There are numerous primary salivary gland malignancies, such as mucoepidermoid carcinoma, adenocarcinoma, and adenoid cystic carcinoma. Facial skin SCC may metastasize to periparotid nodes. There are also multiple nonneoplastic causes of salivary gland inflammation. Recurrent diffuse, painful gland enlargement may be suggestive of recurrent sialadenitis and may be
secondary to a stone or xerostomia associated with dehydration or use of diuretics, antidepressants, or lithium. Multiple lymphoepithelial cysts may be associated with HIV and do not require resection.²⁸

Management

After taking a thorough history and performing a physical examination, the physician evaluating a patient for HNC should proceed with diagnostic testing followed by referral to a specialist.

Diagnostic Testing
Laboratory values. Although laboratory values are unlikely to help in evaluation of a malignancy, elevated white blood cell count, erythrocyte sedimentation
rate, and C-reactive protein level are markers of a general inflammatory process that may support a clinically suspected diagnosis of infection. Values that decrease over time may represent progress toward disease resolution.²⁹

Imaging. If malignancy is suspected, imaging should be obtained. Imaging has an important role in corroborating examination findings of a mass. Imaging
also provides an accurate baseline assessment of tumor size and extent. Recommended imaging modalities include:

• Ultrasonography (US). This quick and inexpensive modality can be used to visualize suspicious neck lesions. It is helpful in performing real-time assessments and differentiating cysts from solid masses and abscesses from reactive lymph nodes or infiltrative tumors. Challenges with US include its inability to penetrate bone and practitioners’ variable interpretation of images. A different modality invariably is needed to document location and spread of suspected HNC.
• MRI and CT. These are necessary for HNC evaluation and staging. Generally, they are equivalent in node assessment, but MRI is preferable in tongue and pharynx evaluation, and CT is preferable in the larynx. An ideal image should extend from the skull base to the clavicles, demonstrating the extent of the primary tumor and potential metastases to the neck nodes. As MRI is best protocoled by an experienced head and neck radiologist, it is preferable to refer the patient to such a specialist and allow Oto-HNS to arrange the imaging. Contraindications to MRI include pacemakers and shrapnel (common among veteran patients) and claustrophobia (common among patients with PTSD).
• PET-CT. This modality helps in staging, detecting distant metastases, assessing treatment response after chemoradiation, and locating the primary cancer when a proven neck metastasis has no obvious source. Whether PET-CT should be performed before initial referral should be discussed with the specialist. A case with a proven distant metastasis likely is not operable and would be better served with a referral to medical oncology.

Biopsy. For almost all HNCs, the initial biopsy modality should be FNA. Although intraoral lesions may benefit from incisional biopsy, this procedure should not delay triage and may be outside the scope of practice for many GPs. A GP can arrange for FNA to be performed before the referral appointment. This modality has excellent diagnostic sensitivity and specificity.^30,31 In the setting of equivocal or negative results despite a high index of suspicion, having a more experienced cytopathologist repeat the FNA is often warranted. Excisional biopsy may be warranted if FNA is nondiagnostic or lymphoma is diagnosed.

Other Interventions

In some cases, the GP has additional important roles— in preparing the patient for the possibility of surgery, treating related conditions, helping the patient cope with this new medical challenge, improving nutrition, and promoting cessation of alcohol drinking and tobacco smoking.

Surgery. For patients with biopsy-proven HNC, preoperative assessment by the GP helps provide clearance for surgery, reduces time to treatment, and lessens the likelihood of postoperative complications. A recent study found that VA patients aged ≥ 70 years had a 30-day postoperative mortality rate of 6% and at least a ≥ 20% risk for a major complication during their hospital stay.³² Given these risks and the overall higher rate of chronic diseases among veterans, the authors recommend preoperative evaluation of comorbidities with particular emphasis on cardiac, renal, and pulmonary status. In addition, specific examinations (eg, electrocardiogram, chest radiograph, basic laboratory tests, liver profile test) are recommended for patients with a history of alcohol abuse.

Malnutrition. At initial diagnosis, many patients with HNC have significant weight loss.33 Unfortunately, the required complex treatment modalities increase malnutrition rates and decrease quality of life.³⁴ Preventive strategies are, therefore, key in improving patients’ overall health. The authors recommend that GPs consider early nutritional consultations and as-needed speech therapy evaluations to provide preventive strategies and exercises to maintain proper swallowing function.³⁵ Patients who are unable to eat because of aspiration caused by a large tumor should be admitted for preoperative gastric tube placement to improve nutrition and, ultimately, surgical outcome. A large percentage of veterans with HNC also have depression, which may lead to decreased appetite.³⁶ Mental health consultations can help in these circumstances, as can use of mirtazapine, which increases appetite and treats depression-related symptoms.

Pain. Nonsteroidal anti-inflammatory drugs (NSAIDs) can be recommended for relief of uncontrolled mild to moderate pain, but they must be discontinued 1 week before surgery to reduce the risk for bleeding complications. The NSAIDs should be avoided entirely in patients with untreated friable tumors of the aerodigestive tract. In patients with biopsy-proven cancer, pain control can involve opiates per World Health Organization guidelines.³⁷ Patients with head and neck SCC often have neuropathic pain, which is more effectively treated with gabapentin.

Alcohol drinking and tobacco smoking. Promoting cessation of these habits is essential for all patients, including those already diagnosed with cancer. Encouraging cessation as well as overall healthy lifestyle choices can reduce cancer risk and improve overall health—and may be the single most efficacious intervention a physician can offer.

Referral

Most patients with suspected HNC should be referred to Oto-HNS. In cases in which lymphoma is most highly suspected, medical oncology is the most appropriate initial referral. Early dental consultation is also necessary if an obturator will be needed (eg, as with a hard palate malignancy) or if irradiation is planned (radiation-induced xerostomia significantly increases the risk for dental caries).³⁸ For all new cancer diagnoses, the GP can contact the Oto-HNS specialist for help in tailoring the patient evaluation to the practices and resources at the GP’s home institution and reduce time to treatment.

Conclusion

General practitioners are essential in identifying and triaging veterans with HNC. High-risk patients with a growing mass require proper assessment, including a thorough history and physical examination, FNA for diagnosis, and appropriate specialist referral. Although this article provides a helpful framework for thinking about patients with HNC, the authors encourage GPs to check the National Comprehensive Cancer Network guidelines for additional information on the topics covered here. With this knowledge, GPs can improve outcomes for veterans with HNC.

Author disclosures
The authors report no actual or potential conflicts of interest with regard to this article.

Disclaimer
The opinions expressed herein are those of the authors and do not necessarily reflect those of Federal Practitioner, Frontline Medical Communications Inc., the U.S. Government, or any of its agencies. This article may discuss unlabeled or investigational use of certain drugs. Please review complete prescribing information for specific drugs or drug combinations—including indications, contraindications, warnings, and adverse effects—before administering pharmacologic therapy to patients.

Click here to read the digital edition.