In HPV-Positive Head and Neck Cancer, Treatment Is a Quandary

The topic of head and neck cancer is especially timely since the disease is evolving. A hematologist/oncologist with the Association of VA Hematology/Oncology (AVAHO) told colleagues that specialists are grappling with how to de-escalate treatment.

Molly Tokaz, MD, of Veterans Affairs Puget Sound Health Care and the University of Washington said tobacco is fading as a cause as fewer people smoke, and that human papillomavirus (HPV) is triggering more cases. HPV-positive patients have better prognoses, raising the prospect that their treatment could be adjusted.

“Instead of increasing the amount of therapy we're giving, we’re trying to peel it back,” she said. “If they’re going to respond no matter what we do, why are we going in with these huge weapons of mass destruction if we can get the same results with something more like a light infantry?”

Tokaz spoke about deescalating therapy at a May 2024 regional AVAHO meeting in Seattle that was focused on head and neck cancer. She elaborated on her presentation in an interview with Federal Practitioner. according to Tokaz, 90% of head and neck cancers are mucosal squamous cell carcinomas (SCC). HPV is associated specifically with nasopharyngeal cancer, which is distinct from SCC, and oropharyngeal cancer, which has been linked to better prognoses.

HPV-positive head and neck cancer is a unique entity with its own epidemiology, clinical prognosis, and treatment. “Patients tend to be younger without the same number of comorbid conditions,” Tokaz said. “Some of them are never smokers or light smokers. So, it's a different demographic than we’ve seen traditionally.”

The bad news is that HPV-associated head and neck cancer numbers are on the rise. Fortunately, outcomes tend to be better for the HPV-positive forms.

As for therapy for head and neck cancer, immunotherapy and targeted therapy play smaller roles than in some other cancers because the form tends to be diagnosed in early stages before metastases appear. Surgery, chemotherapy, and radiation remain the major treatments. According to Tokaz’s presentation, surgery, or radiation—often with minimal adjuvant chemotherapy—can be appropriate for the earliest stage I and II cases of head and neck SCC. (She noted that HPV-positive oropharyngeal squamous cell carcinoma has its own staging system.)

Stage I and II cases make up 15% of new diagnoses and have a 5-year survival rate of > 70%. “In the earliest days, our main role was to make radiation work better and reduce it while adding a minimum amount of toxicity mutations,” she said. “Chemotherapy can help, but it’s only demonstrated improvement in overall survival in patients with positive surgical margins and extracapsular extension.”

In Stage III, IVA, and IVB cases, which make up 70% of new diagnoses, chemotherapy plus radiation is recommended. Five-year survival drops to 30% to 50%. Finally, 10% of new diagnoses are Stage IVC, which is incurable and median survival is < 1 year.

Since HPV-positive patients generally have better prognoses, oncologists are considering how to adjust their treatment. However, Tokaz notes that clinical trials have not shown a benefit from less intensive treatment in these patients. “At this point, we still treat them the same way as HPV-negative patients. But it's an ongoing area of research.”

Researchers are also exploring how to optimize regimens in patients ineligible for treatment with the chemotherapy agent cisplatin. “These folks have been traditionally excluded from clinical trials because they’re sicker,” Tokaz explained. “Researchers normally want the fittest and the best patients [in trials]. If you give a drug to someone with a lot of other comorbid conditions, they might not do as well with it, and it makes your drug look bad.”

Figuring out how to treat these patients is an especially urgent task in head and neck cancer because so many patients are frail and have comorbidities. More globally, Tokaz said the rise of HPV-related head and neck cancer highlights the importance of HPV vaccination, which is crucial for preventing cervical and anal cancer in addition to head and neck cancer. “HPV vaccination for children and young adults is crucial.”

Molly Tokaz, MD, reported no relevant financial relationships.

The topic of head and neck cancer is especially timely since the disease is evolving. A hematologist/oncologist with the Association of VA Hematology/Oncology (AVAHO) told colleagues that specialists are grappling with how to de-escalate treatment.

Molly Tokaz, MD, of Veterans Affairs Puget Sound Health Care and the University of Washington said tobacco is fading as a cause as fewer people smoke, and that human papillomavirus (HPV) is triggering more cases. HPV-positive patients have better prognoses, raising the prospect that their treatment could be adjusted.

“Instead of increasing the amount of therapy we're giving, we’re trying to peel it back,” she said. “If they’re going to respond no matter what we do, why are we going in with these huge weapons of mass destruction if we can get the same results with something more like a light infantry?”

Tokaz spoke about deescalating therapy at a May 2024 regional AVAHO meeting in Seattle that was focused on head and neck cancer. She elaborated on her presentation in an interview with Federal Practitioner. according to Tokaz, 90% of head and neck cancers are mucosal squamous cell carcinomas (SCC). HPV is associated specifically with nasopharyngeal cancer, which is distinct from SCC, and oropharyngeal cancer, which has been linked to better prognoses.

HPV-positive head and neck cancer is a unique entity with its own epidemiology, clinical prognosis, and treatment. “Patients tend to be younger without the same number of comorbid conditions,” Tokaz said. “Some of them are never smokers or light smokers. So, it's a different demographic than we’ve seen traditionally.”

The bad news is that HPV-associated head and neck cancer numbers are on the rise. Fortunately, outcomes tend to be better for the HPV-positive forms.

As for therapy for head and neck cancer, immunotherapy and targeted therapy play smaller roles than in some other cancers because the form tends to be diagnosed in early stages before metastases appear. Surgery, chemotherapy, and radiation remain the major treatments. According to Tokaz’s presentation, surgery, or radiation—often with minimal adjuvant chemotherapy—can be appropriate for the earliest stage I and II cases of head and neck SCC. (She noted that HPV-positive oropharyngeal squamous cell carcinoma has its own staging system.)

Stage I and II cases make up 15% of new diagnoses and have a 5-year survival rate of > 70%. “In the earliest days, our main role was to make radiation work better and reduce it while adding a minimum amount of toxicity mutations,” she said. “Chemotherapy can help, but it’s only demonstrated improvement in overall survival in patients with positive surgical margins and extracapsular extension.”

In Stage III, IVA, and IVB cases, which make up 70% of new diagnoses, chemotherapy plus radiation is recommended. Five-year survival drops to 30% to 50%. Finally, 10% of new diagnoses are Stage IVC, which is incurable and median survival is < 1 year.

Since HPV-positive patients generally have better prognoses, oncologists are considering how to adjust their treatment. However, Tokaz notes that clinical trials have not shown a benefit from less intensive treatment in these patients. “At this point, we still treat them the same way as HPV-negative patients. But it's an ongoing area of research.”

Researchers are also exploring how to optimize regimens in patients ineligible for treatment with the chemotherapy agent cisplatin. “These folks have been traditionally excluded from clinical trials because they’re sicker,” Tokaz explained. “Researchers normally want the fittest and the best patients [in trials]. If you give a drug to someone with a lot of other comorbid conditions, they might not do as well with it, and it makes your drug look bad.”

Figuring out how to treat these patients is an especially urgent task in head and neck cancer because so many patients are frail and have comorbidities. More globally, Tokaz said the rise of HPV-related head and neck cancer highlights the importance of HPV vaccination, which is crucial for preventing cervical and anal cancer in addition to head and neck cancer. “HPV vaccination for children and young adults is crucial.”

Molly Tokaz, MD, reported no relevant financial relationships.

The topic of head and neck cancer is especially timely since the disease is evolving. A hematologist/oncologist with the Association of VA Hematology/Oncology (AVAHO) told colleagues that specialists are grappling with how to de-escalate treatment.

Molly Tokaz, MD, of Veterans Affairs Puget Sound Health Care and the University of Washington said tobacco is fading as a cause as fewer people smoke, and that human papillomavirus (HPV) is triggering more cases. HPV-positive patients have better prognoses, raising the prospect that their treatment could be adjusted.

“Instead of increasing the amount of therapy we're giving, we’re trying to peel it back,” she said. “If they’re going to respond no matter what we do, why are we going in with these huge weapons of mass destruction if we can get the same results with something more like a light infantry?”

Tokaz spoke about deescalating therapy at a May 2024 regional AVAHO meeting in Seattle that was focused on head and neck cancer. She elaborated on her presentation in an interview with Federal Practitioner. according to Tokaz, 90% of head and neck cancers are mucosal squamous cell carcinomas (SCC). HPV is associated specifically with nasopharyngeal cancer, which is distinct from SCC, and oropharyngeal cancer, which has been linked to better prognoses.

HPV-positive head and neck cancer is a unique entity with its own epidemiology, clinical prognosis, and treatment. “Patients tend to be younger without the same number of comorbid conditions,” Tokaz said. “Some of them are never smokers or light smokers. So, it's a different demographic than we’ve seen traditionally.”

The bad news is that HPV-associated head and neck cancer numbers are on the rise. Fortunately, outcomes tend to be better for the HPV-positive forms.

As for therapy for head and neck cancer, immunotherapy and targeted therapy play smaller roles than in some other cancers because the form tends to be diagnosed in early stages before metastases appear. Surgery, chemotherapy, and radiation remain the major treatments. According to Tokaz’s presentation, surgery, or radiation—often with minimal adjuvant chemotherapy—can be appropriate for the earliest stage I and II cases of head and neck SCC. (She noted that HPV-positive oropharyngeal squamous cell carcinoma has its own staging system.)

Stage I and II cases make up 15% of new diagnoses and have a 5-year survival rate of > 70%. “In the earliest days, our main role was to make radiation work better and reduce it while adding a minimum amount of toxicity mutations,” she said. “Chemotherapy can help, but it’s only demonstrated improvement in overall survival in patients with positive surgical margins and extracapsular extension.”

In Stage III, IVA, and IVB cases, which make up 70% of new diagnoses, chemotherapy plus radiation is recommended. Five-year survival drops to 30% to 50%. Finally, 10% of new diagnoses are Stage IVC, which is incurable and median survival is < 1 year.

Since HPV-positive patients generally have better prognoses, oncologists are considering how to adjust their treatment. However, Tokaz notes that clinical trials have not shown a benefit from less intensive treatment in these patients. “At this point, we still treat them the same way as HPV-negative patients. But it's an ongoing area of research.”

Researchers are also exploring how to optimize regimens in patients ineligible for treatment with the chemotherapy agent cisplatin. “These folks have been traditionally excluded from clinical trials because they’re sicker,” Tokaz explained. “Researchers normally want the fittest and the best patients [in trials]. If you give a drug to someone with a lot of other comorbid conditions, they might not do as well with it, and it makes your drug look bad.”

Figuring out how to treat these patients is an especially urgent task in head and neck cancer because so many patients are frail and have comorbidities. More globally, Tokaz said the rise of HPV-related head and neck cancer highlights the importance of HPV vaccination, which is crucial for preventing cervical and anal cancer in addition to head and neck cancer. “HPV vaccination for children and young adults is crucial.”

Molly Tokaz, MD, reported no relevant financial relationships.