The first 60 days: HPV-negative head and neck squamous cell carcinoma (including HPV-negative oropharyngeal cancer)
Head and neck cancers caused by tobacco and alcohol rather than HPV are harder to cure: surgery or cisplatin chemoradiation is the mainstay, immunotherapy given around surgery (KEYNOTE-689) or after it (NIVOPOSTOP) has begun to help, and pembrolizumab is the first treatment once the disease has spread. Below, week by week, is what OnCo's record of HPV-negative head and neck squamous cell carcinoma (including HPV-negative oropharyngeal cancer) says about the first two months: the order is typical, the timing is yours to ask about. Sections appear only where the record has something to say. Orientation, not medical advice.
What happens now
Staging tests establish exactly what and where the cancer is. Everything else follows from the answers.
Biopsy with p16 (and HPV testing for oropharyngeal primaries), PD-L1 combined positive score, panendoscopy for second primaries, CT or MRI and PET-CT for stage III to IV.
Ask which of these were tested and what the results were; see the report reader for what each value means.
These specialties appear in the standard of care for this cancer. In most centres they meet weekly as a tumour board to agree each plan; you can ask when yours was discussed and what was decided.
- PathologistNamed in the standard of care for: Diagnosis and staging, Resectable stage III to IVA.
- RadiologistNamed in the standard of care for: Diagnosis and staging.
- SurgeonNamed in the standard of care for: Resectable stage III to IVA.
- Medical oncologistNamed in the standard of care for: Resectable stage III to IVA, After surgery, high risk, Unresectable or organ-preserving, Recurrent or metastatic and 1 more.
- Clinical oncologist (radiotherapy)Named in the standard of care for: Resectable stage III to IVA, After surgery, high risk, Unresectable or organ-preserving.
- Palliative and supportive care teamNamed in the standard of care for: Prevention.
A second opinion from a centre that treats many similar cases is normal, not rude; the standard of care tells you what to compare it against.
Each row is a setting from the standard of care, in the order it usually arises. Not all will apply to you; your stage and biomarkers decide which do. The guideline grade, where recorded, says how strong the evidence is.
Smoking cessation, alcohol reduction and betel quid cessation; second primaries make cessation after diagnosis worthwhile.
Oral metronomic methotrexate with celecoxib, with or without low-dose nivolumab (Tata Memorial trials).
Surgery with neck dissection; perioperative pembrolizumab for tumours with a combined positive score of 1 or more (KEYNOTE-689), then radiotherapy or chemoradiation by pathology.
- 4.After surgery, high riskNCCN category Category 1 (chemoradiation), NCCN Guidelines: Head and Neck Cancers
Postoperative cisplatin chemoradiation for extranodal extension or positive margins; nivolumab added on the basis of NIVOPOSTOP.
Definitive cisplatin chemoradiation to 70 Gy; cetuximab with radiotherapy for patients who cannot have cisplatin (Bonner).
Pembrolizumab alone (combined positive score 1 or more) or with platinum-fluorouracil (KEYNOTE-048); cetuximab-based EXTREME for rapid disease or PD-1 failure.
Generated from this cancer's standard of care, biomarkers and open problems. Take the group that matches where you are. To tick, add your own and print, open the one-page appointment sheet.
Newly diagnosed
- What is my exact diagnosis, stage, and grade, and which tests established them?Everything else follows from an accurate stage and subtype.
- Which biomarkers have been tested on my tumour (for example p16 negative and HPV DNA negative, PD-L1 combined positive score, TP53 mutation and CDKN2A loss, EGFR expression, Extranodal extension and margin status), and what were the results?These results decide eligibility for targeted therapy, immunotherapy, and trials.
- Which subtype is my cancer, and does that change the recommended treatment?Recognised subtypes for this cancer include HPV-negative oropharyngeal cancer, Oral cavity squamous cell carcinoma, Laryngeal and hypopharyngeal squamous cell carcinoma.
- Is germline (inherited) genetic testing recommended for me or my family?Inherited variants can change treatment and matter for relatives.
Diagnosis and staging
- For my situation (diagnosis and staging), which of the standard options do you recommend and why?Guideline options include: Biopsy with p16 (and HPV testing for oropharyngeal primaries), PD-L1 combined positive score, panendoscopy for second primaries, CT or MRI and PET-CT for stage III to IV.
Resectable stage III to IVA
- For my situation (resectable stage iii to iva), which of the standard options do you recommend and why?Guideline options include: Surgery with neck dissection; perioperative pembrolizumab for tumours with a combined positive score of 1 or more (KEYNOTE-689), then radiotherapy or chemoradiation by pathology.
- Am I a candidate for Pembrolizumab, and what side effects should I expect?Knowing the expected toxicities helps you plan work, family, and supportive care.
- How do the results of KEYNOTE-689 apply to someone like me?Trial populations differ from individual patients; ask how closely you match.
After surgery, high risk
- For my situation (after surgery, high risk), which of the standard options do you recommend and why?Guideline options include: Postoperative cisplatin chemoradiation for extranodal extension or positive margins; nivolumab added on the basis of NIVOPOSTOP.
- Am I a candidate for Cisplatin, Nivolumab, and what side effects should I expect?Knowing the expected toxicities helps you plan work, family, and supportive care.
- How do the results of NIVOPOSTOP (GORTEC 2018-01) apply to someone like me?Trial populations differ from individual patients; ask how closely you match.
Unresectable or organ-preserving
- For my situation (unresectable or organ-preserving), which of the standard options do you recommend and why?Guideline options include: Definitive cisplatin chemoradiation to 70 Gy; cetuximab with radiotherapy for patients who cannot have cisplatin (Bonner).
- Am I a candidate for Cisplatin, Cetuximab, and what side effects should I expect?Knowing the expected toxicities helps you plan work, family, and supportive care.
- How do the results of Bonner trial (cetuximab plus radiotherapy) apply to someone like me?Trial populations differ from individual patients; ask how closely you match.
Recurrent or metastatic
- For my situation (recurrent or metastatic), which of the standard options do you recommend and why?Guideline options include: Pembrolizumab alone (combined positive score 1 or more) or with platinum-fluorouracil (KEYNOTE-048); cetuximab-based EXTREME for rapid disease or PD-1 failure.
- Am I a candidate for Pembrolizumab, Cetuximab, and what side effects should I expect?Knowing the expected toxicities helps you plan work, family, and supportive care.
- How do the results of KEYNOTE-048 and EXTREME apply to someone like me?Trial populations differ from individual patients; ask how closely you match.
Resource-limited settings
- For my situation (resource-limited settings), which of the standard options do you recommend and why?Guideline options include: Oral metronomic methotrexate with celecoxib, with or without low-dose nivolumab (Tata Memorial trials).
- Am I a candidate for Methotrexate, and what side effects should I expect?Knowing the expected toxicities helps you plan work, family, and supportive care.
- How do the results of Oral metronomic chemotherapy vs intravenous cisplatin (Tata Memorial) and Low-dose nivolumab plus metronomic chemotherapy (Tata Memorial) apply to someone like me?Trial populations differ from individual patients; ask how closely you match.
Prevention
- For my situation (prevention), which of the standard options do you recommend and why?Guideline options include: Smoking cessation, alcohol reduction and betel quid cessation; second primaries make cessation after diagnosis worthwhile.
Any stage
- Are there clinical trials I could join, for example of Ficerafusp alfa, FORTIFI-HN01, A Study of Ficlatuzumab in Combination With Cetuximab in Participants With Recurrent or Metastatic (R/M) HPV Negative Head and Neck Squamous Cell Carcinoma, A Study of Dostarlimab vs Placebo After Chemoradiation in Adult Participants With Locally Advanced Unresected Head and Neck Squamous Cell Carcinoma?Trials are how the next standard of care is set; asking early keeps options open.
- Would a second opinion at a high-volume centre change anything, and can you help arrange it?Rare or high-stakes decisions benefit from a centre that treats many similar patients.
- What supportive care (symptom control, nutrition, exercise, mental health, financial help) is available from the start?Supportive care improves quality of life and helps patients complete treatment.
- I read that “Cure rates for locally advanced HPV-negative disease have barely moved in twenty years”. How does that affect my plan?Open problems are where trials and second opinions matter most.
- I read that “No predictive biomarker beyond PD-L1, which is imperfect”. How does that affect my plan?Open problems are where trials and second opinions matter most.
Trials open now for this cancer in OnCo, largest phase first. Joining a trial is a decision like any other: ask what the comparison arm is, whether a placebo is used, and what happens if you leave. The cancer page searches ClinicalTrials.gov live for more.
- A Study of Dostarlimab vs Placebo After Chemoradiation in Adult Participants With Locally Advanced Unresected Head and Neck Squamous Cell CarcinomaPhase 3 · recruiting · NCT06256588A Randomized, Double-blind, Placebo-controlled Phase 3 Study to Evaluate Dostarlimab as Sequential Therapy After Chemoradiation in Participants With Locally Advanced Unresected Head and Neck Squamous Cell Carcinoma
- A Study of Ficlatuzumab in Combination With Cetuximab in Participants With Recurrent or Metastatic (R/M) HPV Negative Head and Neck Squamous Cell CarcinomaPhase 3 · recruiting · NCT06064877A Multicenter, Randomized, Double Blind, Placebo - Controlled, Phase 3 Study of Ficlatuzumab in Combination With Cetuximab in Participants With Recurrent or Metastatic (R/M) HPV -Negative Head and Neck Squamous Cell Carcinoma. (FIERCE-HN)
- FORTIFI-HN01Phase 2/3 · recruiting · NCT06788990Untreated PD-L1-positive, HPV-negative recurrent or metastatic HNSCC: ficerafusp alfa + pembrolizumab vs pembrolizumab
Much of what helps in the first weeks is free if you know to ask: testing, helplines, rides and lodging, second opinions, trial travel.
- HPV-negative head and neck squamous cell carcinoma (including HPV-negative oropharyngeal cancer): the full pageHead and neck cancers caused by tobacco and alcohol rather than HPV are harder to cure: surgery or cisplatin chemoradiation is the mainstay, immunotherapy given around surgery (KEYNOTE-689) or after it (NIVOPOSTOP) has begun to help, and pembrolizumab is the first treatment once the disease has spread.
- One-page appointment sheetYour questions, the words you may hear, what to bring, and space for the answers. Print it.
- Treatment sequencingWhich treatment tends to follow which, line by line.
- NavigatorStandard of care for your stage, what you have tried, and trials near you.
- PD-L1 expression testing (22C3, SP142, SP263): A stain on the tumour biopsy that measures how much of the PD-L1 'don't attack me' protein is present, scored as a tumour proportion or combined positive score.
- Extranodal extension (ENE): Extranodal extension means cancer in a lymph node has burst through the node's capsule into the surrounding fat; in head and neck cancer it is the single finding after surgery that most often turns radiotherapy into chemoradiotherapy, and in HPV-negative disease it moves the stage up.
- HPV-positive (p16) head and neck cancer: Throat cancers caused by the human papillomavirus, identified by a p16 stain.
- CDKN2A/B homozygous deletion: Losing both copies of the CDKN2A/B genes on chromosome 9p21 removes the cell's main brake on division; in an IDH-mutant glioma it alone makes the tumour grade 4, in mesothelioma and melanoma it marks aggressive disease, and the neighbouring MTAP gene usually goes with it, opening a new drug target.
- Chemoradiation (chemoradiotherapy, CRT): Radiotherapy given at the same time as chemotherapy, which sensitises the cancer to radiation.
Every term links to the glossary.