The first 60 days: HPV-positive oropharyngeal cancer
Throat cancers caused by HPV are usually cured with chemoradiation or robotic surgery, so trials now ask how much treatment can be taken away: swapping cisplatin for cetuximab failed, cutting the radiation dose has worked only after surgery so far, and blood tests for HPV DNA may pick out the patients who can safely have less. Below, week by week, is what OnCo's record of HPV-positive 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.
Fine-needle biopsy of the neck node with p16 staining, HPV confirmation where p16 is equivocal, examination and imaging of the tonsils and tongue base, and PET-CT; staged with the HPV-positive system.
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, Early disease (small primary, limited nodes), De-escalation, Surveillance.
- RadiologistNamed in the standard of care for: Diagnosis and staging, Surveillance.
- SurgeonNamed in the standard of care for: Early disease (small primary, limited nodes).
- Medical oncologistNamed in the standard of care for: Early disease (small primary, limited nodes), Locally advanced disease, De-escalation, Recurrent or metastatic and 1 more.
- Clinical oncologist (radiotherapy)Named in the standard of care for: Early disease (small primary, limited nodes), Locally advanced disease, De-escalation.
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.
HPV vaccination of girls and boys before exposure; catch-up vaccination of men is being argued for.
- 2.Early disease (small primary, limited nodes)NCCN category Category 2A, NCCN Guidelines: Head and Neck Cancers
Transoral robotic surgery with neck dissection and pathology-guided adjuvant radiotherapy (E3311), or radiotherapy alone; choice by expected swallowing and voice.
Cisplatin chemoradiation to 70 Gy; cetuximab only for patients who cannot have cisplatin, since RTOG 1016 and De-ESCALaTE showed it inferior.
Reduced-dose or chemotherapy-free treatment only within a trial; NRG-HN005 showed that lowering the dose in definitive chemoradiation on HPV status alone loses control.
Pembrolizumab alone or with platinum-fluorouracil (KEYNOTE-048); HPV-positive tumours respond at least as well as HPV-negative ones.
Examination and PET-CT at about three months; circulating tumour HPV DNA is emerging as a blood test for recurrence.
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 immunohistochemistry, HPV DNA or E6/E7 RNA in situ hybridisation, Smoking pack-years, Circulating tumour HPV DNA, PD-L1 combined positive score), 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-positive tonsil cancer, HPV-positive base of tongue cancer, Low-riskdisease eligible for de-escalation trials.
- 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: Fine-needle biopsy of the neck node with p16 staining, HPV confirmation where p16 is equivocal, examination and imaging of the tonsils and tongue base, and PET-CT; staged with the HPV-positive system.
Early disease (small primary, limited nodes)
- For my situation (early disease (small primary, limited nodes)), which of the standard options do you recommend and why?Guideline options include: Transoral robotic surgery with neck dissection and pathology-guided adjuvant radiotherapy (E3311), or radiotherapy alone; choice by expected swallowing and voice.
- How do the results of ECOG-ACRIN E3311 apply to someone like me?Trial populations differ from individual patients; ask how closely you match.
Locally advanced disease
- For my situation (locally advanced disease), which of the standard options do you recommend and why?Guideline options include: Cisplatin chemoradiation to 70 Gy; cetuximab only for patients who cannot have cisplatin, since RTOG 1016 and De-ESCALaTE showed it inferior.
- 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 RTOG 1016 and De-ESCALaTE HPV apply to someone like me?Trial populations differ from individual patients; ask how closely you match.
De-escalation
- For my situation (de-escalation), which of the standard options do you recommend and why?Guideline options include: Reduced-dose or chemotherapy-free treatment only within a trial; NRG-HN005 showed that lowering the dose in definitive chemoradiation on HPV status alone loses control.
- How do the results of NRG-HN002 & NRG-HN005 (HPV+ de-escalation) and PATHOS apply to someone like me?Trial populations differ from individual patients; ask how closely you match.
Surveillance
- For my situation (surveillance), which of the standard options do you recommend and why?Guideline options include: Examination and PET-CT at about three months; circulating tumour HPV DNA is emerging as a blood test for recurrence.
Recurrent or metastatic
- For my situation (recurrent or metastatic), which of the standard options do you recommend and why?Guideline options include: Pembrolizumab alone or with platinum-fluorouracil (KEYNOTE-048); HPV-positive tumours respond at least as well as HPV-negative ones.
- 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-048 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: HPV vaccination of girls and boys before exposure; catch-up vaccination of men is being argued for.
- Am I a candidate for Nonavalent HPV vaccine, and what side effects should I expect?Knowing the expected toxicities helps you plan work, family, and supportive care.
Any stage
- Are there clinical trials I could join, for example of Circulating tumour HPV DNA (ctHPV-DNA), PATHOS, NRG-HN002 & NRG-HN005 (HPV+ de-escalation), ctHPV-DNA-adapted de-escalation of chemoradiation?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 “Which patients can safely have less treatment, and by what test”. How does that affect my plan?Open problems are where trials and second opinions matter most.
- I read that “Long-term dry mouth, swallowing difficulty and fibrosis in people cured in their fifties”. 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 Clinical Trial Investigating the Safety, Tolerability, and Therapeutic Effects of BNT113 in Combination With Pembrolizumab Versus Pembrolizumab Alone for Patients With a Form of Head and Neck Cancer Positive for Human Papilloma Virus 16 and Expressing the Protein PD-L1Phase 2/3 · active · NCT04534205An Open-label Phase II/III Randomized Trial of BNT113 in Combination With Pembrolizumab Versus Pembrolizumab Monotherapy as a First Line Therapy in Patients With Unresectable Recurrent, or Metastatic Head and Neck Squamous Cell Carcinoma (HNSCC) Which is Positive for Human Papilloma Virus 16 (HPV16+) and Expresses PD-L1
- PATHOSPhase 2/3 · active · NCT02215265Resectable HPV-positive oropharyngeal cancer: transoral surgery and neck dissection, then risk-stratified reduction of adjuvant treatment (50 versus 60 Gy in intermediate risk; radiotherapy alone versus chemoradiation in high risk), with swallowing function and survival as endpoints
- A Phase I/IIa Clinical Trial to Investigate BVAC-E6E7 in Subjects With HPV Positive HNSCC.Phase 1/2 · recruiting · NCT06797986A Phase I/IIa Clinical Trial to Investigate the Safety, Immunogenicity and Efficacy of BVAC-E6E7 in Subjects With HPV Type 16 and/or 18 Positive Unresectable Recurrent or Metastatic Head
- A Study to Evaluate Lenti-HPV-07 Immunotherapy Against HPV+ Cervical or Oropharyngeal CancerPhase 1/2 · recruiting · NCT06319963An Open-Label Phase 1/2a Clinical Trial to Evaluate the Safety, Immunogenicity, and Preliminary Efficacy of a Lentiviral Vector-Based Therapeutic Vaccine Against Human Papilloma Virus (Lenti-HPV-07) in Participants With HPV-Associated Oropharyngeal Squamous Cell Cancer or Cervical Cancer
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-positive oropharyngeal cancer: the full pageThroat cancers caused by HPV are usually cured with chemoradiation or robotic surgery, so trials now ask how much treatment can be taken away: swapping cisplatin for cetuximab failed, cutting the radiation dose has worked only after surgery so far, and blood tests for HPV DNA may pick out the patients who can safely have less.
- 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.
- 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.
- Chemoradiation (chemoradiotherapy, CRT): Radiotherapy given at the same time as chemotherapy, which sensitises the cancer to radiation.
Every term links to the glossary.