The first 60 days: HPV-positive oropharyngeal cancer

Staging tests establish exactly what and where the cancer is. Everything else follows from the answers.

• Diagnosis and stagingNCCN Guidelines: Head and Neck Cancers

  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.

  HPV-positive (p16) head and neck cancerPET/CT

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.

1. 1.Prevention

   HPV vaccination of girls and boys before exposure; catch-up vaccination of men is being argued for.

   HPV & HBV vaccinationNonavalent HPV vaccineCatch-up HPV vaccination for men to prevent throat cancer
2. 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.

   Transoral robotic surgery (TORS)IMRT / IGRT (modern external beam)ECOG-ACRIN E3311
3. 3.Locally advanced diseaseNCCN category Category 1, NCCN Guidelines: Head and Neck Cancers

   Cisplatin chemoradiation to 70 Gy; cetuximab only for patients who cannot have cisplatin, since RTOG 1016 and De-ESCALaTE showed it inferior.

   CisplatinChemoradiation (chemoradiotherapy, CRT)IMRT / IGRT (modern external beam)CetuximabRTOG 1016De-ESCALaTE HPV
4. 4.De-escalation

   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.

   NRG-HN002 & NRG-HN005 (HPV+ de-escalation)PATHOSCirculating tumour HPV DNA (ctHPV-DNA)Caution: de-escalating radiation on HPV status alone
5. 5.Recurrent or metastaticNCCN category Category 1, NCCN Guidelines: Head and Neck Cancers

   Pembrolizumab alone or with platinum-fluorouracil (KEYNOTE-048); HPV-positive tumours respond at least as well as HPV-negative ones.

   PembrolizumabKEYNOTE-048Recurrent or metastatic head and neck squamous cell carcinoma
6. 6.Surveillance

   Examination and PET-CT at about three months; circulating tumour HPV DNA is emerging as a blood test for recurrence.

   PET/CTCirculating tumour HPV DNA (ctHPV-DNA)

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.

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
• Response Adaptive Radiotherapy Following Immunotherapy-based Induction for Non-HPV Related HNSCCPhase 2 · recruiting · NCT06345287Response Adaptive Radiotherapy Following Immunotherapy-based Induction for Non-HPV Related Head and Neck Squamous Cell Carcinoma
• 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.

• Free in oncologyFree testing, helplines, rides and lodging, second opinions and trial travel help, with who is eligible.
• Financial helpManufacturer programmes, national schemes and charities by country and product.
• Second opinionExpert centres for this cancer in your country and how referral works.

• 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.