The first 60 days: Head and neck squamous cell carcinoma
Cancers of the mouth and throat, increasingly caused by HPV. Immunotherapy is first line for advanced disease and now used before surgery. Below, week by week, is what OnCo's record of Head and neck squamous cell carcinoma 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.
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: Early HPV-positive oropharynx.
- SurgeonNamed in the standard of care for: Resectable, Early stage (I-II) oral cavity and larynx, Early HPV-positive oropharynx, Locally advanced, resectable (stage III-IVA).
- Medical oncologistNamed in the standard of care for: Resectable, Recurrent/metastatic, Early HPV-positive oropharynx, Locally advanced, resectable (stage III-IVA) and 6 more.
- Clinical oncologist (radiotherapy)Named in the standard of care for: Resectable, Early stage (I-II) oral cavity and larynx, Early HPV-positive oropharynx, Locally advanced, resectable (stage III-IVA) and 4 more.
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 (also prevents oropharyngeal cancer in men), tobacco and alcohol cessation; no validated screening.
Neoadjuvant + adjuvant pembrolizumab with surgery; or chemoradiation.
Single-modality surgery or radiation; sentinel node or elective neck dissection for oral cavity; larynx preservation with radiation for T1-T2 glottic cancer.
TORS with pathology-guided adjuvant therapy or definitive (chemo)radiation; standard 70 Gy dose because de-escalation trials failed.
Neoadjuvant pembrolizumab, surgery, adjuvant pembrolizumab with (chemo)radiation for PD-L1 CPS ≥1 (KEYNOTE-689); otherwise surgery then risk-adapted (chemo)radiation.
Cisplatin (100 mg/m² q3w or weekly) with 70 Gy IMRT; cetuximab-radiation only if cisplatin-ineligible; concurrent immunotherapy is not indicated (JAVELIN Head and Neck 100, KEYNOTE-412) and adding xevinapant to chemoradiation gave no benefit (TrilynX).
Cetuximab sarotalocan photoimmunotherapy; re-irradiation (proton or IMRT) in selected patients elsewhere.
- 8.Recurrent/metastaticESMO-MCBS 2 (cetuximab sarotalocan, Japan, single-arm), NCCN Guidelines: Head and Neck Cancers
Pembrolizumab ± platinum/5-FU; cetuximab-based; photoimmunotherapy (Japan).
Pembrolizumab alone (CPS ≥20, or ≥1) or with platinum/5-FU (any CPS); EXTREME if immunotherapy contraindicated.
Induction gemcitabine-cisplatin then chemoradiation for locoregional disease; toripalimab (or other PD-1) + gemcitabine-cisplatin for recurrent/metastatic; plasma EBV DNA for surveillance.
Nivolumab or pembrolizumab if immunotherapy-naive; otherwise cetuximab, taxane, or methotrexate; clinical trials (bispecifics, ADCs).
- 12.Survivorship
Swallowing and speech therapy, dental care after radiation, thyroid monitoring, lymphoedema management, smoking cessation; second primary surveillance.
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 HPV/p16, PD-L1 CPS, EGFR, HPV / p16 status, PD-L1 CPS), 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 Oral cavity, Oropharynx, HPV-positive, Oropharynx, HPV-negative.
- Is germline (inherited) genetic testing recommended for me or my family?Inherited variants can change treatment and matter for relatives.
Resectable
- For my situation (resectable), which of the standard options do you recommend and why?Guideline options include: Neoadjuvant + adjuvant pembrolizumab with surgery; or chemoradiation.
- 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.
Recurrent/metastatic
- For my situation (recurrent/metastatic), which of the standard options do you recommend and why?Guideline options include: Pembrolizumab ± platinum/5-FU; cetuximab-based; photoimmunotherapy (Japan).
- 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.
Prevention
- For my situation (prevention), which of the standard options do you recommend and why?Guideline options include: HPV vaccination (also prevents oropharyngeal cancer in men), tobacco and alcohol cessation; no validated screening.
Early stage (I-II) oral cavity and larynx
- For my situation (early stage (i-ii) oral cavity and larynx), which of the standard options do you recommend and why?Guideline options include: Single-modality surgery or radiation; sentinel node or elective neck dissection for oral cavity; larynx preservation with radiation for T1-T2 glottic cancer.
Early HPV-positive oropharynx
- For my situation (early hpv-positive oropharynx), which of the standard options do you recommend and why?Guideline options include: TORS with pathology-guided adjuvant therapy or definitive (chemo)radiation; standard 70 Gy dose because de-escalation trials failed.
- How do the results of NRG-HN002 & NRG-HN005 (HPV+ de-escalation) and RTOG 0129 (HPV analysis) apply to someone like me?Trial populations differ from individual patients; ask how closely you match.
Locally advanced, resectable (stage III-IVA)
- For my situation (locally advanced, resectable (stage iii-iva)), which of the standard options do you recommend and why?Guideline options include: Neoadjuvant pembrolizumab, surgery, adjuvant pembrolizumab with (chemo)radiation for PD-L1 CPS ≥1 (KEYNOTE-689); otherwise surgery then risk-adapted (chemo)radiation.
- 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.
Locally advanced, unresectable or organ preservation
- For my situation (locally advanced, unresectable or organ preservation), which of the standard options do you recommend and why?Guideline options include: Cisplatin (100 mg/m² q3w or weekly) with 70 Gy IMRT; cetuximab-radiation only if cisplatin-ineligible; concurrent immunotherapy is not indicated (JAVELIN Head and Neck 100, KEYNOTE-412) and adding xevinapant to chemoradiation gave no benefit (TrilynX).
- How do the results of JAVELIN Head and Neck 100 and TrilynX apply to someone like me?Trial populations differ from individual patients; ask how closely you match.
Recurrent or metastatic, first line
- For my situation (recurrent or metastatic, first line), which of the standard options do you recommend and why?Guideline options include: Pembrolizumab alone (CPS ≥20, or ≥1) or with platinum/5-FU (any CPS); EXTREME if immunotherapy contraindicated.
- 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 and EXTREME apply to someone like me?Trial populations differ from individual patients; ask how closely you match.
Recurrent or metastatic, after platinum
- For my situation (recurrent or metastatic, after platinum), which of the standard options do you recommend and why?Guideline options include: Nivolumab or pembrolizumab if immunotherapy-naive; otherwise cetuximab, taxane, or methotrexate; clinical trials (bispecifics, ADCs).
- Am I a candidate for 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 CheckMate 141 and LiGeR-HN1 apply to someone like me?Trial populations differ from individual patients; ask how closely you match.
Locally recurrent, unresectable (Japan)
- For my situation (locally recurrent, unresectable (japan)), which of the standard options do you recommend and why?Guideline options include: Cetuximab sarotalocan photoimmunotherapy; re-irradiation (proton or IMRT) in selected patients elsewhere.
- Am I a candidate for Cetuximab sarotalocan, and what side effects should I expect?Knowing the expected toxicities helps you plan work, family, and supportive care.
Nasopharyngeal carcinoma
- For my situation (nasopharyngeal carcinoma), which of the standard options do you recommend and why?Guideline options include: Induction gemcitabine-cisplatin then chemoradiation for locoregional disease; toripalimab (or other PD-1) + gemcitabine-cisplatin for recurrent/metastatic; plasma EBV DNA for surveillance.
- Am I a candidate for Toripalimab, and what side effects should I expect?Knowing the expected toxicities helps you plan work, family, and supportive care.
- How do the results of JUPITER-02 apply to someone like me?Trial populations differ from individual patients; ask how closely you match.
Survivorship
- For my situation (survivorship), which of the standard options do you recommend and why?Guideline options include: Swallowing and speech therapy, dental care after radiation, thyroid monitoring, lymphoedema management, smoking cessation; second primary surveillance.
Any stage
- Are there clinical trials I could join, for example of Tilatamig samrotecan, Lifileucel, SHR-A2102, Domvanalimab?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 “Functional toxicity of chemoradiation”. How does that affect my plan?Open problems are where trials and second opinions matter most.
- I read that “Few targets beyond EGFR/PD-1”. 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 Phase 3 Study of AK112 Plus AK117 Versus Pembrolizumab in Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma (R/M HNSCC)Phase 3 · recruiting · NCT06601335A Randomized, Controlled, Multicenter Phase 3 Study of AK112 in Combination With AK117 Versus Pembrolizumab as First Line Treatment for a Programmed Cell Death-ligand 1 (PD-L1) Positive Population With Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma (R/M HNSCC)
- A Phase 3 Study to Evaluate Petosemtamab Compared With Investigator's Choice Monotherapy in Previously Treated Head and Neck Squamous Cell Carcinoma PPhase 3 · active · NCT06496178A Phase 3 Open-label, Randomized Controlled Study to Evaluate the Efficacy and Safety of Petosemtamab Compared With Investigator's Choice Monotherapy Treatment in Previously Treated Patients With Incurable, Metastatic/Recurrent Head and Neck Squamous Cell Carcinoma
- A Study of Amivantamab in Addition to Standard of Care Agents (SOC) Compared With SOC Alone in Participants With Recurrent/Metastatic Head and Neck CancerPhase 3 · recruiting · NCT07276399A Phase 3, Randomized, Open-Label, Multicenter Study of Amivantamab in Addition to Carboplatin and Pembrolizumab, Compared to Standard of Care Platinum and Pembrolizumab and 5-FU, in Participants With Treatment-Naïve Recurrent/Metastatic Head and Neck Squamous Cell Carcinoma
- A Study of ASP-1929 Photoimmunotherapy in Combination With Pembrolizumab in First-line Treatment of Locoregional Recurrent Squamous Cell Carcinoma of Phase 3 · recruiting · NCT06699212A Phase 3 Multicenter, Randomized, Open-label Study of ASP-1929 Photoimmunotherapy in Combination With Pembrolizumab Versus Standard of Care in the First-line Treatment of Patients With Locoregional Recurrence of Squamous Cell Carcinoma of the Head and Neck (HNSCC) With No Distant Metastases
- 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
Much of what helps in the first weeks is free if you know to ask: testing, helplines, rides and lodging, second opinions, trial travel.
- Head and neck squamous cell carcinoma: the full pageCancers of the mouth and throat, increasingly caused by HPV. Immunotherapy is first line for advanced disease and now used before surgery.
- 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.
- TNM staging: TNM staging is the universal system describing tumour size (T), lymph node spread (N), and distant metastasis (M).
- Dysphagia (difficulty swallowing): Trouble swallowing, either because a tumour narrows the food pipe or throat, or because radiotherapy and surgery to the head, neck or chest have damaged the muscles and nerves that coordinate swallowing.
- Head and neck subsites (oral cavity, oropharynx, larynx): Head and neck cancer is really several cancers named by exact location: mouth (oral cavity), back of the throat (oropharynx, where HPV cancers arise), voice box (larynx), lower throat (hypopharynx) and behind the nose (nasopharynx).
- LGR5: A marker of stem cells in the gut and of stem-like cells in tumours, used to aim drugs at the cells that regrow a cancer.
- Feeding tube (gastrostomy, PEG, jejunostomy): A tube placed into the stomach (gastrostomy, PEG) or small bowel (jejunostomy) so a patient who cannot swallow enough can still be fed through the gut.
- Organ preservation (watch-and-wait, bladder-sparing, larynx preservation): Curing a cancer with drugs and radiotherapy so that the organ (rectum, bladder, larynx, limb) does not have to be removed, keeping surgery in reserve for the minority whose cancer regrows.
- Dose-dense and metronomic chemotherapy: Two opposite ways of rescheduling the same drugs: dose-dense gives standard doses more often (every two weeks instead of three, supported by growth factors) to deny the tumour recovery time; metronomic gives small doses continuously to attack tumour blood vessels with little toxicity.
- Perineural invasion (PNI): Cancer cells growing along the sheath of a nerve.
- Radiation dermatitis (skin reaction): Redness, dryness, itching and sometimes peeling of the skin in the treated area, building up over the course and settling a few weeks after it ends.
- Nutrition impact symptoms: The side-effects of cancer and its treatment that stop people eating: nausea, mouth soreness, taste changes, difficulty swallowing, early fullness, constipation, pain and low mood.
Every term links to the glossary.