OnCo
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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.

Head and neck squamous cell carcinoma arises from the lining of the mouth, throat (oropharynx, hypopharynx), voice box, and nose, and includes the distinct Epstein-Barr-virus-driven nasopharyngeal carcinoma. Two epidemics coexist: tobacco- and alcohol-related cancers, declining in rich countries but common globally, and HPV-driven oropharyngeal cancer, rising among younger non-smokers and now the most common HPV cancer in the US. HPV-positive disease is far more curable (3-year survival >80%) and has its own staging system.

Curative treatment is surgery (increasingly transoral robotic surgery) and/or cisplatin-based chemoradiation with IMRT; both leave lasting effects on speech, swallowing, and salivation, which is why de-escalation for HPV-positive disease has been pursued so hard, and why its repeated failure (RTOG 1016, De-ESCALaTE, NRG-HN005) matters. Immunotherapy transformed recurrent and metastatic disease: nivolumab (CheckMate 141) and then pembrolizumab first line (KEYNOTE-048) replaced the cetuximab-chemotherapy EXTREME regimen, and in June 2025 KEYNOTE-689 delivered the first perioperative approval, doubling event-free survival by giving pembrolizumab before and after surgery. Immunotherapy given concurrently with chemoradiation, by contrast, has failed repeatedly. Nasopharyngeal carcinoma gained its first US approval with toripalimab plus chemotherapy in 2023.

What is coming: EGFR-directed bispecifics with pembrolizumab (petosemtamab, ficerafusp alfa) posting response rates two to three times those of pembrolizumab alone in early trials, now in phase 3; photoimmunotherapy (approved in Japan) in global phase 3; ctHPV-DNA to guide response-adapted de-escalation; and B7-H3 and EGFR×HER3 ADCs. Open problems include the lack of targets beyond EGFR and PD-1, the functional toxicity of curative treatment, and the poor prognosis of HPV-negative disease.

State of the art today

  • Perioperative IO.
  • HPV vaccination reducing future incidence.
  • HPV-positive oropharyngeal cancer is recognised as a distinct, highly curable disease, but the standard dose of chemoradiation still stands because every de-escalation trial has fallen short.
  • Nasopharyngeal carcinoma has immunotherapy-chemotherapy as first line in the US, EU, and China.
  • Transoral robotic surgery gives many patients a surgical option without splitting the jaw.
  • EGFR-directed bispecifics plus PD-1 blockade are showing response rates not seen before in this disease and are in phase 3.
Show survival figures (2)

Averages across everyone diagnosed, often years ago. Your stage, subtype, age, fitness and the treatment you receive matter more than the average, and the numbers are improving quickly.

  • Perioperative pembrolizumab (KEYNOTE-689) is the first curative-intent advance since cetuximab-radiation in 2006, with median event-free survival roughly doubled.
  • Pembrolizumab-based first-line therapy for recurrent or metastatic disease produces a durable survival tail that chemotherapy never did.
Who it affects

~900,000 cases per year; HPV-driven oropharyngeal cancer rising, tobacco-related declining.

Where the cases are

Cases by country · GLOBOCAN 2022
All countries →

Site: Head and neck (lip/oral, salivary, oro-, naso-, hypopharynx, larynx). World: 947,211 new cases, 482,428 deaths.

#CountryNew casesDeaths
1India247,924137,925
2China145,60380,437
3United States of America63,44013,925
4Bangladesh36,80820,850
5Indonesia33,60321,155
6Brazil29,66915,402
7Japan26,3199,561
8Russian Federation26,14914,555
9Pakistan24,65215,568
10France (metropolitan)17,8375,333

Sum of six GLOBOCAN sites. Counts and age-standardised rates add; cumulative risk is left blank.

Standard of care

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Resectable

Neoadjuvant + adjuvant pembrolizumab with surgery; or chemoradiation.

NCCN Guidelines: Head and Neck Cancers
PembrolizumabIMRT / IGRT (modern external beam)Robotic & minimally invasive surgery
Recurrent/metastatic

Pembrolizumab ± platinum/5-FU; cetuximab-based; photoimmunotherapy (Japan).

ESMO-MCBS · 2 (cetuximab sarotalocan, Japan, single-arm)
PembrolizumabPhotoimmunotherapy & photodynamic therapy
Prevention

HPV vaccination (also prevents oropharyngeal cancer in men), tobacco and alcohol cessation; no validated screening.

NCCN · Prevention guideline
HPV & HBV vaccination
Early stage (I-II) oral cavity and larynx

Single-modality surgery or radiation; sentinel node or elective neck dissection for oral cavity; larynx preservation with radiation for T1-T2 glottic cancer.

NCCN · 2A
IMRT / IGRT (modern external beam)Sentinel lymph node biopsy
Early HPV-positive oropharynx

TORS with pathology-guided adjuvant therapy or definitive (chemo)radiation; standard 70 Gy dose because de-escalation trials failed.

NCCN · 2A
Transoral robotic surgery (TORS)NRG-HN002 & NRG-HN005 (HPV+ de-escalation)Caution: de-escalating radiation on HPV status aloneRTOG 0129 (HPV analysis)
Locally advanced, resectable (stage III-IVA)

Neoadjuvant pembrolizumab, surgery, adjuvant pembrolizumab with (chemo)radiation for PD-L1 CPS ≥1 (KEYNOTE-689); otherwise surgery then risk-adapted (chemo)radiation.

NCCN · 1 (CPS ≥1)ESMO-MCBS · A
KEYNOTE-689PembrolizumabImmunotherapy before surgery rather than with chemoradiation (HNSCC)
Locally advanced, unresectable or organ preservation

Cisplatin (100 mg/m² q3w or weekly) with 70 Gy IMRT; cetuximab-radiation only if cisplatin-ineligible; concurrent immunotherapy is not indicated (JAVELIN, KEYNOTE-412).

NCCN · 1
IMRT / IGRT (modern external beam)JAVELIN Head and Neck 100TrilynX
Recurrent or metastatic, first line

Pembrolizumab alone (CPS ≥20, or ≥1) or with platinum/5-FU (any CPS); EXTREME if immunotherapy contraindicated.

NCCN · 1ESMO-MCBS · 4
KEYNOTE-048PembrolizumabEXTREME
Recurrent or metastatic, after platinum

Nivolumab or pembrolizumab if immunotherapy-naive; otherwise cetuximab, taxane, or methotrexate; clinical trials (bispecifics, ADCs).

NCCN · 1 (IO-naive)
CheckMate 141NivolumabLiGeR-HN1FORTIFI-HN01
Locally recurrent, unresectable (Japan)

Cetuximab sarotalocan photoimmunotherapy; re-irradiation (proton or IMRT) in selected patients elsewhere.

Cetuximab sarotalocanPhotoimmunotherapy & photodynamic therapyProton therapyBoron neutron capture therapy
Nasopharyngeal carcinoma

Induction gemcitabine-cisplatin then chemoradiation for locoregional disease; toripalimab (or other PD-1) + gemcitabine-cisplatin for recurrent/metastatic; plasma EBV DNA for surveillance.

NCCN · 1
JUPITER-02ToripalimabIMRT / IGRT (modern external beam)
Survivorship

Swallowing and speech therapy, dental care after radiation, thyroid monitoring, lymphoedema management, smoking cessation; second primary surveillance.

Supportive Care & Survivorship

Subtypes & biomarkers

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Subtypes
Biomarkers clinicians test
  • HPV/p16
  • PD-L1 CPS
  • EGFR
  • HPV / p16 status (staging and prognosis)
  • PD-L1 CPS (first-line pembrolizumab eligibility and KEYNOTE-689)
  • EGFR (near-universal; cetuximab, bispecifics)
  • EBV DNA (nasopharyngeal carcinoma surveillance)
  • ctHPV-DNA (response and recurrence)
  • TP53, CDKN2A, PIK3CA, NOTCH1 (HPV-negative genomics)
  • Smoking history (modifies HPV-positive prognosis)

Target prevalence in this cancer

Target / alterationPrevalenceSource
EGFR
80-90%
Wikipedia
PD-L1
KEYNOTE-048
80-85%
Wikipedia
PIK3CA / PI3K-alpha
HPV+ enriched
15-20%
cBioPortal (TCGA)

How common each drug target or alteration is in this cancer. Population-level and approximate; see the target page for detail. Full matrix.

History

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  1. 1987Cisplatin-5-FU induction and larynx preservation trials begin

    VA Larynx study establishes organ preservation with chemoradiation.

  2. 2000Concurrent cisplatin chemoradiation becomes standard for locally advanced disease

    Meta-analysis (MACH-NC) confirms ~6.5% absolute survival gain.

    IMRT / IGRT (modern external beam)Platinum agents
  3. 2006Cetuximab + RT
  4. 2006Cetuximab + radiation improves survival (Bonner)

    First targeted agent in HNSCC.

    EGFR
  5. 2008EXTREME defines first-line therapy for recurrent/metastatic disease
    EXTREME
  6. 2009Transoral robotic surgery FDA-cleared
    Transoral robotic surgery (TORS)
  7. 2010RTOG 0129: HPV status is the dominant prognostic factor
    RTOG 0129 (HPV analysis)HPV-positive (p16) head and neck cancer
  8. 2016PD-1 approved second line
  9. 2016Nivolumab (CheckMate 141) and pembrolizumab approved after platinum
    CheckMate 141NivolumabPembrolizumab
  10. 2018AJCC 8th edition gives HPV-positive oropharynx cancer its own staging
    HPV-positive (p16) head and neck cancerTNM staging
  11. 2019KEYNOTE-048: IO first line
  12. 2019KEYNOTE-048: pembrolizumab first line; RTOG 1016 and De-ESCALaTE show cetuximab cannot replace cisplatin
    KEYNOTE-048Caution: de-escalating radiation on HPV status alone
  13. 2020Cetuximab sarotalocan photoimmunotherapy approved in Japan; JAVELIN H&N 100 negative
    Cetuximab sarotalocanJAVELIN Head and Neck 100
  14. 2021JUPITER-02: PD-1 plus chemotherapy in nasopharyngeal carcinoma; BNCT approved in Japan
    JUPITER-02Boron neutron capture therapy
  15. 2023Toripalimab first US approval for nasopharyngeal carcinoma
    Toripalimab
  16. 2024TrilynX (xevinapant) stopped for futility; petosemtamab Breakthrough designation
    TrilynXPetosemtamab
  17. 2025KEYNOTE-689: neoadjuvant IO
  18. 2025KEYNOTE-689 perioperative pembrolizumab approved; NRG-HN005 de-escalation fails; petosemtamab and ficerafusp alfa phase 3 trials
    KEYNOTE-689NRG-HN002 & NRG-HN005 (HPV+ de-escalation)LiGeR-HN1FORTIFI-HN01

Pipeline

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Phase 2Bispecific ADC
Tilatamig samrotecan
ApprovedTIL cell therapy
Lifileucel · Amtagvi
Phase 3Bispecific antibody (EGFR × LGR5)
Petosemtamab
Phase 3Bifunctional antibody (EGFR × TGF-β trap)
Ficerafusp alfa
Under reviewPhotoimmunotherapy conjugate (anti-EGFR antibody–IR700 dye)
Cetuximab sarotalocan · Akalux
LiGeR-HN1FORTIFI-HN01Circulating tumour HPV DNA (ctHPV-DNA)ctHPV-DNA-adapted de-escalation of chemoradiationPhotoimmunotherapy as an in situ vaccine with PD-1 blockadeEGFR-directed bispecific + PD-1 blockadeBoron neutron capture therapyProton therapyB7-H3

Open problems

  • Functional toxicity of chemoradiation.
  • Few targets beyond EGFR/PD-1.
  • HPV-negative, tobacco-related disease has 5-year survival around 50% and has seen little improvement in curative outcomes beyond KEYNOTE-689.
  • De-escalation for HPV-positive disease has failed in every randomised trial; the field still lacks a validated way to identify who can receive less.
  • Only two drug targets (EGFR and PD-1) have approved agents; PIK3CA, NOTCH, and CDKN2A alterations remain undrugged.
  • Immunotherapy concurrent with chemoradiation has failed three times; the mechanism is not fully understood.
  • Curative treatment causes permanent swallowing, speech, dental, and thyroid damage; survivorship care is under-resourced.
  • Nasopharyngeal carcinoma outside East Asia is rare and under-studied; EBV-directed cell therapies remain experimental.
  • Second primary cancers and field cancerisation in smokers are not addressed by any approved chemoprevention.
  • Global burden falls on South Asia (oral cavity cancer from smokeless tobacco and areca nut), where access to IMRT and immunotherapy is limited.

Trials

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Recruiting now (live from ClinicalTrials.gov)

Recruiting trials near you · live from ClinicalTrials.gov
Head and neck squamous cell carcinoma
condition: head and neck squamous cell carcinoma
Open on ClinicalTrials.gov →

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Landmark trials in OnCo

CheckMate 141EXTREMEFORTIFI-HN01JAVELIN Head and Neck 100JUPITER-02KEN SHE (single-dose HPV vaccine)KEYNOTE-048KEYNOTE-689LiGeR-HN1NRG-HN002 & NRG-HN005 (HPV+ de-escalation)RTOG 0129 (HPV analysis)TrilynX

Expert centres

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Where the expertise is

Centres linked to this cancer in OnCo

Seeking a second opinion: ask your oncologist for a referral to a high-volume centre; most accept records and pathology by mail or telehealth. In the US, use the NCI's Find a Cancer Center tool or the nonprofit Cancer Commons, which navigates options for advanced cancers at no cost.

Questions to ask

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Bring to your appointment

Questions to ask your oncologist about Head and neck squamous cell carcinoma

Generated from this cancer's standard of care, biomarkers, and pipeline · 34 questions

Newly diagnosed

  1. What is my exact diagnosis, stage, and grade, and which tests established them?
    Why: Everything else follows from an accurate stage and subtype.
  2. 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?
    Why: These results decide eligibility for targeted therapy, immunotherapy, and trials.
  3. Which subtype is my cancer, and does that change the recommended treatment?
    Why: Recognised subtypes for this cancer include Oral cavity, Oropharynx, HPV-positive, Oropharynx, HPV-negative.
  4. Is germline (inherited) genetic testing recommended for me or my family?
    Why: Inherited variants can change treatment and matter for relatives.

Resectable

  1. For my situation (resectable), which of the standard options do you recommend and why?
    Why: Guideline options include: Neoadjuvant + adjuvant pembrolizumab with surgery; or chemoradiation.
  2. Am I a candidate for Pembrolizumab, and what side effects should I expect?
    Why: Knowing the expected toxicities helps you plan work, family, and supportive care.

Recurrent/metastatic

  1. For my situation (recurrent/metastatic), which of the standard options do you recommend and why?
    Why: Guideline options include: Pembrolizumab ± platinum/5-FU; cetuximab-based; photoimmunotherapy (Japan).
  2. Am I a candidate for Pembrolizumab, and what side effects should I expect?
    Why: Knowing the expected toxicities helps you plan work, family, and supportive care.

Prevention

  1. For my situation (prevention), which of the standard options do you recommend and why?
    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

  1. For my situation (early stage (i-ii) oral cavity and larynx), which of the standard options do you recommend and why?
    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

  1. For my situation (early hpv-positive oropharynx), which of the standard options do you recommend and why?
    Why: Guideline options include: TORS with pathology-guided adjuvant therapy or definitive (chemo)radiation; standard 70 Gy dose because de-escalation trials failed.
  2. How do the results of NRG-HN002 & NRG-HN005 (HPV+ de-escalation) and RTOG 0129 (HPV analysis) apply to someone like me?
    Why: Trial populations differ from individual patients; ask how closely you match.

Locally advanced, resectable (stage III-IVA)

  1. For my situation (locally advanced, resectable (stage iii-iva)), which of the standard options do you recommend and why?
    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.
  2. Am I a candidate for Pembrolizumab, and what side effects should I expect?
    Why: Knowing the expected toxicities helps you plan work, family, and supportive care.
  3. How do the results of KEYNOTE-689 apply to someone like me?
    Why: Trial populations differ from individual patients; ask how closely you match.

Locally advanced, unresectable or organ preservation

  1. For my situation (locally advanced, unresectable or organ preservation), which of the standard options do you recommend and why?
    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, KEYNOTE-412).
  2. How do the results of JAVELIN Head and Neck 100 and TrilynX apply to someone like me?
    Why: Trial populations differ from individual patients; ask how closely you match.

Recurrent or metastatic, first line

  1. For my situation (recurrent or metastatic, first line), which of the standard options do you recommend and why?
    Why: Guideline options include: Pembrolizumab alone (CPS ≥20, or ≥1) or with platinum/5-FU (any CPS); EXTREME if immunotherapy contraindicated.
  2. Am I a candidate for Pembrolizumab, and what side effects should I expect?
    Why: Knowing the expected toxicities helps you plan work, family, and supportive care.
  3. How do the results of KEYNOTE-048 and EXTREME apply to someone like me?
    Why: Trial populations differ from individual patients; ask how closely you match.

Recurrent or metastatic, after platinum

  1. For my situation (recurrent or metastatic, after platinum), which of the standard options do you recommend and why?
    Why: Guideline options include: Nivolumab or pembrolizumab if immunotherapy-naive; otherwise cetuximab, taxane, or methotrexate; clinical trials (bispecifics, ADCs).
  2. Am I a candidate for Nivolumab, and what side effects should I expect?
    Why: Knowing the expected toxicities helps you plan work, family, and supportive care.
  3. How do the results of CheckMate 141 and LiGeR-HN1 apply to someone like me?
    Why: Trial populations differ from individual patients; ask how closely you match.

Locally recurrent, unresectable (Japan)

  1. For my situation (locally recurrent, unresectable (japan)), which of the standard options do you recommend and why?
    Why: Guideline options include: Cetuximab sarotalocan photoimmunotherapy; re-irradiation (proton or IMRT) in selected patients elsewhere.
  2. Am I a candidate for Cetuximab sarotalocan, and what side effects should I expect?
    Why: Knowing the expected toxicities helps you plan work, family, and supportive care.

Nasopharyngeal carcinoma

  1. For my situation (nasopharyngeal carcinoma), which of the standard options do you recommend and why?
    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.
  2. Am I a candidate for Toripalimab, and what side effects should I expect?
    Why: Knowing the expected toxicities helps you plan work, family, and supportive care.
  3. How do the results of JUPITER-02 apply to someone like me?
    Why: Trial populations differ from individual patients; ask how closely you match.

Survivorship

  1. For my situation (survivorship), which of the standard options do you recommend and why?
    Why: Guideline options include: Swallowing and speech therapy, dental care after radiation, thyroid monitoring, lymphoedema management, smoking cessation; second primary surveillance.

Any stage

  1. Are there clinical trials I could join, for example of Tilatamig samrotecan, Lifileucel, Petosemtamab, LiGeR-HN1?
    Why: Trials are how the next standard of care is set; asking early keeps options open.
  2. Would a second opinion at a high-volume centre change anything, and can you help arrange it?
    Why: Rare or high-stakes decisions benefit from a centre that treats many similar patients.
  3. What supportive care (symptom control, nutrition, exercise, mental health, financial help) is available from the start?
    Why: Supportive care improves quality of life and helps patients complete treatment.
  4. I read that “Functional toxicity of chemoradiation”. How does that affect my plan?
    Why: Open problems are where trials and second opinions matter most.
  5. I read that “Few targets beyond EGFR/PD-1”. How does that affect my plan?
    Why: Open problems are where trials and second opinions matter most.

Print this page for your appointment (your browser's print command). These prompts are for discussion; your clinical team knows your case.

Everything relevant

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Direct links plus the targets, companies, and technologies of this cancer's products.

fronts

1
Supportive Care & Survivorship

technologies

28
Alcohol reduction, pricing and cancer warning labelsBispecific ADCBispecific antibodiesBoron neutron capture therapyCirculating tumour HPV DNA (ctHPV-DNA)Cytotoxic chemotherapyDietary supplements during cancer treatment: interactions and harmsElectrochemotherapyEnteral and parenteral nutrition supportHPV & HBV vaccinationImmune checkpoint inhibitorsImmunonutrition before cancer surgeryIMRT / IGRT (modern external beam)Monoclonal antibodiesNutrition support and cachexia managementOncology nutrition assessment and medical nutrition therapyPhotoimmunotherapy & photodynamic therapyPlatinum agentsProton therapyRadiodynamic therapy and radiosensitising nanoparticlesResistance training and protein for cachexia and sarcopeniaRobotic & minimally invasive surgerySentinel lymph node biopsySmoking cessation in cancer patientsSPECT & bone scanSTING & innate immune agonistsTIL therapyTransoral robotic surgery (TORS)

targets

6
B7-H3EGFRMETPD-1PD-L1PIK3CA / PI3K-alpha

drugs

16
WithdrawnSmall molecule (STING agonist, intratumoural)
ADU-S100 (MIW815)
ApprovedMonoclonal antibody (anti-EGFR)
Cetuximab · Erbitux
Under reviewPhotoimmunotherapy conjugate (anti-EGFR antibody–IR700 dye)
Cetuximab sarotalocan · Akalux
ApprovedCytotoxic chemotherapy (platinum)
Cisplatin · Platinol (generic)
ApprovedCytotoxic chemotherapy (taxane)
Docetaxel · Taxotere (generic)
Phase 3Bifunctional antibody (EGFR × TGF-β trap)
Ficerafusp alfa
Not mapped hereFluoropyrimidine antimetabolite
Fluorouracil (5-FU) · Adrucil / Efudex
ApprovedTIL cell therapy
Lifileucel · Amtagvi
Not mapped hereAntifolate (DHFR inhibitor)
Methotrexate · Trexall / Otrexup / Xatmep
ApprovedMonoclonal antibody (anti-PD-1)
Nivolumab · Opdivo / Opdivo Qvantig (SC)
ApprovedProphylactic vaccine (virus-like particles)
Nonavalent HPV vaccine · Gardasil 9
ApprovedMonoclonal antibody (anti-PD-1)
Pembrolizumab · Keytruda / Keytruda Qlex (SC)
Phase 3Bispecific antibody (EGFR × LGR5)
Petosemtamab
Not mapped hereRadiopharmaceutical lymphatic mapping agent
Technetium-99m tilmanocept · Lymphoseek
Phase 2Bispecific ADC
Tilatamig samrotecan
ApprovedMonoclonal antibody (anti-PD-1)
Toripalimab · Loqtorzi

companies

12
AstraZenecaBristol Myers SquibbDebiopharmEli Lilly (incl. Loxo)GenmabIntuitive SurgicalIovance BiotherapeuticsMerck & Co. (MSD)Mersana TherapeuticsMerusNovartisSanofi

institutions

59
A.C. Camargo Cancer CenterAarhus University HospitalAdvanced Centre for Treatment, Research and Education in CancerAll India Institute of Medical Sciences, New DelhiApollo Hospitals (Apollo Cancer Centres)Cancer Institute (WIA), AdyarCentre Antoine LacassagneCentre Oscar LambretChang Gung Memorial HospitalChao Family Comprehensive Cancer Center, UC IrvineChris O'Brien LifehouseChristian Medical College, VelloreDana-Farber Brigham Cancer CenterDharmais National Cancer CenterGhent University Hospital / Cancer Research Institute GhentGroote Schuur Hospital / University of Cape TownGunma University Heavy Ion Medical CenterHacettepe University Cancer InstituteHealthCare Global EnterprisesHo Chi Minh City Oncology HospitalHokkaido University HospitalInstitut National d'Oncologie, RabatInstitut PasteurInstitut Salah AzaïezInstitute of Oncology LjubljanaIstanbul University Institute of OncologyIUCT Oncopole – Institut Universitaire du Cancer de ToulouseKidwai Memorial Institute of OncologyKoo Foundation Sun Yat-Sen Cancer CenterMUSC Hollings Cancer CenterNational Cancer Center Hospital EastNational Cancer Centre SingaporeNational Institute of Oncology, HungaryNCT/UCC Dresden – University Hospital Carl Gustav CarusNRG OncologyO'Neal Comprehensive Cancer Center at UABOcean Road Cancer InstitutePhilippine General HospitalPrince of Wales Hospital / Chinese University of Hong KongQIMR Berghofer Medical Research InstituteQST Hospital (National Institutes for Quantum Science and Technology)Queen Mary Hospital / University of Hong KongRajiv Gandhi Cancer Institute and Research CentreShandong Cancer Hospital and InstituteShizuoka Cancer CenterSiriraj Hospital, Mahidol UniversitySun Yat-sen University Cancer CenterTata Medical Center, KolkataTata Memorial CentreTianjin Medical University Cancer Institute and HospitalTROG Cancer ResearchUC San Diego Moores Cancer CenterUMC Utrecht Cancer CenterUniversity of Chicago Medicine Comprehensive Cancer CenterUniversity of Malaya Medical CentreUPMC Hillman Cancer CenterVelindre Cancer CentreVietnam National Cancer Hospital (K Hospital)Zhejiang Cancer Hospital

pathways

5
Cancer neuroscience (nerve–tumour signalling)Field cancerisationInvasion: proteases, adhesion & the invasive frontNotch signallingOncogenic viruses

terms

20
Alcohol-attributable cancerChemoradiation (chemoradiotherapy, CRT)Combined positive score (CPS)Dose-dense and metronomic chemotherapyDysphagia (difficulty swallowing)Epstein-Barr virus (EBV) in cancerFeeding tube (gastrostomy, PEG, jejunostomy)Head and neck subsites (oral cavity, oropharynx, larynx)HPV status (HPV-positive / HPV-negative)HPV-positive (p16) head and neck cancerInduction therapyLGR5Neoadjuvant / adjuvant / perioperativeNutrition impact symptomsOrgan preservation (watch-and-wait, bladder-sparing, larynx preservation)Perineural invasion (PNI)Re-irradiationSquamous cell carcinomaSquamous cell carcinoma (SCC)TNM staging

trials

12
CheckMate 141EXTREMEFORTIFI-HN01JAVELIN Head and Neck 100JUPITER-02KEN SHE (single-dose HPV vaccine)KEYNOTE-048KEYNOTE-689LiGeR-HN1NRG-HN002 & NRG-HN005 (HPV+ de-escalation)RTOG 0129 (HPV analysis)TrilynX

pairings

3
Caution: de-escalating radiation on HPV status aloneEGFR-directed bispecific + PD-1 blockadeImmunotherapy before surgery rather than with chemoradiation (HNSCC)

roadmaps

1
Immunotherapy roadmap: Coley's toxins → checkpoint inhibitors → engineered immunity

ideas

35
A coordinated FLASH radiotherapy evidence programme with shared dose-rate standardsA dietitian in every gastrointestinal and head and neck tumour boardA funded programme of organ-preservation trials to avoid radical surgeryA platform trial of very-low-cost metronomic chemotherapy in LMIC common cancersA pragmatic trial network for intraoperative margin tools, paid on margin reductionA short pre-surgery drug window as the default early test of new agentsA standing platform for testing new drugs with radiotherapyAn Epstein-Barr virus vaccine to prevent nasopharyngeal cancer and lymphomasBlended finance and a low-cost linac to close the global radiotherapy gapBlood EBV DNA screening for nasopharyngeal cancer across southern China and Southeast AsiaBurden-matched funding for trials led in low- and middle-income countriesCatch-up HPV vaccination for men to prevent throat cancerClear the suppressive neutrophils out of pancreatic tumours firstCommunity health workers with smartphone AI screen for mouth cancer in South AsiaCommunity-tailored HPV vaccine confidence campaigns with school-based deliveryConfirm ultra-low-dose immunotherapy so it can be afforded where most patients livectHPV-DNA-adapted de-escalation of chemoradiationCut the nerve supply to tumours with old drugsEliminate infection-caused cancers: HPV, hepatitis B and C, H. pylori and EBVEvaluate alcohol minimum unit pricing against cancer incidenceIntercept cancer at the field stageKeep dormant cells asleep instead of trying to kill themMake a two-minute mouth cancer check part of every dental visitPhotobiomodulation and a taste and swallowing programme for mouth and throat toxicityPhotoimmunotherapy as an in situ vaccine with PD-1 blockadePre-surgery platform trials that test combinations on pathological response in monthsProtect hearing from cisplatin in adults as we now do in childrenRadiotherapy for everyone who needs it by 2040Real-time margin assessment and image-guided surgery as the global standardStanding reflex biomarker panels per tumour type, run without an oncologist's orderSwitch every country to single-dose HPV vaccination and add catch-up to age 26Treat the draining lymph node before removing itTurn one tumour into a vaccine to treat all the othersTwo-week pre-operative windows to compare combination biology head to headValidate low-cost metronomic oral regimens in phase 3 and carry them into guidelines

people

24
Beatriz CasteloCharu AggarwalChristine H. ChungChristophe Le TourneauDeborah Watkins BrunerDenise A. GallowayDouglas R. LowyEverett E. VokesHarald zur HausenHye Ryun KimJohn V. HeymachJun MaKevin HarringtonKumar PrabhashLi ZhangLillian L. SiuMarco GuzzoMu-Sheng ZengMyung-Ju AhnPankaj ChaturvediUlrich KeilholzVanita NoronhaVijay PatilWenfeng Fang

bottlenecks

5
Cachexia, toxicity and the limits of the patientFragmented care and guideline gapsMost of the world has almost no cancer careNo one can predict who responds to immunotherapyPrevention we already have is not deployed

key papers

4
Alcohol caused an estimated 741,000 cancers worldwide in 2020Fifty years of the British Doctors Study: smokers lose ten years of life, quitting gives most of it backKEYNOTE-048: pembrolizumab, alone or with chemotherapy, as first treatment for recurrent or metastatic head and neck cancerSwedish registry study: HPV vaccination almost eliminates cervical cancer when given before 17

Key papers

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observationalLancet Oncology 2021
Alcohol caused an estimated 741,000 cancers worldwide in 2020

There is no safe level of alcohol for cancer risk, and the risk is highest for cancers of the mouth, throat, oesophagus, liver, bowel and breast. Public awareness is low; most people do not know alcohol causes breast cancer. Warning labels and minimum pricing are the policy levers being debated.

observationalNew England Journal of Medicine 2020changed practice
Swedish registry study: HPV vaccination almost eliminates cervical cancer when given before 17

Vaccinating girls before they are exposed to HPV prevents most cervical cancers. Catch-up vaccination in young adults still helps, but less. Combined with HPV screening, elimination of cervical cancer as a public health problem is a realistic goal.

rctThe Lancet 2019changed practice
KEYNOTE-048: pembrolizumab, alone or with chemotherapy, as first treatment for recurrent or metastatic head and neck cancer

Patients with head and neck squamous cell cancer that has recurred or spread should be treated first with pembrolizumab: alone if their tumour is strongly PD-L1 positive and they can wait for a slower response, or with chemotherapy if the tumour is bulky or PD-L1 low. Cetuximab-based chemotherapy is no longer the default. Long-term follow-up shows a small but real group of patients alive at four to five years, which was almost unheard of before.

observationalBMJ 2004changed practice
Fifty years of the British Doctors Study: smokers lose ten years of life, quitting gives most of it back

Smoking is the single largest preventable cause of cancer death, and quitting at any age helps, with the greatest gain from quitting young. Cessation support belongs in every cancer service, including lung screening programmes.

Latest papers

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Query for this cancer: (TITLE:"Head and neck squamous cell carcinoma" OR ABSTRACT:"Head and neck squamous cell carcinoma") AND (treatment OR therapy OR trial OR survival OR diagnosis). Results are unfiltered search hits about Head and neck squamous cell carcinoma, not a curated reading list.

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fronts

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Supportive Care & Survivorship

technologies

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Alcohol reduction, pricing and cancer warning labelsBoron neutron capture therapyCirculating tumour HPV DNA (ctHPV-DNA)Dietary supplements during cancer treatment: interactions and harmsElectrochemotherapyEnteral and parenteral nutrition supportHPV & HBV vaccinationImmune checkpoint inhibitorsImmunonutrition before cancer surgeryIMRT / IGRT (modern external beam)Nutrition support and cachexia managementOncology nutrition assessment and medical nutrition therapyPhotoimmunotherapy & photodynamic therapyPlatinum agentsProton therapyRadiodynamic therapy and radiosensitising nanoparticlesResistance training and protein for cachexia and sarcopeniaRobotic & minimally invasive surgerySentinel lymph node biopsySmoking cessation in cancer patientsTransoral robotic surgery (TORS)

targets

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B7-H3EGFRPD-1PD-L1PIK3CA / PI3K-alpha

drugs

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WithdrawnSmall molecule (STING agonist, intratumoural)
ADU-S100 (MIW815)
ApprovedMonoclonal antibody (anti-EGFR)
Cetuximab · Erbitux
Under reviewPhotoimmunotherapy conjugate (anti-EGFR antibody–IR700 dye)
Cetuximab sarotalocan · Akalux
ApprovedCytotoxic chemotherapy (platinum)
Cisplatin · Platinol (generic)
ApprovedCytotoxic chemotherapy (taxane)
Docetaxel · Taxotere (generic)
Phase 3Bifunctional antibody (EGFR × TGF-β trap)
Ficerafusp alfa
Not mapped hereFluoropyrimidine antimetabolite
Fluorouracil (5-FU) · Adrucil / Efudex
ApprovedTIL cell therapy
Lifileucel · Amtagvi
Not mapped hereAntifolate (DHFR inhibitor)
Methotrexate · Trexall / Otrexup / Xatmep
ApprovedMonoclonal antibody (anti-PD-1)
Nivolumab · Opdivo / Opdivo Qvantig (SC)
ApprovedProphylactic vaccine (virus-like particles)
Nonavalent HPV vaccine · Gardasil 9
ApprovedMonoclonal antibody (anti-PD-1)
Pembrolizumab · Keytruda / Keytruda Qlex (SC)
Phase 3Bispecific antibody (EGFR × LGR5)
Petosemtamab
Not mapped hereRadiopharmaceutical lymphatic mapping agent
Technetium-99m tilmanocept · Lymphoseek
Phase 2Bispecific ADC
Tilatamig samrotecan
ApprovedMonoclonal antibody (anti-PD-1)
Toripalimab · Loqtorzi

companies

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Bristol Myers SquibbDebiopharmGenmabIntuitive SurgicalMerck & Co. (MSD)Mersana TherapeuticsMerus

institutions

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A.C. Camargo Cancer CenterAarhus University HospitalAdvanced Centre for Treatment, Research and Education in CancerAll India Institute of Medical Sciences, New DelhiApollo Hospitals (Apollo Cancer Centres)Cancer Institute (WIA), AdyarCentre Antoine LacassagneCentre Oscar LambretChang Gung Memorial HospitalChao Family Comprehensive Cancer Center, UC IrvineChris O'Brien LifehouseChristian Medical College, VelloreDana-Farber Brigham Cancer CenterDharmais National Cancer CenterGhent University Hospital / Cancer Research Institute GhentGroote Schuur Hospital / University of Cape TownGunma University Heavy Ion Medical CenterHacettepe University Cancer InstituteHealthCare Global EnterprisesHo Chi Minh City Oncology HospitalHokkaido University HospitalInstitut National d'Oncologie, RabatInstitut PasteurInstitut Salah AzaïezInstitute of Oncology LjubljanaIstanbul University Institute of OncologyIUCT Oncopole – Institut Universitaire du Cancer de ToulouseKidwai Memorial Institute of OncologyKoo Foundation Sun Yat-Sen Cancer CenterMUSC Hollings Cancer CenterNational Cancer Center Hospital EastNational Cancer Centre SingaporeNational Institute of Oncology, HungaryNCT/UCC Dresden – University Hospital Carl Gustav CarusNRG OncologyO'Neal Comprehensive Cancer Center at UABOcean Road Cancer InstitutePhilippine General HospitalPrince of Wales Hospital / Chinese University of Hong KongQIMR Berghofer Medical Research InstituteQST Hospital (National Institutes for Quantum Science and Technology)Queen Mary Hospital / University of Hong KongRajiv Gandhi Cancer Institute and Research CentreShandong Cancer Hospital and InstituteShizuoka Cancer CenterSiriraj Hospital, Mahidol UniversitySun Yat-sen University Cancer CenterTata Medical Center, KolkataTata Memorial CentreTianjin Medical University Cancer Institute and HospitalTROG Cancer ResearchUC San Diego Moores Cancer CenterUMC Utrecht Cancer CenterUniversity of Chicago Medicine Comprehensive Cancer CenterUniversity of Malaya Medical CentreUPMC Hillman Cancer CenterVelindre Cancer CentreVietnam National Cancer Hospital (K Hospital)Zhejiang Cancer Hospital

pathways

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Cancer neuroscience (nerve–tumour signalling)Field cancerisationInvasion: proteases, adhesion & the invasive frontNotch signallingOncogenic viruses

terms

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Alcohol-attributable cancerChemoradiation (chemoradiotherapy, CRT)Combined positive score (CPS)Dose-dense and metronomic chemotherapyDysphagia (difficulty swallowing)Epstein-Barr virus (EBV) in cancerFeeding tube (gastrostomy, PEG, jejunostomy)Head and neck subsites (oral cavity, oropharynx, larynx)HPV status (HPV-positive / HPV-negative)HPV-positive (p16) head and neck cancerInduction therapyLGR5Neoadjuvant / adjuvant / perioperativeNutrition impact symptomsOrgan preservation (watch-and-wait, bladder-sparing, larynx preservation)Perineural invasion (PNI)Re-irradiationSquamous cell carcinomaSquamous cell carcinoma (SCC)TNM staging

trials

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CheckMate 141EXTREMEFORTIFI-HN01JAVELIN Head and Neck 100JUPITER-02KEN SHE (single-dose HPV vaccine)KEYNOTE-048KEYNOTE-689LiGeR-HN1NRG-HN002 & NRG-HN005 (HPV+ de-escalation)RTOG 0129 (HPV analysis)TrilynX

pairings

3
Caution: de-escalating radiation on HPV status aloneEGFR-directed bispecific + PD-1 blockadeImmunotherapy before surgery rather than with chemoradiation (HNSCC)

roadmaps

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Immunotherapy roadmap: Coley's toxins → checkpoint inhibitors → engineered immunity

ideas

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A coordinated FLASH radiotherapy evidence programme with shared dose-rate standardsA dietitian in every gastrointestinal and head and neck tumour boardA funded programme of organ-preservation trials to avoid radical surgeryA platform trial of very-low-cost metronomic chemotherapy in LMIC common cancersA pragmatic trial network for intraoperative margin tools, paid on margin reductionA short pre-surgery drug window as the default early test of new agentsA standing platform for testing new drugs with radiotherapyAn Epstein-Barr virus vaccine to prevent nasopharyngeal cancer and lymphomasBlended finance and a low-cost linac to close the global radiotherapy gapBlood EBV DNA screening for nasopharyngeal cancer across southern China and Southeast AsiaBurden-matched funding for trials led in low- and middle-income countriesCatch-up HPV vaccination for men to prevent throat cancerClear the suppressive neutrophils out of pancreatic tumours firstCommunity health workers with smartphone AI screen for mouth cancer in South AsiaCommunity-tailored HPV vaccine confidence campaigns with school-based deliveryConfirm ultra-low-dose immunotherapy so it can be afforded where most patients livectHPV-DNA-adapted de-escalation of chemoradiationCut the nerve supply to tumours with old drugsEliminate infection-caused cancers: HPV, hepatitis B and C, H. pylori and EBVEvaluate alcohol minimum unit pricing against cancer incidenceIntercept cancer at the field stageKeep dormant cells asleep instead of trying to kill themMake a two-minute mouth cancer check part of every dental visitPhotobiomodulation and a taste and swallowing programme for mouth and throat toxicityPhotoimmunotherapy as an in situ vaccine with PD-1 blockadePre-surgery platform trials that test combinations on pathological response in monthsProtect hearing from cisplatin in adults as we now do in childrenRadiotherapy for everyone who needs it by 2040Real-time margin assessment and image-guided surgery as the global standardStanding reflex biomarker panels per tumour type, run without an oncologist's orderSwitch every country to single-dose HPV vaccination and add catch-up to age 26Treat the draining lymph node before removing itTurn one tumour into a vaccine to treat all the othersTwo-week pre-operative windows to compare combination biology head to headValidate low-cost metronomic oral regimens in phase 3 and carry them into guidelines

people

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Beatriz CasteloCharu AggarwalChristine H. ChungChristophe Le TourneauDeborah Watkins BrunerDenise A. GallowayDouglas R. LowyEverett E. VokesHarald zur HausenHye Ryun KimJohn V. HeymachJun MaKevin HarringtonKumar PrabhashLi ZhangLillian L. SiuMarco GuzzoMu-Sheng ZengMyung-Ju AhnPankaj ChaturvediUlrich KeilholzVanita NoronhaVijay PatilWenfeng Fang

bottlenecks

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Cachexia, toxicity and the limits of the patientFragmented care and guideline gapsMost of the world has almost no cancer careNo one can predict who responds to immunotherapyPrevention we already have is not deployed

key papers

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Alcohol caused an estimated 741,000 cancers worldwide in 2020Fifty years of the British Doctors Study: smokers lose ten years of life, quitting gives most of it backKEYNOTE-048: pembrolizumab, alone or with chemotherapy, as first treatment for recurrent or metastatic head and neck cancerSwedish registry study: HPV vaccination almost eliminates cervical cancer when given before 17