Oropharyngeal cancer (tonsil and base of tongue)

aka Oropharynx cancer, Tonsil cancer, Base of tongue cancer, HPV-positive head and neck cancer

Cancer of the tonsils and back of the tongue now comes mostly from HPV infection rather than smoking, and behaves like a different disease: it responds well to chemoradiation, most patients are cured, and the research question is how much treatment can safely be removed.

Part of Head and neck squamous cell carcinoma

Oropharyngeal squamous cell carcinoma arises in the tonsils, base of tongue, soft palate and pharyngeal wall. In North America and Europe most cases are now caused by HPV type 16 and are staged separately because they carry a far better outlook than tobacco-related, HPV-negative tumours, which are more often p53-mutant and resistant. Standard treatment is cisplatin chemoradiation, or transoral robotic surgery with neck dissection and adjuvant treatment for smaller tumours; cetuximab proved inferior to cisplatin in HPV-positive disease in RTOG 1016 and De-ESCALaTE. Trials are testing lower radiotherapy doses, fewer drugs and circulating HPV DNA to guide de-escalation in HPV-positive patients, while HPV vaccination is expected to prevent most future cases. Recurrent or metastatic disease is treated with pembrolizumab, alone or with chemotherapy, on KEYNOTE-048.

State of the art

HPV-positive oropharyngeal cancer has an eighth-edition staging system of its own because its survival is so much better.
De-escalation is the frontier: reduced-dose radiotherapy after induction or surgery, and circulating HPV DNA to pick who can have less, are in phase 2 and 3 trials.
Immunotherapy is standard in recurrent disease and is being tested with chemoradiation in the curative setting.

Anatomy and lymph node drainage

Head and neck, salivary glands and thyroid: subsites and node stations · wireframe schematic, not to scale

Organ atlas →

Site decides cause and behaviour: HPV drives oropharyngeal cancer, EBV drives nasopharyngeal cancer, tobacco drives oral and laryngeal cancer; all drain into the neck node levels that surgeons and radiotherapists map.

Subsites

Oral cavity and tongueHPV-negative (tobacco and alcohol related) oropharyngeal cancer · Base of tongue
Oropharynx: tonsil, base of tongue (HPV)HPV-positive (p16-positive) oropharyngeal cancer · HPV-negative (tobacco and alcohol related) oropharyngeal cancer · Tonsil
Nasopharynx (EBV)
Larynx and hypopharynx
Parotid and other salivary glands
Thyroid

Regional lymph nodes

level I (submandibular)
level II (upper jugular)
level III-IV (jugular)
level V (posterior)
level VI (central, thyroid)
retropharyngeal (nasopharynx)

Same organ: Laryngeal and hypopharyngeal cancer, Oral cavity cancer (mouth and tongue), Head and neck squamous cell carcinoma, Nasopharyngeal carcinoma, Salivary gland cancers, Papillary thyroid cancer, Follicular thyroid cancer, Medullary thyroid cancer, Anaplastic thyroid cancer, Thyroid cancer, Nasal cavity and paranasal sinus cancers (including esthesioneuroblastoma), NUT carcinoma (midline carcinoma with NUTM1 rearrangement), Parathyroid carcinoma, Multiple endocrine neoplasia syndromes (MEN1, MEN2, MEN4)

Who gets it and what has changed

The fastest-rising head and neck cancer in high-income countries, now driven mainly by human papillomavirus in men in their fifties and sixties; HPV-positive disease is cured in most cases, HPV-negative disease in far fewer.

Group

head-and-neck

What is being done about this

Finding cancer earlier

and how the field plans to fix it →

Available now

HPV & HBV vaccinationStandard of care
HPV DNA testing and self-samplingStandard of care
AI in radiologyEstablished
cfDNA fragmentomicsEstablished
Colorectal cancer screening (colonoscopy, FIT, stool DNA, blood)Standard of care
DNA methylation profilingEstablished

In trials

GalleriPhase 3
Kerala oral cancer visual screening trial (Trivandrum)Positive
Multi-cancer early detection (MCED)Phase 3
Mumbai VIA cervical screening trial (Tata Memorial)Positive
NHS-GalleriCompleted
NLST & NELSON (low-dose CT screening)Positive

Ideas and roadmaps

Background: Alpha-fetoprotein (AFP), Barrett's oesophagus, CA 19-9, Early detection, Faecal immunochemical test (FIT). Also on OnCo: Symptoms and red flags · Early detection roadmap.

Cases by country

Cases by country · GLOBOCAN 2022

All countries →

No country-level case numbers. This cancer is not mapped to a GLOBOCAN site.

Standard of care

5top

Lines of therapy by subgroup →Staging and risk scores →

Diagnosis and staging

Examination and biopsy with p16 and HPV testing, PET-CT, and separate staging for HPV-positive disease.

HPV DNA testing and self-sampling

Early disease

Transoral robotic or laser surgery with neck dissection, or radiotherapy alone, chosen by expected function.

Transoral robotic surgery (TORS)IMRT / IGRT (modern external beam)

Locally advanced disease

Cisplatin chemoradiation (70 Gy); cetuximab only for patients who cannot have cisplatin, since RTOG 1016 and De-ESCALaTE showed it inferior in HPV-positive disease.

CisplatinCetuximabRTOG 1016 De-ESCALaTE HPV Bonner trial (cetuximab plus radiotherapy)

Recurrent or metastatic

Pembrolizumab alone for PD-L1-positive disease or with platinum-fluorouracil (KEYNOTE-048); nivolumab after platinum (CheckMate 141).

PembrolizumabNivolumabKEYNOTE-048 CheckMate 141

Prevention

HPV vaccination of girls and boys; smoking cessation.

HPV & HBV vaccination Smoking cessation in cancer patients

Subtypes & biomarkers

top

Subtypes

HPV-positive (p16-positive) oropharyngeal cancer
HPV-negative (tobacco and alcohol related) oropharyngeal cancer
Tonsil
Base of tongue
Soft palate and pharyngeal wall

Biomarkers clinicians test

p16 immunohistochemistry and HPV DNA or RNA
Smoking history (worsens HPV-positive outlook)
Circulating HPV DNA (surveillance and de-escalation trials)
PD-L1 combined positive score (recurrent disease)
TP53 mutation (HPV-negative)

How often this target appears

History

5top

2000HPV linked to oropharyngeal cancer
Gillison and colleagues show HPV16 in a distinct subset of tumours.
2010Ang shows HPV status is the dominant prognostic factor
RTOG 0129 analysis: three-year survival 82 versus 57 percent.
2017Separate staging for HPV-positive disease (AJCC 8th edition)
2019RTOG 1016 and De-ESCALaTE: cetuximab inferior to cisplatin
RTOG 1016 De-ESCALaTE HPV
2019Pembrolizumab first line in recurrent disease (KEYNOTE-048)
KEYNOTE-048

In development

0top

What is in development for Oropharyngeal cancer (tonsil and base of tongue), drawn from the whole corpus: 0 items. Drugs are grouped by the most advanced trial phase they have reached anywhere; approved treatments sit under standard of care. Technologies are the methods being tested for this cancer, trials are the studies recorded here, and ideas are proposals not yet in a trial.

Nothing recorded in development for this cancer yet.

Open problems and what is being done

How far treatment can be reduced in HPV-positive disease without losing cures.
HPV-negative oropharyngeal cancer still has poor outcomes.
Long-term swallowing and dry mouth after chemoradiation.
HPV vaccination uptake in boys and in low-income countries.

Trials

top

Trials recruiting now

Recruiting trials near you · live from ClinicalTrials.gov

Oropharyngeal cancer (tonsil and base of tongue)

condition: Oropharyngeal cancer

Open on ClinicalTrials.gov →

within

Country and place are remembered in this browser only. A postcode is sent to OpenStreetMap's Nominatim service to find coordinates when you press the button; nothing else leaves your device.

Landmark trials

Bonner trial (cetuximab plus radiotherapy)CheckMate 141 De-ESCALaTE HPV KEYNOTE-048 RTOG 1016

Expert centres

top

Where the expertise is

Expert centres

Johns Hopkins Hospital / Sidney Kimmel Comprehensive Cancer CenterBaltimore, USNewsweek oncology #10NCI comprehensive
via Pembrolizumab
Charlotte Maxeke Johannesburg Academic Hospital / University of the WitwatersrandJohannesburg, ZA
via IMRT / IGRT (modern external beam), HPV & HBV vaccination
ICMR-National Institute of Cancer Prevention and ResearchNoida, IN
via HPV DNA testing and self-sampling, HPV & HBV vaccination
Institut National d'Oncologie, RabatRabat, MA
via IMRT / IGRT (modern external beam), HPV & HBV vaccination
Institute of Oncology LjubljanaLjubljana, SI
via IMRT / IGRT (modern external beam), HPV & HBV vaccination
Kenyatta National HospitalNairobi, KE
via IMRT / IGRT (modern external beam), HPV & HBV vaccination
Ocean Road Cancer InstituteDar es Salaam, TZ
via IMRT / IGRT (modern external beam), HPV & HBV vaccination
University of New Mexico Comprehensive Cancer CenterAlbuquerque, NM, USNCI comprehensive
via HPV DNA testing and self-sampling, HPV & HBV vaccination
Aarhus University HospitalAarhus, DK
via IMRT / IGRT (modern external beam)
Advanced Centre for Treatment, Research and Education in CancerNavi Mumbai, IN
via Nivolumab
All India Institute of Medical Sciences, New DelhiNew Delhi, IN
via HPV & HBV vaccination
Alliance for Clinical Trials in OncologyChicago, IL, US
via Pembrolizumab
American Society for Radiation OncologyArlington, VA, US
via IMRT / IGRT (modern external beam)
BC CancerVancouver, BC, CA
via HPV DNA testing and self-sampling
Cancer Institute (WIA), AdyarChennai, IN
via HPV & HBV vaccination
Catalan Institute of Oncology (ICO)L'Hospitalet de Llobregat, ES
via HPV & HBV vaccination
Centre Antoine LacassagneNice, FR
via IMRT / IGRT (modern external beam)
Centre Oscar LambretLille, FR
via IMRT / IGRT (modern external beam)
Children's Cancer Hospital Egypt 57357Cairo, EG
via IMRT / IGRT (modern external beam)
Comprehensive Cancer Center Freiburg (CCCF)Freiburg im Breisgau, DE
via IMRT / IGRT (modern external beam)
Dartmouth Cancer CenterLebanon, NH, USNCI comprehensive
via Nivolumab
Department of Biotechnology, Government of IndiaNew Delhi, IN
via HPV & HBV vaccination
Dharmais National Cancer CenterJakarta, ID
via HPV & HBV vaccination
European Cancer OrganisationBrussels, BE
via HPV & HBV vaccination
European Society for Radiotherapy and OncologyBrussels, BE
via IMRT / IGRT (modern external beam)
Gates FoundationSeattle, WA, US
via HPV & HBV vaccination
Geneva University Hospitals (HUG)Geneva, CH
via IMRT / IGRT (modern external beam)
German Cancer Research Center (DKFZ)Heidelberg, DE
via HPV & HBV vaccination
German Hodgkin Study GroupCologne, DE
via Nivolumab
GOG FoundationPhiladelphia, PA, US
via Pembrolizumab
Groote Schuur Hospital / University of Cape TownCape Town, ZA
via IMRT / IGRT (modern external beam)
Guy's and St Thomas' NHS Foundation Trust / King's Health Partners Cancer CentreLondon, GB
via IMRT / IGRT (modern external beam)
Hacettepe University Cancer InstituteAnkara, TR
via IMRT / IGRT (modern external beam)
Hamad Medical Corporation / National Center for Cancer Care and ResearchDoha, QA
via IMRT / IGRT (modern external beam)
Ho Chi Minh City Oncology HospitalHo Chi Minh City, VN
via IMRT / IGRT (modern external beam)
Hokkaido University HospitalSapporo, JP
via IMRT / IGRT (modern external beam)
Hospital de Amor (Barretos Cancer Hospital)Barretos, BR
via HPV & HBV vaccination
Hunan Cancer HospitalChangsha, CN
via IMRT / IGRT (modern external beam)
Indiana University Melvin and Bren Simon Comprehensive Cancer CenterIndianapolis, IN, USNCI comprehensive
via Cisplatin
Institut BergoniéBordeaux, FR
via IMRT / IGRT (modern external beam)
Institut Jules BordetBrussels, BE
via Pembrolizumab
Institut PasteurParis, FR
via HPV & HBV vaccination
Institut Salah AzaïezTunis, TN
via IMRT / IGRT (modern external beam)
Instituto Nacional de Câncer (INCA)Rio de Janeiro, BR
via HPV & HBV vaccination
Instituto Nacional de Cancerología (Colombia)Bogotá, CO
via HPV & HBV vaccination
Instituto Nacional de Cancerología (Mexico)Mexico City, MX
via HPV & HBV vaccination
Instituto Nacional de Enfermedades NeoplásicasLima, PE
via HPV & HBV vaccination
Instituto Português de Oncologia de Lisboa Francisco GentilLisbon, PT
via IMRT / IGRT (modern external beam)
International Atomic Energy Agency: Rays of HopeVienna, AT
via IMRT / IGRT (modern external beam)
International Extranodal Lymphoma Study GroupBellinzona, CH
via IMRT / IGRT (modern external beam)
IRCCS Humanitas Research HospitalRozzano (Milan), IT
via IMRT / IGRT (modern external beam)
Istanbul University Institute of OncologyIstanbul, TR
via IMRT / IGRT (modern external beam)
Istituto Nazionale Tumori IRCCS Fondazione G. PascaleNaples, IT
via Nivolumab
IUCT Oncopole (Institut Universitaire du Cancer de Toulouse)Toulouse, FR
via IMRT / IGRT (modern external beam)
Juravinski Cancer Centre / Escarpment Cancer Research InstituteHamilton, ON, CA
via IMRT / IGRT (modern external beam)
Kaiser Permanente Division of ResearchOakland, CA, US
via HPV & HBV vaccination
Korle Bu Teaching HospitalAccra, GH
via IMRT / IGRT (modern external beam)
Kyoto University HospitalKyoto, JP
via Nivolumab
Lagos University Teaching HospitalLagos, NG
via IMRT / IGRT (modern external beam)
Laura and Isaac Perlmutter Cancer Center at NYU Langone HealthNew York, NY, USNCI comprehensive
via Nivolumab
Lausanne University Hospital (CHUV) / Ludwig Institute LausanneLausanne, CH
via Pembrolizumab
Leeds Cancer Centre, St James's University HospitalLeeds, GB
via IMRT / IGRT (modern external beam)
Leiden University Medical CenterLeiden, NL
via HPV & HBV vaccination
Maria Skłodowska-Curie National Research Institute of OncologyWarsaw, PL
via IMRT / IGRT (modern external beam)
Markey Cancer Center, University of KentuckyLexington, KY, USNCI comprehensive
via HPV & HBV vaccination
Masaryk Memorial Cancer InstituteBrno, CZ
via IMRT / IGRT (modern external beam)
National Cancer Center Hospital EastKashiwa, Chiba, JP
via Nivolumab
National Cancer Institute (NIH)Bethesda, MD, US
via Smoking cessation in cancer patients
National Cancer Institute, Cairo UniversityCairo, EG
via IMRT / IGRT (modern external beam)
National Institute of Oncology, HungaryBudapest, HU
via IMRT / IGRT (modern external beam)
National Taiwan University HospitalTaipei, TW
via HPV & HBV vaccination
NCI Center for Cancer Research (intramural programme)Bethesda, MD, US
via HPV & HBV vaccination
NCT/UCC Dresden, University Hospital Carl Gustav CarusDresden, DE
via IMRT / IGRT (modern external beam)
Oxford Cancer (Oxford University Hospitals and University of Oxford)Oxford, GB
via IMRT / IGRT (modern external beam)
Philippine General HospitalManila, PH
via HPV & HBV vaccination
Rajiv Gandhi Cancer Institute and Research CentreNew Delhi, IN
via IMRT / IGRT (modern external beam)
Rambam Health Care CampusHaifa, IL
via IMRT / IGRT (modern external beam)
Rigshospitalet, Copenhagen University HospitalCopenhagen, DK
via IMRT / IGRT (modern external beam)
Royal Adelaide HospitalAdelaide, AU
via IMRT / IGRT (modern external beam)
Shandong Cancer Hospital and InstituteJinan, CN
via IMRT / IGRT (modern external beam)
Siriraj Hospital, Mahidol UniversityBangkok, TH
via IMRT / IGRT (modern external beam)
Society of Gynecologic OncologyChicago, IL, US
via HPV & HBV vaccination
SWOG Cancer Research NetworkPortland, OR, US
via Nivolumab
Tata Medical Center, KolkataKolkata, IN
via IMRT / IGRT (modern external beam)
Tawam HospitalAl Ain, AE
via IMRT / IGRT (modern external beam)
Tel Aviv Sourasky Medical CenterTel Aviv, IL
via IMRT / IGRT (modern external beam)
Tianjin Medical University Cancer Institute and HospitalTianjin, CN
via IMRT / IGRT (modern external beam)
Tongji Hospital, Huazhong University of Science and TechnologyWuhan, CN
via HPV & HBV vaccination
TROG Cancer ResearchNewcastle, NSW, AU
via IMRT / IGRT (modern external beam)
Uganda Cancer InstituteKampala, UG
via HPV & HBV vaccination
UMC Utrecht Cancer CenterUtrecht, NL
via IMRT / IGRT (modern external beam)
University of Malaya Medical CentreKuala Lumpur, MY
via IMRT / IGRT (modern external beam)
University of Wisconsin Carbone Cancer CenterMadison, WI, USNCI comprehensive
via IMRT / IGRT (modern external beam)
UPMC Hillman Cancer CenterPittsburgh, PA, USNCI comprehensive
via Cetuximab
Velindre Cancer CentreCardiff, GB
via IMRT / IGRT (modern external beam)
Vietnam National Cancer Hospital (K Hospital)Hanoi, VN
via IMRT / IGRT (modern external beam)
West German Cancer Center (WTZ), University Hospital EssenEssen, DE
via Nivolumab
World Health Organization Cancer ProgrammeGeneva, CH
via HPV & HBV vaccination
Zhejiang Cancer HospitalHangzhou, CN
via IMRT / IGRT (modern external beam)

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

top

Bring to your appointment

Questions to ask your oncologist about Oropharyngeal cancer

Generated from this cancer's standard of care, biomarkers, and pipeline · 17 questions

Newly diagnosed

What is my exact diagnosis, stage, and grade, and which tests established them?
Why: Everything else follows from an accurate stage and subtype.
Which biomarkers have been tested on my tumour (for example p16 immunohistochemistry and HPV DNA or RNA, Smoking history, Circulating HPV DNA, PD-L1 combined positive score, TP53 mutation), and what were the results?
Why: These results decide eligibility for targeted therapy, immunotherapy, and trials.
Which subtype is my cancer, and does that change the recommended treatment?
Why: Recognised subtypes for this cancer include HPV-positiveoropharyngeal cancer, HPV-negativeoropharyngeal cancer, Tonsil.
Is germline (inherited) genetic testing recommended for me or my family?
Why: 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?
Why: Guideline options include: Examination and biopsy with p16 and HPV testing, PET-CT, and separate staging for HPV-positive disease.

Early disease

For my situation (early disease), which of the standard options do you recommend and why?
Why: Guideline options include: Transoral robotic or laser surgery with neck dissection, or radiotherapy alone, chosen by expected function.

Locally advanced disease

For my situation (locally advanced disease), which of the standard options do you recommend and why?
Why: Guideline options include: Cisplatin chemoradiation (70 Gy); cetuximab only for patients who cannot have cisplatin, since RTOG 1016 and De-ESCALaTE showed it inferior in HPV-positive disease.
Am I a candidate for Cisplatin, Cetuximab, and what side effects should I expect?
Why: 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?
Why: 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?
Why: Guideline options include: Pembrolizumab alone for PD-L1-positive disease or with platinum-fluorouracil (KEYNOTE-048); nivolumab after platinum (CheckMate 141).
Am I a candidate for Pembrolizumab, Nivolumab, and what side effects should I expect?
Why: Knowing the expected toxicities helps you plan work, family, and supportive care.
How do the results of KEYNOTE-048 and CheckMate 141 apply to someone like me?
Why: 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?
Why: Guideline options include: HPV vaccination of girls and boys; smoking cessation.

Any stage

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.
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.
I read that “How far treatment can be reduced in HPV-positive disease without losing cures”. How does that affect my plan?
Why: Open problems are where trials and second opinions matter most.
I read that “HPV-negative oropharyngeal cancer still has poor outcomes”. 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.

24top

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

Latest papers

top

Connected

15top

Cancer
Laryngeal and hypopharyngeal cancer
Shares KEYNOTE-048, Smoking cessation in cancer patients, Cetuximab, Cisplatin and the tag subtype-page.
Cancer
Oral cavity cancer (mouth and tongue)
Shares KEYNOTE-048, Smoking cessation in cancer patients, Cisplatin, IMRT / IGRT (modern external beam) and the tag subtype-page.
Cancer
Oesophageal squamous cell carcinoma
Shares Smoking cessation in cancer patients, Cisplatin, Nivolumab, Pembrolizumab and the tag subtype-page.
Cancer
Muscle-invasive and advanced bladder cancer
Shares Cisplatin, Nivolumab, IMRT / IGRT (modern external beam), Pembrolizumab and the tag subtype-page.
Cancer
Seminoma
Shares Cisplatin, IMRT / IGRT (modern external beam) and the tag subtype-page.
Cancer
Peritoneal mesothelioma
Shares Nivolumab, Pembrolizumab and the tag subtype-page.
Cancer
Anaplastic thyroid cancer
Shares IMRT / IGRT (modern external beam), Pembrolizumab and the tag subtype-page.
Cancer
Pleural mesothelioma
Shares Nivolumab, Pembrolizumab and the tag subtype-page.

Stay in the loop

Oropharyngeal cancer (tonsil and base of tongue)

State of the art

Anatomy and lymph node drainage

Cases by country

Standard of care

Subtypes & biomarkers

How often this target appears

History

In development

Open problems and what is being done

Trials

Trials recruiting now

Landmark trials