{"entity":{"id":"oropharyngeal-cancer","kind":"cancer","name":"Oropharyngeal cancer (tonsil and base of tongue)","aka":["Oropharynx cancer","Tonsil cancer","Base of tongue cancer","HPV-positive head and neck cancer"],"tldr":"Cancer of the tonsils and back of the tongue, a head and neck cancer, 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.","summary":"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.","asOf":"2026-09-17","wikipedia":"https://en.wikipedia.org/wiki/Oropharyngeal_cancer","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Oropharyngeal_cancer"}],"tags":["subtype-page"],"related":["hpv-negative-head-and-neck-cancer","laryngeal-cancer","oral-cavity-cancer","recurrent-metastatic-hnscc"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["de-escalate","orator"],"people":[],"bottlenecks":[],"keyPapers":["paper-keynote-048-lancet-2019","paper-ang-hpv-oropharyngeal-nejm-2010","paper-rtog-1016-lancet-2019","paper-checkmate-141-ferris-nejm-2016"],"journals":[],"dependsOn":[],"notes":[],"group":"head and neck","burden":"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.","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":["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)"],"standardOfCare":[{"setting":"Diagnosis and staging","approach":"Examination and biopsy with p16 and HPV testing, PET-CT, and separate staging for HPV-positive disease.","refs":["hpv-testing"]},{"setting":"Early disease","approach":"Transoral robotic or laser surgery with neck dissection, or radiotherapy alone, chosen by expected function.","refs":["tors","imrt-igrt"]},{"setting":"Locally advanced disease","approach":"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.","refs":["cisplatin","cetuximab","rtog-1016","de-escalate","bonner-cetuximab-rt"]},{"setting":"Recurrent or metastatic","approach":"Pembrolizumab alone for PD-L1-positive disease or with platinum-fluorouracil (KEYNOTE-048); nivolumab after platinum (CheckMate 141).","refs":["pembrolizumab","nivolumab","keynote-048","checkmate-141"]},{"setting":"Prevention","approach":"HPV vaccination of girls and boys; smoking cessation.","refs":["hpv-vaccine","smoking-cessation-after-diagnosis"]}],"stateOfArt":["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."],"history":[{"year":2000,"title":"HPV linked to oropharyngeal cancer","note":"Gillison and colleagues show HPV16 in a distinct subset of tumours.","refs":[]},{"year":2010,"title":"Ang shows HPV status is the dominant prognostic factor","note":"RTOG 0129 analysis: three-year survival 82 versus 57 percent.","refs":[]},{"year":2017,"title":"Separate staging for HPV-positive disease (AJCC 8th edition)","refs":[]},{"year":2019,"title":"RTOG 1016 and De-ESCALaTE: cetuximab inferior to cisplatin","refs":["rtog-1016","de-escalate"]},{"year":2019,"title":"Pembrolizumab first line in recurrent disease (KEYNOTE-048)","refs":["keynote-048"]}],"pipeline":["de-escalate","adaptive-radiotherapy","hpv-vaccine"],"openProblems":["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."],"parent":"head-and-neck"},"route":"/cancers/oropharyngeal-cancer/","neighbours":{"cancer":[{"id":"head-and-neck","kind":"cancer","name":"Head and neck squamous cell carcinoma","route":"/cancers/head-and-neck/"},{"id":"hpv-negative-head-and-neck-cancer","kind":"cancer","name":"HPV-negative head and neck squamous cell carcinoma (including HPV-negative oropharyngeal cancer)","route":"/cancers/hpv-negative-head-and-neck-cancer/"},{"id":"hpv-positive-oropharyngeal-cancer","kind":"cancer","name":"HPV-positive oropharyngeal cancer","route":"/cancers/hpv-positive-oropharyngeal-cancer/"},{"id":"hypopharyngeal-cancer","kind":"cancer","name":"Hypopharyngeal cancer","route":"/cancers/hypopharyngeal-cancer/"},{"id":"laryngeal-cancer","kind":"cancer","name":"Laryngeal and hypopharyngeal cancer","route":"/cancers/laryngeal-cancer/"},{"id":"oral-cavity-cancer","kind":"cancer","name":"Oral cavity cancer (mouth and tongue)","route":"/cancers/oral-cavity-cancer/"},{"id":"recurrent-metastatic-hnscc","kind":"cancer","name":"Recurrent or metastatic head and neck squamous cell carcinoma","route":"/cancers/recurrent-metastatic-hnscc/"}],"trial":[{"id":"nct06319963","kind":"trial","name":"A Study to Evaluate Lenti-HPV-07 Immunotherapy Against HPV+ Cervical or Oropharyngeal Cancer","route":"/trials/nct06319963/"},{"id":"bonner-cetuximab-rt","kind":"trial","name":"Bonner trial (cetuximab plus radiotherapy)","route":"/trials/bonner-cetuximab-rt/"},{"id":"checkmate-141","kind":"trial","name":"CheckMate 141","route":"/trials/checkmate-141/"},{"id":"de-escalate","kind":"trial","name":"De-ESCALaTE HPV","route":"/trials/de-escalate/"},{"id":"ecog-e3311","kind":"trial","name":"ECOG-ACRIN E3311","route":"/trials/ecog-e3311/"},{"id":"keynote-048","kind":"trial","name":"KEYNOTE-048","route":"/trials/keynote-048/"},{"id":"nrg-hn002-hn005","kind":"trial","name":"NRG-HN002 & NRG-HN005 (HPV+ de-escalation)","route":"/trials/nrg-hn002-hn005/"},{"id":"orator","kind":"trial","name":"ORATOR","route":"/trials/orator/"},{"id":"pathos","kind":"trial","name":"PATHOS","route":"/trials/pathos/"},{"id":"nct05966194","kind":"trial","name":"RRx-001 for Reducing Oral Mucositis in Patients Receiving Chemotherapy and Radiation for Head and Neck Cancer","route":"/trials/nct05966194/"},{"id":"rtog-1016","kind":"trial","name":"RTOG 1016","route":"/trials/rtog-1016/"},{"id":"nct05312710","kind":"trial","name":"Safety and Efficacy of APG-157 in Head and Neck Cancer","route":"/trials/nct05312710/"}],"paper":[{"id":"paper-checkmate-141-ferris-nejm-2016","kind":"paper","name":"CheckMate 141: nivolumab for recurrent head and neck squamous cell carcinoma after platinum","route":"/key-papers/paper-checkmate-141-ferris-nejm-2016/"},{"id":"paper-de-escalate-lancet-2019","kind":"paper","name":"De-ESCALaTE HPV: radiotherapy plus cisplatin or cetuximab in low-risk HPV-positive oropharyngeal cancer","route":"/key-papers/paper-de-escalate-lancet-2019/"},{"id":"paper-ang-hpv-oropharyngeal-nejm-2010","kind":"paper","name":"Human papillomavirus and survival of patients with oropharyngeal cancer (RTOG 0129)","route":"/key-papers/paper-ang-hpv-oropharyngeal-nejm-2010/"},{"id":"paper-keynote-048-lancet-2019","kind":"paper","name":"KEYNOTE-048: pembrolizumab, alone or with chemotherapy, as first treatment for recurrent or metastatic head and neck cancer","route":"/key-papers/paper-keynote-048-lancet-2019/"},{"id":"paper-rtog-1016-lancet-2019","kind":"paper","name":"NRG Oncology RTOG 1016: radiotherapy plus cetuximab versus cisplatin in HPV-positive oropharyngeal cancer","route":"/key-papers/paper-rtog-1016-lancet-2019/"}],"technology":[{"id":"adaptive-radiotherapy","kind":"technology","name":"Adaptive radiotherapy (online replanning)","route":"/technologies/adaptive-radiotherapy/"},{"id":"rejuv-recon-head-neck","kind":"technology","name":"Head and neck reconstruction: the free flap, and what it gives back","route":"/technologies/rejuv-recon-head-neck/"},{"id":"hpv-vaccine","kind":"technology","name":"HPV & HBV vaccination","route":"/technologies/hpv-vaccine/"},{"id":"hpv-testing","kind":"technology","name":"HPV DNA testing and self-sampling","route":"/technologies/hpv-testing/"},{"id":"imrt-igrt","kind":"technology","name":"IMRT / IGRT (modern external beam)","route":"/technologies/imrt-igrt/"},{"id":"smoking-cessation-after-diagnosis","kind":"technology","name":"Smoking cessation in cancer patients","route":"/technologies/smoking-cessation-after-diagnosis/"},{"id":"rejuv-rehab-swallowing","kind":"technology","name":"Swallowing therapy around head and neck radiotherapy","route":"/technologies/rejuv-rehab-swallowing/"},{"id":"tors","kind":"technology","name":"Transoral robotic surgery (TORS)","route":"/technologies/tors/"}],"drug":[{"id":"cetuximab","kind":"drug","name":"Cetuximab","route":"/drugs/cetuximab/"},{"id":"cisplatin","kind":"drug","name":"Cisplatin","route":"/drugs/cisplatin/"},{"id":"nivolumab","kind":"drug","name":"Nivolumab","route":"/drugs/nivolumab/"},{"id":"pembrolizumab","kind":"drug","name":"Pembrolizumab","route":"/drugs/pembrolizumab/"}],"person":[{"id":"anthony-nichols","kind":"person","name":"Anthony C. Nichols","route":"/people/anthony-nichols/"},{"id":"robert-ferris","kind":"person","name":"Robert L. Ferris","route":"/people/robert-ferris/"}],"term":[{"id":"second-primary-lung-after-chest-radiotherapy","kind":"term","name":"Lung cancer after chest radiotherapy and after alkylating chemotherapy","route":"/terms/second-primary-lung-after-chest-radiotherapy/"}]}}