HPV-positive oropharyngeal cancer
Throat 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.
Overview
HPV-positive oropharyngeal squamous cell carcinoma arises in the tonsils and base of tongue when high-risk human papillomavirus, almost always type 16, integrates into the crypt epithelium and its E6 and E7 proteins disable p53 and Rb. Tumours are recognised by strong p16 staining, confirmed by HPV DNA or RNA testing where available, and they present with a neck node and a small primary. The RTOG 0129 analysis by Ang and colleagues in 2010 showed three-year overall survival of 82.4 percent for HPV-positive against 57.1 percent for HPV-negative disease, with smoking history worsening the outlook, and the eighth edition of the staging system gave HPV-positive disease a staging system of its own.
Standard treatment is cisplatin chemoradiation to 70 Gy, or transoral robotic surgery with neck dissection followed by pathology-guided adjuvant treatment for smaller tumours. Two trials that replaced cisplatin with cetuximab to spare toxicity both failed: RTOG 1016 found five-year overall survival of 84.6 percent with cisplatin against 77.9 percent with cetuximab, and De-ESCALaTE found two-year survival of 97.5 against 89.4 percent, so cetuximab is reserved for patients who cannot have cisplatin. The Canadian ORATOR trial found swallowing scores slightly better after radiotherapy than after surgery, so neither route is superior for every patient.
De-escalation has worked only where selection was tight. NRG-HN002 found that 60 Gy with weekly cisplatin met its two-year progression-free survival threshold while 60 Gy alone did not; NRG-HN005 then closed early because the reduced-dose arms had worse progression-free survival than the 70 Gy control. After transoral surgery, however, ECOG-ACRIN E3311 reported two-year progression-free survival of about 95 percent with 50 Gy in intermediate-risk patients, and PATHOS is testing the same approach with swallowing and survival endpoints. Circulating tumour HPV DNA, shown by Chera and colleagues in 2020 to detect recurrence before scans, is now being used to adapt treatment, and HPV vaccination of boys and girls is expected to prevent most future cases.
State of the art
- Cure rates above 80 percent with standard chemoradiation make toxicity, not survival, the main problem, which is why every major trial of the last decade has tried to remove treatment.
- Surgery-first de-escalation (E3311, PATHOS) has held up; radiotherapy-dose de-escalation in the definitive setting (NRG-HN005) has not.
- Circulating tumour HPV DNA is the most promising selector for who can have less and who is relapsing.
Red cards
From the labels and guidelines behind the standard of care. Your team's thresholds win.- Emergency services nowBleeding or bruising
Bleeding that will not stop, black or bloody stools, or unexplained bruising when platelets are expected to be low.
- Emergency services nowHypophysitis or adrenal crisis
Persistent headache with extreme tiredness, nausea, dizziness on standing or low blood pressure. Vomiting, severe weakness or collapse is adrenal crisis.
- Check before combiningFood and drink: Pembrolizumab
No pharmacokinetic interactions expected (antibody). See the irAE guide for toxicity management.
- Check before combiningKidneys: Cisplatin
Dose reduce or avoid for CrCl below 60 (carboplatin is the alternative).
- Good to knowImmune-related endocrinopathies (thyroiditis, hypophysitis)
Immunotherapy can attack hormone-producing glands: most often the thyroid (usually ending in an under-active thyroid needing lifelong tablets), and less often the pituitary (hypophysitis) or adrenal glands, which can be life-threatening if missed.
- Good to knowInfusion reactions, hypersensitivity and extravasation
Reactions around the moment a drug is given: chills, fever or breathlessness from antibodies (infusion reactions), true allergy (hypersensitivity, rarely anaphylaxis), and leakage of a damaging drug into tissue around the vein (extravasation).
See all on the product pages:CetuximabCisplatinPembrolizumab·Printable cards in the navigator
Anatomy and lymph node drainage
- Oral cavity and tongue
- Oropharynx: tonsil, base of tongue (HPV)
- Nasopharynx (EBV)
- Larynx and hypopharynx
- Parotid and other salivary glands
- Thyroid
- Nodes: level I (submandibular)
- Nodes: level II (upper jugular)
- Nodes: level III-IV (jugular)
- Nodes: level V (posterior)
- Nodes: level VI (central, thyroid)
- Nodes: retropharyngeal (nasopharynx)
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.
- Oral cavity and tongueHPV-positive base of tongue cancer · p16-positive but HPV DNA-negative discordant tumours (behave more like HPV-negative disease)
- Oropharynx: tonsil, base of tongue (HPV)HPV-positive tonsil cancer · HPV-positive base of tongue cancer · High-risk HPV-positive disease (heavy smokers, bulky or low neck nodes) · p16-positive but HPV DNA-negative discordant tumours (behave more like HPV-negative disease)
- Nasopharynx (EBV)
- Larynx and hypopharynx
- Parotid and other salivary glands
- Thyroid
- level I (submandibular)
- level II (upper jugular)
- level III-IV (jugular)
- level V (posterior)
- level VI (central, thyroid)
- retropharyngeal (nasopharynx)
Same organ: Oropharyngeal cancer (tonsil and base of tongue), 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), HPV-negative head and neck squamous cell carcinoma (including HPV-negative oropharyngeal cancer), Recurrent or metastatic head and neck squamous cell carcinoma, Hypopharyngeal cancer, Adenoid cystic carcinoma, Salivary duct carcinoma, Mucoepidermoid carcinoma, Oral tongue and floor of mouth cancer, Buccal mucosa and gingivobuccal cancer (oral cancer in India), Lip cancer
Show survival figures (1)
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.
- Now the majority of oropharyngeal cancers in North America and Western Europe, typically in men in their fifties and sixties who never smoked heavily; in the RTOG 0129 analysis three-year survival was 82 percent against 57 percent for HPV-negative disease.
- HPV & HBV vaccinationStandard of care
Nothing recorded yet.
Nothing recorded yet.
Also on OnCo: Symptoms and red flags · Early detection roadmap.
Cases by country
No country-level case numbers. This cancer is not mapped to a GLOBOCAN site.
One section per setting: the options named, what each is for, the trials behind them, the recorded trade-offs and the questions to ask.
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.
Transoral robotic surgery with neck dissection and pathology-guided adjuvant radiotherapy (E3311), or radiotherapy alone; choice by expected swallowing and voice.
Cisplatin chemoradiation to 70 Gy; cetuximab only for patients who cannot have cisplatin, since RTOG 1016 and De-ESCALaTE showed it inferior.
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.
Examination and PET-CT at about three months; circulating tumour HPV DNA is emerging as a blood test for recurrence.
Pembrolizumab alone or with platinum-fluorouracil (KEYNOTE-048); HPV-positive tumours respond at least as well as HPV-negative ones.
HPV vaccination of girls and boys before exposure; catch-up vaccination of men is being argued for.
Subtypes & biomarkers
top- HPV-positive tonsil cancer
- HPV-positive base of tongue cancer
- Low-risk (small primary, limited nodes, light or never smoker) disease eligible for de-escalation trials
- High-risk HPV-positive disease (heavy smokers, bulky or low neck nodes)
- p16-positive but HPV DNA-negative discordant tumours (behave more like HPV-negative disease)
- p16 immunohistochemistry (strong nuclear and cytoplasmic staining in at least 70 percent of cells)
- HPV DNA or E6/E7 RNA in situ hybridisation (confirms p16)
- Smoking pack-years (modifies risk group)
- Circulating tumour HPV DNA (surveillance and adaptive de-escalation)
- PD-L1 combined positive score (recurrent disease)
How often this target appears
- 2000Gillison links HPV16 to a distinct subset of oropharyngeal cancers
- 2010RTOG 0129 analysis: HPV status is the strongest prognostic factor
- 2017Separate staging system for HPV-positive disease (AJCC 8th edition)
- 2019RTOG 1016 and De-ESCALaTE: cetuximab inferior to cisplatin
- 2020Circulating tumour HPV DNA detects recurrence before imaging
- 2021NRG-HN002: 60 Gy with cisplatin acceptable, 60 Gy alone not
- 2022E3311: reduced-dose radiotherapy after transoral surgery
- 2025NRG-HN005 closed: de-escalated chemoradiation arms worse
Dated changes read from the records linked to this cancer: approvals, regulatory steps, reported trials, guideline versions and milestones. Newest first; no date is inferred.
All 15 changes by month →- 2026-09-17This recordHPV-positive oropharyngeal cancerFacts on this page last checked
When this page itself was last checked or edited.
- 2025Trial resultNRG-HN002 & NRG-HN005 (HPV+ de-escalation)NRG-HN002 & NRG-HN005 (HPV+ de-escalation) reported
HN005: de-escalated arms had worse PFS; control 2-year PFS 98%.
- 2025MilestoneNRG-HN002 & NRG-HN005 (HPV+ de-escalation)NRG-HN005 closed: de-escalated chemoradiation arms worse
A milestone in how this cancer is treated.
- 2022Trial resultECOG-ACRIN E3311ECOG-ACRIN E3311 reported
Two-year progression-free survival 96.
- 2022MilestoneECOG-ACRIN E3311E3311: reduced-dose radiotherapy after transoral surgery
A milestone in how this cancer is treated.
- 2021MilestoneNRG-HN002 & NRG-HN005 (HPV+ de-escalation)NRG-HN002: 60 Gy with cisplatin acceptable, 60 Gy alone not
A milestone in how this cancer is treated.
What is in development for HPV-positive oropharyngeal cancer, drawn from the whole corpus: 13 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.
Drugs in phase 3 · 1
Trials under way · 4
- PATHOS · phase 2/3 · Velindre University NHS Trust
- 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-L1 · phase 2/3 · BioNTech SE
- A Phase I/IIa Clinical Trial to Investigate BVAC-E6E7 in Subjects With HPV Positive HNSCC. · phase 1/2 · Cellid Co., Ltd.
- A Study to Evaluate Lenti-HPV-07 Immunotherapy Against HPV+ Cervical or Oropharyngeal Cancer · phase 1/2 · Theravectys S.A.
Trials reported · 5
- NRG-HN002 & NRG-HN005 (HPV+ de-escalation) · phase 2/3 · 2025 · mixed
- De-ESCALaTE HPV · phase 3 · 2019 · negative
- ECOG-ACRIN E3311 · phase 2 · 2022 · positive
- RTOG 0129 (HPV analysis) · phase 3 · 2010 · completed
- RTOG 1016 · phase 3 · 2019 · negative
Combinations being explored · 1
Ideas not yet in a trial · 2
Open problems and what is being done
Which patients can safely have less treatment, and by what test.
Long-term dry mouth, swallowing difficulty and fibrosis in people cured in their fifties.
Whether therapeutic HPV vaccines add to immunotherapy in recurrent disease.
and how the field plans to fix it →What is being done about thisRecurrence and residual diseaseAvailable now- Circulating tumour HPV DNA (ctHPV-DNA)Established
In trialsNothing recorded yet.
Ideas and roadmapsNothing recorded yet.
Also on OnCo: Treatment journeys · Survivorship planner.
HPV vaccination uptake in boys and in countries where the epidemic is beginning.
Trials
topTrials recruiting now
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
Expert centres
topExpert centres
Baltimore · cancer center | United States | 0 | 2,955 | 41,449 | #10 | ||
Philadelphia, PA · consortium | United States | none recorded | 1 | 87 | 2,130 | none recorded | - |
Philadelphia, PA · consortium | United States | none recorded | 1 | 15 | 142 | - | |
Wuhan · hospital | China | none recorded | 0 | 2,478 | 31,527 | - | |
Heidelberg · research institute | Germany | none recorded | 0 | 2,202 | 32,575 | - | |
New Delhi · government | India | none recorded | 0 | 2,028 | 15,043 | - | |
Utrecht · cancer center | Netherlands | none recorded | 0 | 1,422 | 20,323 | - | |
Bethesda, MD · government | United States | none recorded | 0 | 1,312 | 26,262 | - | |
Leiden · university | Netherlands | none recorded | 0 | 1,245 | 16,125 | - | |
Tianjin · cancer center | China | none recorded | 0 | 1,219 | 11,455 | - | |
Hangzhou · cancer center | China | none recorded | 0 | 1,219 | 17,635 | - | |
Beijing · hospital | China | none recorded | 0 | 1,154 | 11,808 | - | |
Pittsburgh, PA · cancer center | United States | 0 | 1,078 | 21,539 | - | ||
Rozzano (Milan) · hospital | Italy | none recorded | 0 | 1,031 | 10,720 | - | |
L'Hospitalet de Llobregat · cancer center | Spain | 0 | 988 | 14,310 | - |
These are the things we can measure; they are not a ranking of quality. Each column is a field on the institution record or a count over what OnCo has linked; a centre that treats many patients with HPV-positive oropharyngeal cancer but is thinly recorded here will look small.
Not known: OnCo holds no case-volume or outcome figures for centres, so none are shown. Where a national audit or registry publishes them, the centre's page links to it. Default order: Newsweek rank, then trials for this cancer, then research output.
Questions to ask
topQuestions to ask your oncologist about HPV-positive oropharyngeal cancer
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, HPV DNA or E6/E7 RNA in situ hybridisation, Smoking pack-years, Circulating tumour HPV DNA, PD-L1 combined positive score), 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-positive tonsil cancer, HPV-positive base of tongue cancer, Low-riskdisease eligible for de-escalation trials.
- 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: 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.
Early disease (small primary, limited nodes)
- For my situation (early disease (small primary, limited nodes)), which of the standard options do you recommend and why?Why: Guideline options include: Transoral robotic surgery with neck dissection and pathology-guided adjuvant radiotherapy (E3311), or radiotherapy alone; choice by expected swallowing and voice.
- How do the results of ECOG-ACRIN E3311 apply to someone like me?Why: Trial populations differ from individual patients; ask how closely you match.
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 to 70 Gy; cetuximab only for patients who cannot have cisplatin, since RTOG 1016 and De-ESCALaTE showed it inferior.
- 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.
De-escalation
- For my situation (de-escalation), which of the standard options do you recommend and why?Why: Guideline options include: 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.
- How do the results of NRG-HN002 & NRG-HN005 (HPV+ de-escalation) and PATHOS apply to someone like me?Why: Trial populations differ from individual patients; ask how closely you match.
Surveillance
- For my situation (surveillance), which of the standard options do you recommend and why?Why: Guideline options include: Examination and PET-CT at about three months; circulating tumour HPV DNA is emerging as a blood test for recurrence.
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 or with platinum-fluorouracil (KEYNOTE-048); HPV-positive tumours respond at least as well as HPV-negative ones.
- 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.
- How do the results of KEYNOTE-048 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 before exposure; catch-up vaccination of men is being argued for.
- Am I a candidate for Nonavalent HPV vaccine, and what side effects should I expect?Why: Knowing the expected toxicities helps you plan work, family, and supportive care.
Any stage
- Are there clinical trials I could join, for example of Circulating tumour HPV DNA (ctHPV-DNA), PATHOS, NRG-HN002 & NRG-HN005 (HPV+ de-escalation), ctHPV-DNA-adapted de-escalation of chemoradiation?Why: 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?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 “Which patients can safely have less treatment, and by what test”. How does that affect my plan?Why: Open problems are where trials and second opinions matter most.
- I read that “Long-term dry mouth, swallowing difficulty and fibrosis in people cured in their fifties”. How does that affect my plan?Why: Open problems are where trials and second opinions matter most.
Newly diagnosed? Read the first 60 days with HPV-positive oropharyngeal cancer, then print the one-page appointment sheet with room for the answers.
Print this page for your appointment (your browser's print command). These prompts are for discussion; your clinical team knows your case.
Direct links plus the targets, companies, and technologies of this cancer's products.
technologies
9targets
2drugs
5companies
3terms
3trials
10pairings
1ideas
2Latest papers
topQuery for this cancer: (TITLE:"HPV-positive oropharyngeal cancer" OR ABSTRACT:"HPV-positive oropharyngeal cancer" OR TITLE:"p16-positive oropharyngeal cancer" OR ABSTRACT:"p16-positive oropharyngeal cancer" OR TITLE:"HPV-associated oropharyngeal squamous cell carcinoma" OR ABSTRACT:"HPV-associated oropharyngeal squamous cell carcinoma" OR TITLE:"HPV-driven throat cancer" OR ABSTRACT:"HPV-driven throat cancer") AND (treatment OR therapy OR trial OR survival OR diagnosis). Results are unfiltered search hits about HPV-positive oropharyngeal cancer, not a curated reading list.
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