Cancer of the Oropharynx (including tonsils and base of tongue)

Squamous cell carcinoma of the oropharynx

Over 90% of oropharyngeal cancers are squamous cell carcinoma. The squamous cell carcinomas of the oropharynx caused by the human papilloma virus (hpv) behave somewhat differently from the squamous cell carcinomas of the oropharynx caused by smoking.

How common it is

Using stored tumor samples from the national SEER cancer registries, researchers found that the share of oropharyngeal cancers containing HPV rose from 16% in the late 1980s to 72% in the early 2000s. Over the same period the population rate of HPV-positive cancer rose by 225%, while HPV-negative cancer fell by half as fewer people smoked [1]. A meta-analysis of 134 studies found that about 70% of oropharyngeal cancers in North America are attributable to HPV, mostly HPV-16 [2]. People with HPV-related cancer tend to be younger (often in their 50s), are more often men, and are less likely to have smoked [6]. More information is on the oropharyngeal squamous cell carcinoma and throat cancers pages.

Treatment options

Treatment is planned by a team that usually includes a head and neck surgeon, a radiation oncologist and a medical oncologist, and it follows the National Comprehensive Cancer Network (NCCN) guidelines [7]. In general:

• Early-stage cancer (a small primary tumor with no lymph nodes or a single small node) can be treated with one main treatment: either radiation alone, or surgery through the mouth with removal of the lymph nodes in the neck (neck dissection). Radiation or chemoradiation is added after surgery only if the pathology shows features that raise the risk of recurrence [7, 8].

• More advanced cancer is usually treated with radiation and chemotherapy given at the same time (concurrent chemoradiation), or with surgery followed by radiation, with chemotherapy added when the cancer has spread outside a lymph node or reaches the edge of the removed tissue [7].

Transoral surgery or radiation? Transoral robotic surgery (TORS) removes the tumor through the open mouth, without cutting through the jaw or neck. The ORATOR trial randomly assigned 68 patients with early oropharyngeal cancer to radiation or to TORS with neck dissection. Swallowing-related quality of life at one year was slightly better after radiation, but the difference was smaller than the amount considered clinically meaningful [9]. With longer follow-up the swallowing scores became similar, overall and progression-free survival did not differ, and the side effects were different in kind: more dry mouth, hearing loss and ringing in the ears after radiation, and more pain after surgery [10, 5]. The 2025 American Society of Clinical Oncology (ASCO) guideline on TORS therefore treats the choice as a shared decision that depends on the tumor, the person's priorities and the experience of the treating team [8]. More detail is on the throat tumor treatments page.

Why chemotherapy is given with radiation. The largest pooled analysis of head and neck cancer trials (MACH-NC: 107 randomized trials and 19,805 patients) found that adding chemotherapy at the same time as radiation improved five-year survival by 6.5 percentage points. Chemotherapy given before or after radiation, rather than with it, did not provide the same benefit, and the benefit was smaller in older patients [11]. High-dose cisplatin is the standard drug (see the chemotherapy and immunotherapy and radiation therapy pages).

"De-escalation" for HPV-related cancer. Because HPV-related cancer is so curable, several trials have tested whether lighter treatment could cause fewer long-term side effects without losing cure. So far the results call for caution:

• Two large randomized trials replaced cisplatin with cetuximab, a less toxic-seeming targeted drug. In RTOG 1016 (849 patients), five-year survival was 77.9% with cetuximab and 84.6% with cisplatin, and cancer came back more often with cetuximab [12]. In the De-ESCALaTE trial (334 low-risk patients), cetuximab did not reduce side effects, and two-year survival was 89.4% compared with 97.5% with cisplatin [13]. Cisplatin with radiation remains the standard.

• The ECOG-ACRIN E3311 trial tested transoral surgery followed by a reduced radiation dose (50 Gy instead of 60 Gy) for intermediate-risk patients. Two-year progression-free survival was about 95% with the lower dose, similar to the standard dose [14], and results held up at longer follow-up [15]. This is a phase II trial, so the lower dose is considered an option in selected patients rather than a new standard [7].

Outside a clinical trial, guideline groups advise against reducing treatment intensity on the basis of HPV status alone [8, 7].

Other types of tumors of the oropharynx

Less common types of tumors of the oropharynx include lymphoma, salivary gland, melanoma, thyroid, and other rare tumors.

Lymphoma is the most common of these. It starts in the lymphoid tissue of the tonsils and base of tongue (part of a ring of lymphoid tissue in the throat) and is treated mainly with chemotherapy and sometimes radiation, rather than surgery, so an adequate biopsy that the pathologist can test for lymphoma markers is important. Minor salivary gland cancers can arise in the soft palate and base of tongue, and are usually treated with surgery. Because many different tumors can look alike on examination, the diagnosis always rests on the biopsy.

hpv and p16 in squamous cell carcinoma of the oropharynx

The human papilloma virus (HPV) is a common cause of squamous cell carcinoma (a type of cancer) of the tonsils or base of tongue. It also causes cancer in the female cervix. Several different strains of this virus exist, and are numbered from one to over one hundred at last count, named in order of their identification. Some of the strains, such as HPV-16 and HPV-18, are the types more likely to cause cancer, whereas other strains may cause warts on the skin (such as HPV-1) or benign genital warts (such as HPV-6 and HPV-11). HPV is spread by contact, as opposed to aerosols, but this could be any type of contact in which live virus particles are physically transferred to a tissue in which it can grow.

p16 is different from HPV-16. p16 is a protein that is present in high amounts in cancers involved with HPV, and so it is used as an indicator of HPV presence. p16 is produced in high quantity by HPV infected cells. The presence of p16 does not indicate which strain of HPV is present. The fact that the number 16 is associated with the protein p16 and the 16th strain of HPV is just coincidence. A squamous cell carcinoma of the tonsils or base of tongue may be tested for the protein p16. When p16 is present, it is thought that the cancer is caused by HPV. When p16 is not present, another cause, such as tobacco, is the reason for the cancer.

While squamous cell carcinoma may be caused by smoking or by HPV, the type caused by HPV tends to respond somewhat better to treatment and has a better prognosis overall. Smoking (especially when combined with drinking) is another cause of squamous cell carcinoma of the tonsils and base of tongue, and this type is typically p16 negative. Not uncommonly, a cancer in this area has HPV present in an individual with a smoking history. In this case, whether the smoking or the virus caused the cancer in this scenario is not always obvious. When someone has smoked more than 10 pack years of cigarettes and has a p16 positive oropharyngeal squamous cell carcinoma, the statistical outcome is somewhere between that of the nonsmokers with p16 positive oropharynx squamous cell carcinoma and the smokers with p16 negative oropharynx squamous cell carcinoma.

How p16 and HPV are tested

p16 is tested on the biopsy with a stain called immunohistochemistry. A tumor is called p16-positive when at least 70% of the cancer cells stain strongly [16, 7]. p16 is a very good stand-in for HPV, but not a perfect one. In a pooled analysis of 7,654 patients from 13 European and Canadian cohorts, about 11% of p16-positive cancers turned out to be HPV-negative. Five-year survival was 81% when both tests were positive, compared with 55% when the tumor was p16-positive but HPV-negative and 40% when both were negative [17]. A smaller UK study found a similar gap (77% compared with 33%) [18]. For this reason, the 2025 College of American Pathologists guideline and the NCCN guidelines support confirming HPV directly (by testing for viral DNA or RNA) in some situations, especially for patients considering clinical trials [16, 7].

Staging

Since 2017 the American Joint Committee on Cancer (AJCC, 8th edition) has staged p16-positive and p16-negative oropharyngeal cancer separately. For p16-positive cancer, lymph nodes in the neck count for less than they do in tobacco-related cancer, so many people who would previously have been called stage III or IV are now stage I or II. The change reflects their much better survival, not a smaller tumor [4, 6]. A stage I HPV-related cancer is therefore not directly comparable to a stage I tobacco-related cancer.

HPV, smoking and survival

The landmark study is an analysis of the RTOG 0129 trial, in which all patients received chemoradiation. Three-year overall survival was 82.4% for HPV-positive cancer and 57.1% for HPV-negative cancer, and HPV-positive status lowered the risk of death by 58% after other factors were accounted for. Using HPV status, smoking history (more or less than 10 pack-years) and stage, patients fell into low-, intermediate- and high-risk groups with three-year survival of 93%, 71% and 46% [3]. These risk groups were later confirmed at five years in a separate trial [19] and in a pooled analysis of international trials [20].

Smoking matters on its own. Across two large trials, the risk of cancer progression or death rose by about 1% for each pack-year smoked, whether or not the cancer was p16-positive, and smoking during radiation was linked to worse outcomes [21]. Stopping smoking before and during treatment is one of the few things a patient can do that directly affects the result (see how to quit tobacco).

HPV vaccination

HPV vaccines were first approved to prevent cervical cancer, and the 9-valent vaccine is now approved in the United States to prevent HPV-related oropharyngeal and other head and neck cancers in people aged 9 to 45. A meta-analysis of six studies found that vaccination reduced oral infection with vaccine-type HPV by 46% and with HPV-16 by 80% [22]. Because these cancers usually appear decades after infection, studies showing a direct drop in throat cancer rates are still maturing, but preventing the infection is expected to prevent the cancer.

• Link to a slide presentation on the the American Head and Neck Society website with information for the patient on human papilloma virus (HPV) and head and neck cancers.

• Link to an article on HPV in throat cancer on the ENTHealth website.

• YouTube video explaining why HPV vaccination is needed for boys (as well as girls!) Please vaccinate!

Imaging

Imaging is an important component in the assessment of an oropharyngeal tumor for assessing size, anatomic characteristics, spread of the disease, and response to treatment. Among the options for imaging modalities are plain x-ray, ultrasound, CT, MRI, and PET-CT scanning.

In practice, a CT scan with contrast and/or an MRI of the primary site and neck shows the size of the tumor and the lymph nodes. PET-CT is used for more advanced cancers to look for spread to distant sites such as the lungs and to help find a hidden primary tumor [7]. PET-CT is also the standard way to check the neck about three months after chemoradiation. In the PET-NECK trial of 564 patients, those who had PET-CT surveillance (with surgery only if the scan showed remaining cancer) had the same two-year survival as those who had a planned neck dissection, and far fewer neck operations were needed [23].

Swallowing

Swallowing well is essential for maintaining nutrition as well as keeping the lungs free of infection. A decision faced commonly in the treatment of throat cancer is whether to place a gastric feeding tube (G tube).

Both surgery and radiation affect swallowing, in different ways and on different timelines. Swallowing usually gets worse during radiation and in the weeks after surgery, then improves over the following months. In a prospective study of patients with low- and intermediate-risk cancer at MD Anderson, moderate to severe swallowing difficulty measured on X-ray swallow studies was uncommon and did not differ significantly between primary TORS and primary radiation. It was lowest after surgery alone and higher when radiation or chemoradiation had to be added after surgery [24]. In the ORATOR trial, swallowing scores were similar by five years [5].

Swallowing therapy before and during treatment helps. A speech and swallowing therapist usually sees patients before treatment begins, teaches swallowing exercises to keep the muscles working, and monitors swallowing with a modified barium swallow study when needed [7]. Dry mouth after radiation (xerostomia) also makes swallowing harder. More information is on the swallowing page.

Survival

Kaplan-Meier Survival Curves for Oropharyngeal Squamous Cell Carcinoma. These graphs are for all stages grouped together. Overall survival includes patients who are alive, even if cancer is present and growing or spreading. Disease free survival includes patients who are alive and have no evidence that cancer is growing or spreading. Reference: Ang KK, Harris J, Wheeler R, Weber R, Rosenthal DI, Nguyen-Tân PF, Westra WH, Chung CH, Jordan RC, Lu C, Kim H, Axelrod R, Silverman CC, Redmond KP, Gillison ML. Human papillomavirus and survival of patients with oropharyngeal cancer. N Engl J Med. 2010 Jul 1;363(1):24-35. doi: 10.1056/NEJMoa0912217. Epub 2010 Jun 7. PMID: 20530316; PMCID: PMC2943767.

In that study, three-year overall survival was 82.4% for HPV-positive and 57.1% for HPV-negative cancer, and three-year progression-free survival was 73.7% and 43.4% [3]. In a later trial, five-year overall survival was about 88% in the low-risk group (HPV-positive, light or no smoking), 70% in the intermediate-risk group and 45% in the high-risk group [19]. These numbers come from patients treated on clinical trials and describe groups, not individuals.

Follow-up after treatment

Most recurrences happen within the first two to three years, so follow-up visits with an examination of the throat and neck are most frequent then, with imaging at about three months after treatment and afterward as needed [7]. A newer blood test measures fragments of HPV DNA shed by the tumor into the bloodstream (circulating tumor HPV DNA; see HPV ctDNA testing). In a prospective study of 115 patients, no patient whose test stayed negative had a recurrence, and two positive tests in a row predicted recurrence 94% of the time, a median of about four months before it was confirmed [25]. A commercial version of the test performed similarly in more than 1,000 patients [26]. However, no study has yet shown that finding a recurrence earlier this way helps people live longer, and the 2025 College of American Pathologists guideline advises that the test should not yet direct care outside a clinical trial [16]. It is increasingly used alongside, not instead of, examination and imaging.

Additional links

• Cancer of the tonsils and base of tongue are becoming much more common! Smoking and/or the human papilloma virus (HPV) are the usual causes. This moderately in-depth article on the American Head and Neck Society site provides an overview of this type of cancer.

• Link to the American Cancer Society website with information on oropharynx and oral cavity cancer.

Related pages on this site: neck, larynx, hypopharynx, oral cavity, radiation therapy, chemotherapy and immunotherapy, and feeding tube placement.

Summary

• Most oropharyngeal cancers in the United States are now caused by HPV, and their number has risen sharply since the 1980s [1, 2].

• p16 testing on the biopsy identifies HPV-related cancer, which is staged separately and has much better survival, especially in people who have smoked little or not at all [3, 4].

• Early cancer can be treated with transoral surgery or with radiation, with similar survival and different side effects; the choice is a shared decision [5, 8].

• Advanced cancer is usually treated with chemoradiation, or surgery followed by radiation; cisplatin remains the standard drug, and reduced-intensity treatment belongs in clinical trials for now [11, 12, 13].

• Swallowing therapy, dental care, nutrition support and stopping smoking all improve the course of treatment [7, 21].

References

1. Chaturvedi AK, Engels EA, Pfeiffer RM, et al. Human papillomavirus and rising oropharyngeal cancer incidence in the United States. J Clin Oncol. 2011;29(32):4294-301. doi:10.1200/JCO.2011.36.4596 PubMed 21969503

2. Lu Y, Clifford GM, Fairley CK, et al. Human papillomavirus and p16(INK4a) in oropharyngeal squamous cell carcinomas: A systematic review and meta-analysis. Int J Cancer. 2024;154(5):830-841. doi:10.1002/ijc.34763 PubMed 37861207

3. Ang KK, Harris J, Wheeler R, et al. Human papillomavirus and survival of patients with oropharyngeal cancer. N Engl J Med. 2010;363(1):24-35. doi:10.1056/NEJMoa0912217 PubMed 20530316

4. Machczyński P, Majchrzak E, Niewinski P, et al. A review of the 8th edition of the AJCC staging system for oropharyngeal cancer according to HPV status. Eur Arch Otorhinolaryngol. 2020;277(9):2407-2412. doi:10.1007/s00405-020-05979-9 PubMed 32342197

5. Nichols AC, Theurer J, Prisman E, et al. Radiotherapy Versus Transoral Robotic Surgery for Oropharyngeal Squamous Cell Carcinoma: Final Results of the ORATOR Randomized Trial. J Clin Oncol. 2024;42(34):4023-4028. doi:10.1200/JCO.24.00119 PubMed 39303189

6. Chow LQM. Head and Neck Cancer. N Engl J Med. 2020;382(1):60-72. doi:10.1056/NEJMra1715715 PubMed 31893516

7. National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology: Head and Neck Cancers. Version 2.2026. nccn.org

8. Holsinger FC, Ismaila N, Adkins DR, et al. Transoral Robotic Surgery in the Multidisciplinary Care of Patients With Oropharyngeal Squamous Cell Carcinoma: ASCO Guideline. J Clin Oncol. 2025;43(11):1369-1392. doi:10.1200/JCO-24-02755 PubMed 39933131

9. Nichols AC, Theurer J, Prisman E, et al. Radiotherapy versus transoral robotic surgery and neck dissection for oropharyngeal squamous cell carcinoma (ORATOR): an open-label, phase 2, randomised trial. Lancet Oncol. 2019;20(10):1349-1359. doi:10.1016/S1470-2045(19)30410-3 PubMed 31416685

10. Nichols AC, Theurer J, Prisman E, et al. Randomized Trial of Radiotherapy Versus Transoral Robotic Surgery for Oropharyngeal Squamous Cell Carcinoma: Long-Term Results of the ORATOR Trial. J Clin Oncol. 2022;40(8):866-875. doi:10.1200/JCO.21.01961 PubMed 34995124

11. Lacas B, Carmel A, Landais C, et al. Meta-analysis of chemotherapy in head and neck cancer (MACH-NC): An update on 107 randomized trials and 19,805 patients, on behalf of MACH-NC Group. Radiother Oncol. 2021;156:281-293. doi:10.1016/j.radonc.2021.01.013 PubMed 33515668

12. Gillison ML, Trotti AM, Harris J, et al. Radiotherapy plus cetuximab or cisplatin in human papillomavirus-positive oropharyngeal cancer (NRG Oncology RTOG 1016): a randomised, multicentre, non-inferiority trial. Lancet. 2019;393(10166):40-50. doi:10.1016/S0140-6736(18)32779-X PubMed 30449625

13. Mehanna H, Robinson M, Hartley A, et al. Radiotherapy plus cisplatin or cetuximab in low-risk human papillomavirus-positive oropharyngeal cancer (De-ESCALaTE HPV): an open-label randomised controlled phase 3 trial. Lancet. 2019;393(10166):51-60. doi:10.1016/S0140-6736(18)32752-1 PubMed 30449623

14. Ferris RL, Flamand Y, Weinstein GS, et al. Phase II Randomized Trial of Transoral Surgery and Low-Dose Intensity Modulated Radiation Therapy in Resectable p16+ Locally Advanced Oropharynx Cancer: An ECOG-ACRIN Cancer Research Group Trial (E3311). J Clin Oncol. 2022;40(2):138-149. doi:10.1200/JCO.21.01752 PubMed 34699271

15. Burtness B, Flamand Y, Quon H, et al. Long-Term Follow-Up of E3311, an ECOG-ACRIN Cancer Research Group Phase II Trial of Transoral Surgery and Risk-Based Adjuvant Treatment in Human Papillomavirus-Initiated Oropharynx Cancer. J Clin Oncol. 2025;43(23):2559-2565. doi:10.1200/JCO-24-02550 PubMed 40493877

16. Lewis JS Jr, Beadle B, Bishop JA, et al. Human Papillomavirus Testing in Head and Neck Carcinomas: Guideline Update. Arch Pathol Lab Med. 2025;149(6):e115-e150. doi:10.5858/arpa.2024-0388-CP PubMed 40126379

17. Mehanna H, Taberna M, von Buchwald C, et al. Prognostic implications of p16 and HPV discordance in oropharyngeal cancer (HNCIG-EPIC-OPC): a multicentre, multinational, individual patient data analysis. Lancet Oncol. 2023;24(3):239-251. doi:10.1016/S1470-2045(23)00013-X PubMed 36796393

18. Craig SG, Anderson LA, Schache AG, et al. Recommendations for determining HPV status in patients with oropharyngeal cancers under TNM8 guidelines: a two-tier approach. Br J Cancer. 2019;120(8):827-833. doi:10.1038/s41416-019-0414-9 PubMed 30890775

19. Fakhry C, Zhang Q, Gillison ML, et al. Validation of NRG oncology/RTOG-0129 risk groups for HPV-positive and HPV-negative oropharyngeal squamous cell cancer: Implications for risk-based therapeutic intensity trials. Cancer. 2019;125(12):2027-2038. doi:10.1002/cncr.32025 PubMed 30913305

20. Lassen P, Lacas B, Pignon JP, et al. Prognostic impact of HPV-associated p16-expression and smoking status on outcomes following radiotherapy for oropharyngeal cancer: The MARCH-HPV project. Radiother Oncol. 2018;126(1):107-115. doi:10.1016/j.radonc.2017.10.018 PubMed 29100700

21. Gillison ML, Zhang Q, Jordan R, et al. Tobacco smoking and increased risk of death and progression for patients with p16-positive and p16-negative oropharyngeal cancer. J Clin Oncol. 2012;30(17):2102-11. doi:10.1200/JCO.2011.38.4099 PubMed 22565003

22. Tsentemeidou A, Fyrmpas G, Stavrakas M, et al. Human Papillomavirus Vaccine to End Oropharyngeal Cancer. A Systematic Review and Meta-Analysis. Sex Transm Dis. 2021;48(9):700-707. doi:10.1097/OLQ.0000000000001405 PubMed 34110733

23. Mehanna H, Wong WL, McConkey CC, et al. PET-CT Surveillance versus Neck Dissection in Advanced Head and Neck Cancer. N Engl J Med. 2016;374(15):1444-54. doi:10.1056/NEJMoa1514493 PubMed 27007578

24. Hutcheson KA, Warneke CL, Yao CMKL, et al. Dysphagia After Primary Transoral Robotic Surgery With Neck Dissection vs Nonsurgical Therapy in Patients With Low- to Intermediate-Risk Oropharyngeal Cancer. JAMA Otolaryngol Head Neck Surg. 2019;145(11):1053-1063. doi:10.1001/jamaoto.2019.2725 PubMed 31556933

25. Chera BS, Kumar S, Shen C, et al. Plasma Circulating Tumor HPV DNA for the Surveillance of Cancer Recurrence in HPV-Associated Oropharyngeal Cancer. J Clin Oncol. 2020;38(10):1050-1058. doi:10.1200/JCO.19.02444 PubMed 32017652

26. Berger BM, Hanna GJ, Posner MR, et al. Detection of Occult Recurrence Using Circulating Tumor Tissue Modified Viral HPV DNA among Patients Treated for HPV-Driven Oropharyngeal Carcinoma. Clin Cancer Res. 2022;28(19):4292-4301. doi:10.1158/1078-0432.CCR-22-0562 PubMed 35576437