HPV & Oropharyngeal Cancer - What do We Know?
by Dr. C.H. Weaver M.D. updated 6/2020
Oropharyngeal cancer is a type of head and neck cancer. The oropharynx is the part of the throat that includes the soft palate, the base of the tongue, and the tonsils. Exposures that are known to increase the risk of oropharyngeal cancer include tobacco and alcohol use, as well as infection with high-risk types of human papillomavirus (HPV).
- Keep Current With The CancerConnect Newsletter
- Connect With Others In The Cancer Community To Share Information And Support
You may have heard about HPV’s role in cervical cancer, but what about head and neck cancer?
Use this quiz to test your knowledge about this group of viruses.
How many types of HPV are there?
- more than 100
What health conditions are linked with HPV infection?
- cervical cancer
- some head and neck cancers
- all of the above and more
The correct answers are D (more than 100) and D (all of the above and more). Some types of HPV cause warts, and other types of HPV have been linked with cancer. Much of the research on HPV and cancer has focused on HPV’s role in cancers of the cervix, vulva, and vagina, but HPV also contributes to cancers of the penis, anus, and oropharynx (the part of the throat that includes the tonsils, the base of the tongue, and the soft palate).(1)
The HPV infections that cause genital cancers are transmitted sexually. Infection is extremely common and generally occurs soon after an individual becomes sexually active. Many infections clear up on their own, but others persist and increase the risk of cancer.
Sexual transmission may also play an important role in HPV-related oropharyngeal cancers. In this case it is oral HPV infection that increases the risk of cancer. It’s still not completely clear how oral HPV infection occurs, but evidence suggests that oral sex and open-mouthed kissing may play a role.(2) The good news is that the same vaccines that reduce the risk of HPV-related genital cancer may also substantially reduce the risk of HPV-related oropharyngeal cancer.
HPV-related Head and Neck Cancer
Head and neck cancers originate in the tissues in or around the nose, mouth, and throat. Smoking and alcohol use have long been known to increase the risk of head and neck cancer, but more recently it’s become apparent that some cases of head and neck cancer—particularly oropharyngeal cancer—are linked with HPV infection.
It’s still uncertain how many cases of oropharyngeal cancer are due to HPV infection, but researchers have estimated that more than 7,000 cases of HPV-related oropharyngeal and oral cavity cancer occur each year in the United States. In addition, an analysis of studies from around the world reported that 36 percent of oropharyngeal cancers contained HPV. By far the most common type of HPV detected was HPV type 16.(3,4)
In a study published in the New England Journal of Medicine, individuals with oral HPV 16 infections were more than 14 times more likely to have oropharyngeal cancer than uninfected individuals. A greater number of sexual partners—particularly oral-sex partners—was also linked with an increased risk of oropharyngeal cancer.(5)
Trends in the incidence of head and neck cancer provide additional support for a link between HPV and oropharyngeal cancer. Overall the incidence of head and neck cancers has decreased as smoking rates have declined. Incidence of oropharyngeal cancer has not declined, however, and appears to be increasing in young adults.(6)
An interesting observation about HPV-related oropharyngeal cancers is that they appear to have a better prognosis than oropharyngeal cancers due to smoking or other causes. A study of patients with Stage III or IV oropharyngeal cancer was presented at the 2009 Annual Meeting of the American Society of Clinical Oncology. Two-year overall survival was 88 percent among patients with HPV-positive cancers but only 66 percent among patients with HPV-negative cancers. Information about HPV status may eventually influence head and neck cancer treatment decisions.(7)
As more evidence regarding HPV-related oropharyngeal cancer has emerged, attention has turned to prevention. Though there is limited information about how oral HPV infection occurs, oral sex and open-mouthed kissing may both play a role. Information about a probable link with oral sex is important for adolescents as well as adults in order to encourage safer sexual practices. Reports suggest that oral sex is a common practice among adolescents, who believe it to be safe.(8)
HPV vaccines may offer an additional means of prevention. Though direct evidence of a benefit against oropharyngeal cancer is not yet available, it is possible that vaccination will reduce risk. HPV 16 appears to account for a large majority of HPV-related oropharyngeal cancer, and both of the currently available HPV vaccines protect against this type of HPV.
The take-home message? The reach of HPV extends well beyond cervical cancer, affecting both men and women. Fortunately, as our understanding of HPV-related conditions has expanded, so has our understanding of how to prevent infection. Currently available HPV vaccines do not prevent infection with all types of HPV, but they are likely to substantially reduce the burden of HPV-related disease.
What Does The Research Show?
HPV is Linked with Oropharyngeal Cancer
According to the results of a study published in the New England Journal of Medicine HPV contributes to the development of some oropharyngeal cancers.
To assess the relationship between HPV and oropharyngeal cancer, researchers they compared patients with oropharyngeal cancer to individuals without cancer and found that HPV 16 was detected in 72% of the oropharyngeal cancers and that these individuals were more than 14-times more likely than uninfected individuals to develop oropharyngeal cancer. Individuals with a greater number of sexual partners (particularly oral-sex partners) had an increased risk of developing oropharyngeal cancer. The link with number of sexual partners was particularly strong for oropharyngeal cancers that tested positive for HPV 16.
These results suggest that oral HPV infection increases the risk of oropharyngeal cancer. The researchers note that oral HPV infection is most likely sexually acquired, although transmission through direct mouth-to-mouth contact or other means cannot be ruled out.(5)
Particular HPV 16 Strain Linked to Improved Prognosis for Throat Cancer
HPV-linked oropharyngeal cancer have higher survival and lower recurrence rates compared to those with HPV-negative oropharyngeal cancer. As those patients tend to respond better to treatment, researchers are studying whether patients with HPV-linked oropharyngeal cancer can receive less intensive treatment with good outcomes. The researchers point out, however, that there has been limited research that tracks outcomes for oropharyngeal cancer based on the particular strain of HPV that patients have.
Jose P. Zevallos, MD, MPH, an associate member of UNC Lineberger Cancer Center and his colleagues confirmed earlier findings that patients with oropharyngeal cancer tumors infected with HPV16 had improved overall survival and those infected with any other HPV strain had similar survival rates as patients whose cancer did not have HPV at all.
They found that 71.4 percent of patients with HPV16-linked oropharyngeal cancer lived at least five years. Meanwhile, the five-year survival-rates for patients with other strains of the virus in their tumors, and for patients who were HPV-negative, were lower: 57 percent for patients with other types of HPV and 50 percent for HPV-negative patients.(9)
In another analyses doctors reported that HPV types 16, 33, or 35 were present in 40% of cancerj and that HPV-positive cancers had improved anticancer responses to chemotherapy and chemotherapy plus radiation therapy. At two years overall survival was 95% for patients with HPV-positive cancer compared with only 62% for patients with HPV-negative cancer.(10)
Improved Prognosis With p16 HPV
The presence of HPV 16 is associated with high levels of a protein known as p16. In order to determine the impact of p16 researchers divided patients into three groups based on the presence of HPV16 and p16 in tumor tissue:
- Class 1: HPV16 negative, p16 low (39% of subjects)
- Class 2: HPV16-positive, p16 low (37% of subjects)
- Class 3: HPV16-positive, p16 high (23% of subjects)
Outcomes were best for patients in class 3 (HPV16-positive, p16 high):
- Overall survival was 20% for patients in class 1, 18% for patients in class 2, and 79% for patients in class 3.
- The probability of local cancer recurrence within five years was 45% for patients in class 1, 74% for patients in class 2, and 14% for patients in class 3.
The researchers conclude that oropharyngeal tumors that are HPV16-positive and have high p16 levels have a better prognosis than other oropharyngeal tumors.(11)
HPV Status Linked with Better Survival in Oropharyngeal Cancer
It appears that patients with HPV-related oropharyngeal cancer have better overall survival than those with HPV-negative disease. Results from this Phase III clinical trial were published in The New England Journal of Medicine.
Previous studies have suggested that oropharyngeal cancer that is linked with HPV infection has a better prognosis than oropharyngeal cancer that is linked with other causes such as smoking. This recent study further investigated whether HPV status is associated with prognosis in oropharyngeal cancer.
To evaluate whether HPV status can be predictive of overall survival in oropharyngeal cancer, researchers studied outcomes among 323 patients with Stage III-IV oropharyngeal cancer. The study included 206 patients with HPV-positive disease and 117 with HPV-negative disease. Participants were treated with a combination of radiation therapy and chemotherapy. At a median follow-up of almost five years, the following was observed:
- Patients with HPV-positive disease had better three-year rates of overall survival compared with those with HPV-negative disease (82% versus 57%, respectively).
- Progression-free survival was also better in the HPV-positive group than in the HPV-negative group (74% versus 43%, respectively).
- When other prognostic factors were taking into account—including age, race, disease stage, and tobacco use—patients with HPV-positive disease had a 58% reduction in risk of death compared with the HPV-negative group. (It also was noted that tobacco use “significantly” increased the risk of death.)
The researchers concluded that HPV status appears to be linked with survival in oropharyngeal cancer; specifically, HPV-positive disease may be predictive of better overall survival. These findings may be used to determine risk groups for clinical trials and to select appropriate patients for trials of more intensive therapies.(12)
HPV Vaccination May Help Prevent Oropharyngeal Cancer
Infection with high-risk types of HPV contributes to the development of oropharyngeal cancer, and HPV vaccination of both boys and girls may reduce the occurrence of this disease according to a review published in the journal Cancer.
Vaccines that prevent infection with high-risk types of HPV have the potential to greatly reduce the occurrence of cervical cancer as well as other HPV-related cancers. The HPV vaccine targets HPV types 6 and 11 (which are linked with genital warts) as well as the cancer-associated types 16 and 18.
To build the case for vaccinating both girls and boys against HPV, researchers explored trends in head and neck cancer incidence. The trends suggest that overall, the incidence of head and neck cancer has declined as smoking rates have declined. Incidence of oropharyngeal cancer in particular, however, has not declined and appears to be increasing in young adults. This lack of a decline in oropharyngeal cancer may reflect the role of HPV in this disease.
To achieve the maximum possible reduction in HPV-related oropharyngeal cancer, it will likely be important to vaccinate both girls and boys against HPV. The vaccine has not yet been approved for use in boys, but studies in boys are underway. The researchers conclude: “We encourage the rapid study of the efficacy and safety of these vaccines in males and, if successful, the recommendation of vaccination in young adult and adolescent males.”
The two HPV vaccines that are currently approved in the United States are Gardasil® and Cervarix®.
The U.S. Food and Drug Administration approved GARDASIL9 for the prevention of oropharyngeal and other head and neck cancers caused by HPV Types 16, 18, 31, 33, 45, 52, and 58 in June of 2020. Gardasil was first approved by the U.S. Food and Drug Administration in 2006 and protects against four types of HPV: 6, 11, 16, and 18. Types 16 and 18 are linked with cervical cancer as well as certain other types of cancer, and types 6 and 11 cause most cases of genital warts.
GARDASIL 9 is indicated in females 9 through 45 years of age for the prevention of cervical, vulvar, vaginal, anal, oropharyngeal and other head and neck cancers caused by HPV Types 16, 18, 31, 33, 45, 52, and 58; cervical, vulvar, vaginal, and anal precancerous or dysplastic lesions caused by HPV Types 6, 11, 16, 18, 31, 33, 45, 52, and 58; and genital warts caused by HPV Types 6 and 11.
GARDASIL 9 is indicated in males 9 through 45 years of age for the prevention of anal, oropharyngeal and other head and neck cancers caused by HPV Types 16, 18, 31, 33, 45, 52, and 58; anal precancerous or dysplastic lesions caused by HPV Types 6, 11, 16, 18, 31, 33, 45, 52, and 58; and genital warts caused by HPV Types 6 and 11.
Cervarix was first approved by the FDA in 2009 and protects against two types of HPV: 16 and 18. Cervarix is approved for use in girls between the ages of 10 and 25 years for the prevention of cancer or precancer of the cervix.
As more data become available, these vaccines may be approved for additional purposes or for use in additional populations.
It’s important to keep in mind that these vaccines are intended to prevent infection with certain types of HPV. They do not treat existing HPV infections. As a result, the vaccines are likely to be most effective when given before an individual becomes sexually active. Furthermore, because neither vaccine protects against all high-risk types of HPV, they do not completely eliminate the risk of HPV-related cancer.
- Gillison ML, Chaturvedi AK, Lowy DR. HPV prophylactic vaccines and the potential prevention of noncervical cancers in both men and women. Cancer. 2008;113(10 Suppl):3036-46.
- D’Souza G, Agrawal Y, Halpern J, Bodison S, Gillison ML. Oral sexual behaviors associated with prevalent oral human papillomavirus infection. Journal of Infectious Diseases. 2009;199(9):1263-69.
- Ryerson AB, Peters ES, Coughlin SS, et al. Burden of potentially human papillomavirus-associated cancers of the oropharynx and oral cavity in the US, 1998-2003. Cancer. 2008;113(10 Suppl):2901-9.
- Kreimer AR, Clifford GM, Boyle P, Franceschi S. Human papillomavirus types in head and neck squamous cell carcinomas worldwide: a systematic review. Cancer Epidemiology, Biomarkers, and Prevention. 2005;14(2):467-75.
- D’Souza G, Kreimer AR, Viscidi R, et al. Case-control study of human papillomavirus and oropharyngeal cancer. New England Journal of Medicine. 2007;356(19):1944-56.
- Sturgis EM, Cinciripini PM. Trends in head and neck cancer incidence in relation to smoking prevalence: an emerging epidemic of human papillomavirus-associated cancers? *Cancer.*2007;110(7):1429-35.
- Gillison ML, Harris J, Westraet W, et al. Survival outcomes by tumor human papillomavirus (HPV) status in Stage III-IV oropharyngeal cancer (OPC) in RTOG 0129. Paper presented at: 45th Annual Meeting of the American Society of Clinical Oncology; May 29–June 2, 2009; Orlando, Florida. Abstract #6003.
- Gillison ML. Human papillomavirus-related diseases: oropharynx cancers and potential implications for adolescent HPV vaccination. Journal of Adolescent Health. 2008;43(4 Suppl):S52-S60.
- UNC Health Care and UNC School of Medicine. (2016.) Particular HPV strain linked to improved prognosis for throat cancer. [Press release.] Can be retrieved from here
- Fakhry C, Westra W, Li S, et al. Improved survival of patients with human papillomavirus–positive head and neck squamous cell carcinoma in a prospective clinical trial. Journal of the National Cancer Institute [early online publication]. February 13, 2008. DOI: doi:10.1093/jnci/djn011.
- Weinberger PM, Yu Z, Haffty BG et al. Molecular Classification Identified a Subset of Human Papillomavirus-Associated Oropharyngeal Cancers with Favorable Prognosis. Journal of Clinical Oncology. 2006;24:736-747.
- Ang KK, Harris J, Wheeler R. et al**.** Human papillomavirus and survival of patients with oropharyngeal cancer. The New England Journal of Medicine. 363:24-35. July 1, 2010.