Gloria Wood, BSN, RN
HPV is the most common sexually transmitted disease in the United States and can infect the oropharynx (tonsils and back of throat), anus, and genitals. Many types of HPV exist, with some types having no effect, whereas others cause cancer or warts. Oral HPV infection can lead to HPV-positive oropharyngeal squamous cell cancer after many years.
Researchers have identified over 170 types of HPV, more than 40 of which are typically transmitted through sexual contact. HPV is a DNA virus with over 100 different subtypes that infect the skin and the mucosa, with the most common being HPV 16 and 18.1
Current estimates of the etiology of squamous cell carcinoma of the oropharynx indicate that 84% are related to HPV infection,2 a significant change from the prior decades of tobacco- and alcohol-related cancers.
HPV-related oropharyngeal cancer is now a well-defined entity with recognized risk factors that include young age, good performance status, male gender, nonsmoking and non-drinking status, basaloid tumor histology, and high-risk sexual behavior. The prognosis for these patients is believed to be better than that for patients who have non-HPV oropharyngeal cancer.
Recent reports suggest that HPV infection affects prognosis. Carole Fakhry et al reported the results of a prospective trial that HPV-related oropharyngeal cancer behaves in a different fashion, has a different response to therapy, is more sensitive to radiation-based therapies, and thus may require a different therapeutic approach compared with HPV-unrelated oropharyngeal cancer.3,4
Oropharyngeal Cancer—By the Numbers5
- In 2015, approximately 45,780 people in the US (32,670 men and 13,110 women) will be diagnosed with an oropharyngeal cancer.
- Oropharynx cancer ranks as the eighth most common cancer among men
- An estimated 8650 deaths (6010 men and 2640 women) occurred in the year 2015 from an oropharyngeal cancer
- By 2020, the annual number of HPV-positive oropharyngeal squamous cell carcinomas (OPSCC) (~8700 patients) will surpass the annual number of cervical cancers (~7700 patients) with the majority occurring among men (~7400). By 2030, OPSCC will likely constitute a majority (47%) of all head and neck cancers.
Screening and Prevention of HPVWhile some commercial tests are available in the dental community, the value of this testing as a screening tool is not clear. Testing positive on any given day for oral HPV does not prove persistence of infection. The HPV virus often will clear on its own and not cause any health-related problems.
The human papillomavirus frequently has no symptoms, and therefore it is easily and not knowingly passed from one person to another. At this time no studies have explored how oral HPV can be prevented. However, it is likely that condoms and dental dams, when used consistently and correctly, will lower the chances of giving or getting oral HPV during oral sex. More research is needed to understand how oral HPV is transmitted, how it can be prevented, and who is most likely to develop health problems from an oral HPV infection.
HPV VaccinationAbout 80% of population aged 14-44 have HPV exposure through oral sex with the opposite sex partner.1 The HPV vaccine prevents people from getting new HPV infections specific to the subtypes the vaccine covers. The vaccine will not help to clear an infection that is already present.
Three HPV vaccines have been licensed by the FDA since 2006. CDC recommends these HPV vaccines for routine use among girls and boys aged 11 or 12. HPV vaccines are administered as a 3-dose series with doses given at 0, 1-2, and 6 months. Bivalent, quadrivalent, and 9-valent HPV vaccine all protect against HPV 16 and 18, the HPV types that cause about 66% of cervical cancers and the majority of other HPV-attributable cancers in the United States.
The 9-valent HPV vaccine targets 5 additional cancer-causing types, which account for about 15% of cervical cancers. Quadrivalent and 9-valent HPV vaccine also protect against HPV 6 and 11, the HPV types that cause anogenital warts. The additional five types of HPV targets in 9-valent HPV vaccine account for a higher proportion of HPV-associated cancers in women compared with men. These HPV types can also cause cervical precancers in women. Therefore, the additional protection from 9-valent HPV vaccine will be of greater benefit to women.
It is believed that through utilization of the HPV vaccine we will see a significant decrease in the number of oropharyngeal carcinomas. Scientific research shows the benefits of HPV vaccination far outweigh the potential risks. More than 80 million doses of HPV vaccine have been distributed since the vaccine was introduced in 2006.1 The most common side effects associated with HPV vaccines are mild and may include pain, redness, or swelling in the arm where the vaccine was given.
HPV and CancerMost HPV types infect cutaneous epithelial cells and cause common warts, such as those that occur on the hands and feet. Approximately 40 HPV types infect mucosal epithelial cells on the genitals and the mouth and throat. Persistent infections with high-risk (oncogenic) HPV types can cause cancers of the anus, cervix, penis, vulva, and vagina, as well as the oropharynx (defined as the back of the throat, including the base of the tongue and tonsils). The most common high-risk types are 16 and 18. More research is needed to understand all the factors leading to oropharyngeal cancers.
Patients with HPV-positive oropharyngeal cancer are approximately 10 years younger when compared with HPV-negative patients. Many of the patients seen with this disease are in their late 30s or early 40s. This difference in patient age has major implications in terms of performance status, comorbidities, and the ability to tolerate treatment, which can affect the prognosis.
HPV-associated tumors predominantly arise in the base of the tongue or the tonsillar region, although a small percentage of tumors at other sites are also HPV-positive. Why the oropharynx is more susceptible than other sites to HPV transmission is unclear. Similar to the cervix, the oropharynx offers easy access for infection. The tonsils contain deep invaginations of the mucosal surface believed to favor the capture and processing of antigens, which may facilitate viral access to basal cells.
Jennifer Cerar, RN, CRRN
StagingHPV-associated oropharyngeal cancer currently is staged using the same tumor, node, metastasis (TNM) staging system as for those with HPV-negative oropharyngeal cancers. However, given the differences in clinical presentation and the natural history of disease, the TNM staging system for HPV-positive disease is under review and may require modification.
Currently, regardless of whether the cancer was caused by HPV or smoking/alcohol, the treatment and perceived prognosis based on tumor staging has remained the same—even though patient outcomes vary considerably.7
For example, a stage IV patient with HPV-related cancer has an 80% survival rate, whereas a stage IV smoking-related cancer patient has a 50%-60% survival rate; both are presently considered advanced stage—which is recognized as a life-threatening prognosis. Studies such as the ECOG 2399)5 have reported improved outcomes for the HPV-associated cancers, adding evidence that a new tumor staging model would help to separate patients with promising prognoses from those with negative prognoses to design the most appropriate treatment strategies for each group.8
Dental Prophylaxis in Head and Neck CancerWhen the treatment for cancer of the head and neck requires radiation therapy, a thorough dental examination is required prior to radiation treatment. A dentist specializing in dental prophylaxis will complete a thorough screening, including radiographs to assess the health of the teeth and the jaw. Teeth in the field of the radiation should be extracted if gum depth is ≥5mm. Root canals in the field of radiation should be considered for extraction as well as impactions and large fillings or fractures. This screening can help patients avoid many complications and achieve optimal results.
During radiation treatment planning, it is very difficult to exclude the salivary glands from the radiation fields in the head and neck. Radiation therapy may affect the salivary glands, and the result is a change in the quantity and quality of the saliva. Saliva is important when discussing oral health, because it both lubricates the mouth and balances the mouth’s acidity, thereby preventing tooth decay. As a result of radiation, most patients experience dryness in the mouth, called xerostomia.
A certain amount of dryness will probably persist indefinitely after radiation therapy to the head and neck. The most common problem associated with dry mouth is rampant dental decay and periodontal disease. Another more serious effect of radiation is a decrease in the size and number of blood vessels in the area of radiation. This causes a decrease in the ability of irradiated tissue and bone to heal following surgery, injury, or infection, occasionally resulting in osteoradionecrosis.
Radiation Side EffectsRadiation therapy may cause some reactions or side effects. Acute side effects may include fatigue, skin irritation, sore throat/mouth, thick oral mucous, and loss of taste, change in appetite, temporary loss of facial hair, mucositis, and nausea /vomiting. Late side effects may include, fatigue, dry mouth, chronic swelling of throat, poor wound healing after trauma, dental extraction, difficulty swallowing, poor taste, trismus, loss of thyroid function, and fibrosis.
Head and neck cancer therapy remains a difficult challenge for most patients and is exacerbated by the toxicity associated with current treatments. Although most delayed side effects in the treatment of head and neck malignancies occur within the first 3 years after initiation of treatment, some may appear or progress much later, emphasizing the need for long-term follow-up.
Gloria Wood, BSN, RN, and Jennifer Cerar, RN, CRRN, are nursing specialists in the Radiation Oncology Program at Moffitt Cancer Center, Tampa, Florida.
- Centers for Disease Control and Prevention. Human Papillomavirus. http://www.cdc.gov/std/hpv/.
- Gillison ML, Broutian T, Pickard RK, Prevalence of oral HPV infection in the United States, 2009–2010. JAMA. 2012; 307(7):693-703.
- 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.
- Fakhry C, Westra WH, Li S, et al. Improved survival of patients with human papillomavirus-positive head and neck squamous cell carcinoma in a prospective clinical trial. J Natl Cancer Inst. 2008;100(4):261-269.
- Chaturvedi AK, Anderson WF, Lortet-Tieulent J, et al. Worldwide trends in incidence rates for oral cavity and oropharyngeal cancers. J Clin Oncol. 2013;31(36):4550-4559.
- Walline HM, Komarck C, McHugh JB, et al. High-risk human papillomavirus detection in oropharyngeal, nasopharyngeal, and oral cavity cancers. JAMA Otolaryngol Head Neck Surg. 2013;139(12):1320-1327.
- Lewis J, Thorstad W, Chernock R, et al. (2010). p16 positive oropharyngeal squamous cell carcinoma: an enitity with a favorable prognosis regardless of tumor HPV status. Am J Surg Pathol. 2010;34(8): 1088-1096
- Huang S, Xu W, Waldron J, et al. (2015). Refining american joint committee on cancer/union for intentional cancer control tnm stage and prognostic groups for human papillomavirus-related oropharyngeal carcinomas. J Clin Oncol. 2015;33(8):836-845.
- D’Souza G, Kreimer AR, Viscidi R, et al. Case-control study of human papillomavirus and oropharyngeal cancer. New Engl J. Med. 2007;356(19):1944-1956.