Human papillomavirus (HPV) is the most common sexually transmitted infection in the U.S.¹ Twenty million people are currently infected, and another 6.2 million new infections occur annually.¹ Men and women between the ages of 15 and 24 account for nearly 75% of new infections,¹ and half of sexually active men and women are exposed to HPV at some point.² HPV is clearly linked to cervical and anal cancers. Recently, a link to nongenital regions such as the head, neck and oral cavity has been identified.^1,3

HPV Background

More than 100 species of HPV have been identified, and 40 primarily infect the mucosal epithelium in the anogenital regions.^1-3 HPV is classified as high risk or low risk. Low-risk HPV infections, commonly HPV-6 and HPV-11, result in abnormal cell growth but are nononcogenic.^1,3 High-risk infections are oncogenic due to their ability to transform epithelial cells into cancer cells.^1,4

Several high-risk viruses have been isolated, with HPV-16 and HPV-18 the most prevalent. These two types account for 70% of anogenital cancers (vulva, vagina, penis, anus and cervix).¹ Recently, research has determined that 90% of HPV-positive squamous cell cancers of the head and neck are associated with HPV-16.^5,6

Transmission of HPV

HPV can replicate effectively and quickly and can infect multiple sites.^1-3 Transmission of the virus occurs through microscopic tears on surface epithelial tissue during skin-to-skin contact.^1,2,3,7 After the virus has been transmitted to the impaired surface epithelium, it penetrates the basement membrane layer, where it can proliferate or remain inactive. During both circumstances, it can be transmitted.^2,8

At least one case control study identified a strong association between oral cancer and oral-genital contact.⁵ The researchers could not rule out transmission through mouth-to-mouth contact or other means.⁵ Most HPV infections, including high-risk types, are asymptomatic and subclinical, with 90% clearing naturally within 2 years.¹ Patients infected with HPV are generally unaware of it and inadvertently transmit the virus to others.

Risk Factors

The link between HPV and cancers of the head and neck was first proposed in the 1980s.^5-7 Recent studies involving more patients have identified molecular evidence of HPV and proposed it as an independent risk factor.^5,7 Historically, the primary risk factors for head and neck cancers were tobacco and heavy alcohol use, poor oral hygiene, previous upper aerodigestive tract carcinoma, sunlight exposure, poor diet, male sex, and genetics.^6,9 With the new link to HPV, additional risk factors include a high number of lifetime oral sex or genital sex partners, a history of casual sex, early age at first sexual contact, and infrequent use of condoms.⁵

In case-control studies, patients who reported one to five lifetime sexual partners faced a twofold increase in HPV-related cancers, while patients who reported six or more lifetime partners increased their odds fivefold.⁶

Head and Neck Cancer

Cancers of the head and neck are the eighth most common category of cancer worldwide. Incidence varies among developed and underdeveloped countries.⁷ In the U.S., head and neck cancers are responsible for 3% of all cancers.¹⁰ Incidence among white men rose in the United States in 2000, at the same time tumor evidence of HPV surfaced.¹¹

The National Cancer Institute categorizes head and neck cancers to include carcinomas in the oral cavity, the paranasal sinuses, pharyngeal or laryngeal tissue, the nasal cavity and the salivary glands.¹¹ A systematic review concluded that the largest majority of HPV-positive head and neck cancers are isolated to the oropharyngeal region.¹² The more common sites include the base of the tongue and the tonsils, specifically the lingual and palatine areas.^6,10

From 1974 to 2004, the incidence of head and neck cancers unrelated to HPV decreased, a likely result of reduced tobacco use.¹³ The incidence of HPV-positive head and neck cancers increased during the same period.¹³ New cases are primarily in adults 40 and younger.⁹ The incidence is higher among men than women.⁷ Black men have a higher incidence than white men and a mortality rate that is nearly twice as high.^7,9

Screening Recommendations

In 2007, 2.5 of every 100,000 cases of oropharyngeal cancer in the United States resulted in death.¹⁴ In response to this, one goal of Healthy People 2020 is to reduce the oropharyngeal cancer death rate by 10%, with specific emphasis on detection in the earliest stage.¹⁴ Routine screening of patients at high risk could result in the early detection of potentially malignant or malignant lesions.¹⁵

The American Cancer Society supports routine cancer-related health examinations for patients 20 and older, encompassing health counseling and screening of multiple high-risk areas, including the oral cavity.¹⁶ The American Dental Association endorses the concept that all patients, and particularly those at risk, receive routine visual and tactile examinations to evaluate for oral lesions.¹⁵

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The 5-year survival rate for early detection of localized head and neck cancer is 83%, but this rate drops to 32% if metastasis occurs.¹⁶ Diagnosis at an early localized stage also results in less aggressive treatment and improved quality of life.^6,17

History and Physical

The foundation for a successful focused screening and physical examination begins with a health history and review of systems.¹⁸ Important points to include are tobacco and alcohol use, dietary patterns, ultraviolet light exposure, and sexual history.^9,15,17,18 A personal or family history of cancer, specifically of the upper aerodigestive tract, or a personal history of head and neck radiotherapy, should be reviewed in detail.^15,18 Common red flags should not be overlooked, regardless of risk factors (see table).

A head, neck and oral examination can be performed in the primary care setting. A bedside oral examination has a sensitivity ranging from 60% to 97%.⁹ The following primary supplies should be available: sufficient light source, mirrors (laryngeal or nasopharyngeal), gloves, tongue blades and 2-inch-by-2-inch gauze.¹⁸ All tissue and mucosal surfaces must be assessed for pigmentation or texture changes, ulcerations, masses or unexplained bleeding.^9,15,18,19 Common presentations of premalignant oral lesions include leukoplakia and erythroplakia.^17,18

Leukoplakia are white plaque lesions that do not rub off. Erythroplakia are red lesions that are flat, macular and velvety; they often include white speckles.¹⁸ Erythroplakia is less common than leukoplakia and has a greater probability of being malignant at detection.^17,18

Screening Tools

It is important to be aware of screening tools beyond visual inspection that can improve detection. These include the toluidine blue test, light visualization technology, brush cytology, flexible scope and salivary biomarkers.⁹ However, no data support the contention that these technologies can identify premalignant lesions before they can be picked up in a clinical bedside examination.⁹ Regardless of the screening tools used, all clinicians should coordinate prompt evaluation of suspicious lesions. The gold standard for evaluating concerning tissue or lesions is an incisional or excisional biopsy.^9,17,19

Prevention of HPV

Education about transmission, risk factors and preventive measures is essential. Abstinence from all sexual contact is the only prevention strategy that is 100% effective. A misconception is that the use of condoms can prevent transmission of HPV. The National Institutes of Health Condom Effectiveness Panel concluded that condoms are not an effective measure in the prevention of sexually transmitted infections other than HIV and gonorrhea.⁹

HPV Vaccination

The main risk factor for HPV-positive head and neck cancer is oral infection with HPV, specifically HPV-16.¹⁵ Insufficient research exists to support the use of HPV vaccinations for the

prevention of head and neck cancer. HPV vaccinations have been proven effective in the prevention of cervical cancer.^1,20

The Food and Drug Administration has approved two HPV vaccines.²¹ HPV4 (Gardasil) is a quadrivalent vaccine providing protection against HPV 6, 11, 16 and 18.^1,20 HPV2 (Cervarix) is a bivalent vaccine that provides protection against HPV 16 and 18.^1,21 The Advisory Committee on Immunization Practices recommends vaccination for the prevention of cervical cancer.²⁰ The HPV4 is recommended for girls aged 11 or 12. The series can be started as early as age 9, and follow-up vaccination can occur at ages 13 through 26.¹ The HPV2 vaccine can be used for girls ages 10 through 25.²⁰ For boys, the committee recommends vaccination at age 11 or 12.²² Young men ages 13 to 26 who have not initiated or completed the series should receive the vaccine.²²

References

1. Human Papillomavirus. In: Atkinson W, Wolfe S, Hamborsky J, eds. Epidemiology and Prevention of Vaccine-Preventable Diseases. 12th ed. Atlanta: Centers for Disease Control and Prevention; 2011:139-149.

2. Hager WD. Human papillomavirus infection and prevention in the adolescent population. J Pediatr Adolesc Gyn. 2009;22(4):197-204.

3. National Cancer Institute. HPV and cancer. http://www.cancer.gov/cancertopics/factsheet/Risk/HPV

4. Mannarini L, et al. Human papilloma virus (HPV) in head and neck region: review of literature. Acta Otorhinolaryngol Ital. 2009;29(3):119-126.

5. D'Souza G, et al. Case-control study of human papillomavirus and oropharyngeal cancer. N Engl J Med. 2007;356(19):1944-1956.

6. Marur S, et al. HPV-associated head and neck cancer: a virus-related cancer epidemic. Lancet Oncol. 2010;11(8):781-789.

7. Ragin CC, et al. The epidemiology and risk factors of head and neck cancer: a focus on human papillomavirus. J Dent Res. 2007;86(2):104-114.

8. Einstein MH, et al. Clinician's guide to human papillomavirus immunology: knowns and unknowns. Lancet Infect Dis. 2009;9(6):347-56.

9. Eusterman VD. History and physical examination, screening and diagnostic testing. Otolaryngol Clin North Am. 2011;44(1):1-29.

10. National Cancer Institute. Head and neck cancers. http://www.cancer.gov/cancertopics/factsheet/Sites-Types/head-and-neck

11. Simard E, et al. Cancer with increasing trends in United States, 1999-2008. Cancer. 2012;62(2):118-128.

12. Kreimer AR, et al. Human papillomavirus types in head and neck squamous cell carcinomas worldwide: a systematic review. Cancer Epidemiol Biomarkers Prev. 2005;14(2):467-475.

13. Chaturvedi AK, et al. Incidence trends for human papillomavirus-related and -unrelated oral squamous cell carcinomas in the United States. J Clin Oncol. 2008;26(4):612-619.

14. U.S. Department of Health and Human Services. Cancer. Healthy People 2020. Washington, D.C.: NIH; 2010: 29.

15. Rethman MP, et al. Evidence-based clinical recommendations regarding screening for oral squamous cell carcinomas. J Am Dent Assoc. 2010;141(5):509-520.

16. American Cancer Society. Oral cavity and oropharyngeal cancer. http://www.cancer.org/Cancer/OralCavityandOropharyngealCancer/DetailedGuide/index

17. National Institute of Dental and Craniofacial Research. Detecting oral cancer: a guide for health care professionals. http://www.nidcr.nih.gov/OralHealth/Topics/OralCancer/DetectingOralCancer.htm

18. Barker G et al. The CDC oral cancer background papers. (Chapters I-IX) http://oralcancerfoundation.org/cdc/index.htm

19. Crozier E, Sumer BD. Head and neck cancer. Med Clin N Am. 2010;94(5):1031-1046.

20. Centers for Disease Control and Prevention. FDA licensure of bivalent human papillomavirus vaccine (HPV2, Cervarix) for use in females and updated HPV vaccination recommendations from the ACIP. MMWR. 2010;59(20):626-629.

21. FDA licensure of quadrivalent human papillomavirus vaccine (HPV4, Gardasil) for use in males and guidance from the Advisory Committee on Immunization Practices. MMWR. 2010;59(20):630-632.

22. Centers for Disease Control and Prevention. Recommendations on the use of quadrivalent human papillomavirus vaccine in males. MMWR. 2011;60(50):1705-1708.

Christina Gisvold is a family nurse practitioner in the interventional radiology department at St. Alexius Medical Center in Bismarck, N.D. She has completed a disclosure statement and reports no relationships related to this article.