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Recommendations for the use of human papillomavirus vaccines

J Thomas Cox, MD
Joel M Palefsky, MD
Section Editor
Martin S Hirsch, MD
Deputy Editor
Allyson Bloom, MD


Human papillomavirus is a sexually transmitted pathogen that causes anogenital disease in males and females. Persistent viral infection with high-risk human papillomavirus (HPV) genotypes causes virtually all cancers of the cervix. The same HPV genotypes (or "types") that cause cancer of the cervix also cause most cases of anal cancer [1] and significant proportion of oropharyngeal cancer in men and women, a significant proportion of vulvar and vaginal cancer, and significant proportion of penile cancer. Three vaccines have been developed against HPV infection; one is a quadrivalent vaccine (Gardasil), one is 9-valent (Gardasil 9), and the other is a bivalent vaccine (Cervarix).

This topic will cover issues related to routine immunization recommendations, vaccination in special patient populations, and vaccine safety. The natural history, details on epidemiology, and immunology of HPV infection are discussed elsewhere. (See "Epidemiology of human papillomavirus infections" and "The life cycle, natural history, and immunology of human papillomaviruses".)


HPV-related disease in females

Cervical cancer and precursor lesions — Cervical cancer is the third most common female cancer worldwide, with an estimated incidence of 530,000 and 270,000 related deaths in 2012; the attributable fraction due to HPV infection was estimated to be 100 percent [2,3]. HPV types 16 and 18 cause approximately 70 percent of cervical cancers and 50 percent of precancerous cervical lesions (ie, cervical intraepithelial neoplasia grade 2 and grade 3 [CIN2/3]). HPV types 31, 33, 45, 52, and 58 are estimated to cause an additional 19 percent of invasive cervical cancers [4]. The estimated annual incidence in the United States of CIN among females who undergo cervical cancer screening is 0.4 percent for CIN 1 and 0.5 percent for CIN 2/3 [5]. (See "Invasive cervical cancer: Epidemiology, risk factors, clinical manifestations, and diagnosis" and "Cervical intraepithelial neoplasia: Terminology, incidence, pathogenesis, and prevention", section on 'Incidence'.)

Vulvar and vaginal cancer and precursor lesions — Vulvar and vaginal cancer are rare cancers globally, with an estimated incidence of 27,000 vulvar cancers and 13,000 vaginal cancers in 2008; the attributable fraction due to HPV infection has been estimated to be 43 percent for vulvar cancer and 70 percent for vaginal cancer [2]. Other data have suggested that only 29 percent of vulvar cancers are HPV positive whereas 87 percent of vulvar intraepithelial neoplasia (VIN) are HPV positive [6]. HPV 16 and HPV 18 cause approximately 60 percent of HPV-positive vaginal cancers and precancerous vaginal lesions; HPV 16 and HPV 18 cause approximately 35 to 77 percent of HPV-positive vulvar cancers and 75 to 80 percent of precancerous vulvar lesions [6,7]. (See "Vaginal cancer" and "Vulvar intraepithelial neoplasia".)

HPV-related disease in females and males

Anal cancer and precursor lesions — Anal cancer is a rare cancer globally, with an estimated incidence of 27,000 in 2008 [2]. The attributable fraction of cases due to HPV is approximately 88 percent [2,8]. HPV types 16 and 18 cause approximately 70 to 85 percent of anal cancers and precancerous anal lesions (ie, anal intraepithelial neoplasia grade 2 and grade 3 [AIN2/3]) [1,8,9]. Although it remains an uncommon cancer, the incidence of anal cancer is increasing in the United States and other countries [10-12]. In data from the Surveillance, Epidemiology and End Results program of the National Cancer Institute, the annual incidence among males and females between 1994 and 2000 was approximately 2 per 100,000 [10]. The annual incidence of anal cancer among men who have sex with men (MSM) was estimated to be as high as 37 per 100,000 prior to the HIV epidemic [13], and the incidence of anal cancer among HIV-positive MSM is estimated to be approximately twice that of HIV-negative MSM [14,15]. (See "Classification and epidemiology of anal cancer", section on 'Epidemiology and risk factors'.)


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