Abstract & Commentary
A New Indication for HPV Vaccination Prevention of Anal Cancer
By Stan Deresinski, MD, FACP, FIDSA, Clinical Professor of Medicine, Stanford, Associate Chief of Infectious Diseases, Santa Clara Valley Medical Center, is Editor for Infectious Disease Alert.
GARDASIL® (Human Papillomavirus Quadrivalent [Types 6, 11, 16, 18] Vaccine, Recombinant) previously received FDA approval for prevention of cervical, vulvar, and vaginal cancer and associated precancerous lesions, and for prevention of genital warts in males and females 9-26 years of age. More recently, it failed to receive approval for these indications in women 27-45 years of age because of lack of demonstrated efficacy.1 At the end of 2010, FDA approved the use of this viral-like particle vaccine for the prevention of anal cancer and associated precancerous lesions due to human papillomavirus (HPV) types 6, 11, 16, and 18 in people (all genders) ages 9-26 years.2,3
It is estimated that approximately 5,300 individuals receive a diagnosis of anal cancer each year in the United States. While the total number affected is relatively low, effective treatment of this potentially life-threatening malignancy is difficult. Most anal malignancies are squamous cell cancers in which infection with oncogenic types of HPV, especially types 16 and 18, play an etiologic role.
While a majority of anal carcinomas occur in women, men who have sex with men (MSM) have the highest incidence and, as a result, comprised the study population in a randomized placebo-controlled trial in which they were a subset. The full trial, which enrolled a total of 4,055 males, 16-26 years of age, demonstrated the efficacy of the vaccine in the prevention of anogenital warts and precancerous lesions. Among these were 299 MSM who received placebo and 299 who received GARDASIL who were followed for a median duration of 2.3 years. Cases of anal intraepithelial neoplasia grades 1/2/3 and anal cancer made up the composite efficacy endpoint used to assess prevention of HPV-related anal cancer.
GARDASIL had a 77.5% efficacy in prevention of the composite endpoint caused by HPV types included in the vaccine in a per-protocol analysis of subjects who were naïve (by PCR and antibody) to these viruses at baseline. This finding led the FDA to approve the use of this vaccine for the prophylaxis of anal cancer and precancerous lesions. Because anal cancer is the same disease in both males and females, the approval was extended to females in the same age group.
This information strengthens the indication for vaccination of young females and indicates the desirability of targeting young MSM for vaccination as well. Among HIV-infected MSM, the Multicenter AIDS Cohort Study (MACS) reported an overall incidence rate of anal cancer of 69 per 100,000 person-years.4 Furthermore, the incidence of anal cancer in this group has been increasing in the United States despite the introduction of effective antiretroviral therapy from 19.0 per 100,000 person-years in 1992-1995 to 48.3 in 1996-1999 (shortly after the introduction of potent combination antiretroviral therapy) to 78.2 per 100,000 person-years in 2000-2003.5
Condom use may reduce HPV transmission. Another important element in the prevention of anal cancer could be implementation of screening. There is, however, a lack of general acceptance of routine screening analogous to that used for prevention of cervical cancer. The most recent USPHS guideline states that, until the issue is settled by definitive evidence, "some experts recommend an annual digital rectal examination as an important procedure to detect masses on palpation that may be anal cancer (BIII). There are no national recommendations for routine screening for anal cancer. However, some specialists currently recommend anal cytologic screening for HIV-seropositive men and women (CIII). If anal cytology is performed and indicates ASC-US or ASC-H, LSIL, or HSIL (BIII), then it should be followed by high-resolution anoscopy (HRA). Visible lesions should be biopsied to determine the level of histologic changes and to rule out invasive cancer (BIII)."
- Clinical Review of Biologics License Application Supplement STN# 125126/773 mid-adult women indication for GARDASIL. Available at: www.fda.gov/downloads/BiologicsBloodVaccines/Vaccines/ApprovedProducts/UCM251763.pdf.
- Clinical Review of Biologics License Application Supplement STN# 125126/1297.0 male indication for GARDASIL. Available at: www.fda.gov/downloads/BiologicsBloodVaccines/Vaccines/ApprovedProducts/UCM190977.pdf.
- GARDASIL [Human Papillomavirus Quadrivalent (Types 6, 11, 16, and 18) Vaccine, Recombinant] Suspension for intramuscular injection. Available at: www.fda.gov/downloads/biologicsbloodvaccines/vaccines/approvedproducts/ucm111263.pdf.
- Heard I. Human papillomavirus, cancer and vaccination. Curr Opin HIV AIDS 2011 Apr 23; Epub ahead of print.
- Kaplan JE, Benson C, Holmes KH, et al; Centers for Disease Control and Prevention (CDC); National Institutes of Health; HIV Medicine Association of the Infectious Diseases Society of America. Guidelines for prevention and treatment of opportunistic infections in HIV-infected adults and adolescents: Recommendations from CDC, the National Institutes of Health, and the HIV Medicine Association of the Infectious Diseases Society of America. MMWR Recomm Rep 2009;58(RR-4):1-207.