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Prevalence of Human Papillomavirus Types in Invasive Vulvar Cancers and Vulvar Intraepithelial Neoplasia 3 in the United States Before Vaccine Introduction

Gargano, Julia W. PhD1,2; Wilkinson, Edward J. MD3; Unger, Elizabeth R. PhD, MD2; Steinau, Martin PhD2; Watson, Meg MPH4; Huang, Youjie DrPH, MD5; Copeland, Glenn MBA6; Cozen, Wendy DO, MPH7; Goodman, Marc T. PhD, MPH8; Hopenhayn, Claudia PhD, MPH9; Lynch, Charles F. PhD, MD10; Hernandez, Brenda Y. PhD8; Peters, Edward S. ScD, DMD11; Saber, Maria Sibug MD7; Lyu, Christopher W. MPA12; Sands, Lauren A. BA2; Saraiya, Mona MD, MPH5

Journal of Lower Genital Tract Disease: October 2012 - Volume 16 - Issue 4 - p 471–479
doi: 10.1097/LGT.0b013e3182472947
Basic Science

Objective The study aimed to determine the baseline prevalence of human papillomavirus (HPV) types in invasive vulvar cancer (IVC) and vulvar intraepithelial neoplasia 3 (VIN 3) cases using data from 7 US cancer registries.

Materials and Methods Registries identified eligible cases diagnosed in 1994 to 2005 and requested pathology laboratories to prepare 1 representative block for HPV testing on those selected. Hematoxylin-eosin–stained sections preceding and following those used for extraction were reviewed to confirm representation. Human papillomavirus was detected using L1 consensus polymerase chain reaction (PCR) with PGMY9/11 primers and type-specific hybridization, with retesting of samples with negative and inadequate results with SPF10 primers. For IVC, the confirmatory hematoxylin-eosin slides were re-evaluated to determine histological type. Descriptive analyses were performed to examine distributions of HPV by histology and other factors.

Results Human papillomavirus was detected in 121/176 (68.8%) cases of IVC and 66/68 (97.1%) cases of VIN 3 (p < .0001). Patients with IVC and VIN 3 differed by median age (70 vs 55 y, p = .003). Human papillomavirus 16 was present in 48.6% of IVC cases and 80.9% of VIN 3 cases; other high-risk HPV was present in 19.2% of IVC cases and 13.2% of VIN 3 cases. Prevalence of HPV differed by squamous cell carcinoma histological subtype (p < .0001) as follows: keratinizing, 49.1% (n = 55); nonkeratinizing, 85.7% (n = 14), basaloid, 92.3% (n = 14), warty 78.2% (n = 55), and mixed warty/basaloid, 100% (n = 7).

Conclusions Nearly all cases of VIN 3 and two thirds of IVC cases were positive for high-risk HPV. Prevalence of HPV ranged from 49.1% to 100% across squamous cell carcinoma histological subtypes. Given the high prevalence of HPV in IVC and VIN 3 cases, prophylactic vaccines have the potential to decrease the incidence of vulvar neoplasia.

Nearly all cases of vulvar intraepithelial neoplasia 3 and two thirds of invasive vulvar cancer cases were human papillomavirus positive; human papillomavirus prevalence was 49% to 100% across vulvar squamous cell carcinoma subtypes.

1Epidemic Intelligence Service; 2Division of High-Consequence Pathogens and Pathology, National Center for Emerging and Zoonotic Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, GA; 3Department of Pathology, Immunology, and Laboratory Medicine, College of Medicine, University of Florida, Gainesville, FL; 4Division of Cancer Prevention and Control, National Center for Chronic Disease Prevention and Health Promotion, Centers for Disease Control and Prevention, Atlanta, GA; 5Bureau of Epidemiology, Florida Department of Health, Tallahassee, FL; 6Michigan Department of Community Health, Lansing, MI; 7Norris Comprehensive Cancer Center and Department of Pathology, Keck School of Medicine, University of Southern California, Los Angeles, CA; 8University of Hawaii Cancer Center, University of Hawaii, Honolulu, HI; 9Department of Epidemiology, College of Public Health and Markey Cancer Control Program, University of Kentucky, Lexington, KY; 10Department of Epidemiology, College of Public Health, The University of Iowa, Iowa City, IA; 11Department of Epidemiology, School of Public Health, Louisiana State University Health Sciences Center, New Orleans, LA; and 12Battelle Memorial Institute, Durham, NC

Correspondence to: Julia W. Gargano, PhD, MS C09, 1600 Clifton Road, NE, Centers for Disease Control and Prevention, Atlanta, GA 30333. E-mail:

The support for the collection of original specimens from nonrepositories (Kentucky, Florida, Michigan, and Lousiana), the coordination of genotyping data from both registries of Surveillance Epidemiology and End Results and National Program of Cancer Registries, and the genotyping was largely supported by Centers for Disease Control and Prevention intramural funds and Vaccine for Children funds. This project has been supported in part with federal funds by the Centers for Disease Control and Prevention under grant number no. 5U58DP000810-5 (Kentucky), 5U58DP000844-5 (Florida), 5U58DP000812-5 (Michigan), and 5U58DP000769-5 (Louisiana) and with federal funds for residual tissue repositories from the National Cancer Institute Surveillance Epidemiology and End Results population–based registry program, National Institutes of Health, Department of Health and Human Services, under contract no. N01-PC-35139 (Los Angeles), N01-PC-35143 (Iowa), and N01-PC-35137 (Hawaii).

The collection of data from California used in this publication was largely supported by the California Department of Health Services as part of the statewide cancer reporting program mandated by California Health and Safety Code Section 103885; by the National Cancer Institute, National Institutes of Health, Department of Health and Human Services under contract no. N01-PC-2010-00035; and by grant number 1U58DP000807-3 from the Centers for Disease Control and Prevention.

The findings and conclusions in this article are those of the author(s) and do not necessarily represent the official position of the Centers for Disease Control and Prevention.

©2012The American Society for Colposcopy and Cervical Pathology