Prevalence and type distribution of human papillomavirus in carcinoma and intraepithelial neoplasia of the vulva, vagina and anus: A meta‐analysis

Abstract

This meta-analysis investigated human papillomavirus (HPV) prevalence in vulvar, vaginal and anal intraepithelial neoplasia (VIN, VAIN, AIN) grades 1-3 and carcinoma from 93 studies conducted in 4 continents and using PCR assays. Overall HPV prevalence was 67.8%, 85.3% and 40.4% among 90 VIN1, 1,061 VIN2/3 and 1,873 vulvar carcinomas; 100%, 90.1% and 69.9% among 107 VAIN1, 191 VAIN2/3 and 136 vaginal carcinomas; and 91.5%, 93.9% and 84.3% among 671 AIN1, 609 AIN2/3 and 955 anal carcinomas, respectively. HPV16 was found more frequently (>75%) and HPV18 less frequently (<10%) in HPV-positive vulvar, vaginal and anal carcinomas than in cervical carcinoma. HPV6 and 11 were common in VIN1 and AIN1, but not in VAIN1. HPV prevalence in vulvar carcinoma varied most by histological type (69.4% in warty-basaloid and 13.2% in keratinized type) and was also higher in women 60 years or younger and in studies carried out in North America. HPV prevalence in anal carcinoma was higher among women (90.8%) than men (74.9%), but no difference by gender emerged in North America. The majority of AIN2/3 derived from studies of HIV-positive individuals and/or men who have sex with men. Among AIN2/3, HIV infection was associated with higher HPV prevalence, more multiple-type infections and a relative under-representation of HPV16. In conclusion, 40% of vulvar, 60% of vaginal and 80% of anal carcinoma may be avoided by prophylactic vaccines against HPV16/18. This proportion would be similar for the corresponding high-grade lesions of the vagina and anus, but higher for VIN2/3 (75%) than for vulvar carcinoma. ' 2008 Wiley-Liss, Inc.Key words: vulva; vagina; anus; carcinoma; human papillomavirus; human immunodeficiency virus; meta-analysis Anogenital carcinomas other than cervical carcinoma are relatively rare. Only a few areas of the United States show age-standardized incidence rates for vulvar carcinoma in women, or anal carcinoma in men, greater than 2 per 100,000, and those for vaginal cancer in all parts of the world are below 1 per 100,000.1 Anogenital carcinomas share many risk factors with cervical carcinoma, namely those relating to sexual behavior and smoking, [2][3][4][5][6] and immunosuppression. 7,8 Increases in their incidence have been reported in the last decades in some high-resource countries, notably in women and men below age 50 years. [9][10][11][12][13] In 2005, an expert working group convened by the International Agency for Research on Cancer established a causal role for human papillomavirus (HPV) 16 in a subset of vulvar, vaginal and anal carcinoma.14 A similar role for types other than HPV16 could not be established due to the limited number and size of the reviewed studies.Also strongly related to HPV are vulvar, vaginal and anal intraepithelial neoplasia (VIN, VAIN, AIN) grades 1-3, which are considered precursor lesions of carcinoma in the corresponding sites. However, scant data are available on the HPV types that contribute to intraepithelial neoplasia, as well as their potential to progress to carcinoma i...

Human papillomavirus in vaginal intraepithelial neoplasia

“…The most common HPV types in VAIN2/3 were HPV16 (57.6%), 18 (6.9%) and 58 (5.9%). 9 Our results indicate that the leading HPV types were HPV16 (35.5%), HPV58 (9.9%), HPV52 (9.9%), HPV39 (8.4%), HPV33 (7.3%) and HPV53 (7.0%). Notably, HPV18 was rare (2.7%) in VAIN samples in our study.…”

“…3,4 The review by Smith et al 8 found HPV positivity in 98.5% of VAIN1 samples and in 92.6% of VAIN2/3 samples. De Vuyst et al 9 reported HPV positivity in 100% of VAIN1 samples and in 90.1% of VAIN2/3 samples.…”

“…In VAIN2/3 (n ¼ 191), the most common HPV types were HPV16 (57.6%), HPV 18 (6.9%) and HPV 58 (5.9%). 9 With the advent of HPV vaccines, cervical neoplasms of the HPV types included in the vaccine are not the only types of neoplasms that are prevented 16 ; the incidences of VAIN and vulvar intraepithelial neoplasia are also significantly reduced. 17 Using SEER data (1992-2004, Balamurugan et al 18 found that there was a significantly elevated risk for subsequent in situ cancers of the vagina and vulva (standardized incidence ratios [SIRs] of 53.8 and 6.6, respectively) and invasive vaginal and vulvar cancers (SIRs of 29.9, and 5.7, respectively) among cervical cancer survivors.…”

“…1,[4][5][6][7] Previous studies regarding HPV types in VAIN and vaginal cancer or comparisons of HPV types between incident vaginal and previous cervical lesions were limited by small sample sizes and inconsistent conclusions. 3,4,[8][9][10][11][12][13][14][15] Smith et al 8 published a systemic review of 725 abstracts, in which the HPV detection rates among 166 cases of VAIN2/3 and 66 cases of VAIN1 were 92.6% and 98.5%, respectively. Another systemic review of 22 U.S. studies found HPV16/18 to be the predominant type in VAIN3 (n ¼ 97, 65.1%).…”

“…Another systemic review of 22 U.S. studies found HPV16/18 to be the predominant type in VAIN3 (n ¼ 97, 65.1%). 10 A meta-analysis of 93 studies 9 including 298 cases of VAIN from four continents noted that HPV testing was positive in 100% of VAIN1 and 90.1% of VAIN2/3. In VAIN2/3 (n ¼ 191), the most common HPV types were HPV16 (57.6%), HPV 18 (6.9%) and HPV 58 (5.9%).…”