title: Large contribution of human papillomavirus in vaginal neoplastic lesions: a worldwide study in 597 samples.
abstract: OBJECTIVE
  This work describes the human papillomavirus (HPV) prevalence and the HPV type distribution in a large series of vaginal intraepithelial neoplasia (VAIN) grades 2/3 and vaginal cancer worldwide.
  
  
  METHODS
  We analysed 189 VAIN 2/3 and 408 invasive vaginal cancer cases collected from 31 countries from 1986 to 2011. After histopathological evaluation of sectioned formalin-fixed paraffin-embedded samples, HPV DNA detection and typing was performed using the SPF-10/DNA enzyme immunoassay (DEIA)/LiPA25 system (version 1). A subset of 146 vaginal cancers was tested for p16(INK4a) expression, a cellular surrogate marker for HPV transformation. Prevalence ratios were estimated using multivariate Poisson regression with robust variance.
  
  
  RESULTS
  HPV DNA was detected in 74% (95% confidence interval (CI): 70-78%) of invasive cancers and in 96% (95% CI: 92-98%) of VAIN 2/3. Among cancers, the highest detection rates were observed in warty-basaloid subtype of squamous cell carcinomas, and in younger ages. Concerning the type-specific distribution, HPV16 was the most frequently type detected in both precancerous and cancerous lesions (59%). p16(INK4a) overexpression was found in 87% of HPV DNA positive vaginal cancer cases.
  
  
  CONCLUSIONS
  HPV was identified in a large proportion of invasive vaginal cancers and in almost all VAIN 2/3. HPV16 was the most common type detected. A large impact in the reduction of the burden of vaginal neoplastic lesions is expected among vaccinated cohorts.
authors.affiliation: Unit of Infections and Cancer, Cancer Epidemiology Research Program, Catalan Institute of Oncology, IDIBELL, L'Hospitalet de Llobregat, Barcelona, Spain; CIBER en Epidemiología y Salud Pública (CIBERESP), Spain. Electronic address: lalemany@iconcologia.net.
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authors.affiliation: Unit of Infections and Cancer, Cancer Epidemiology Research Program, Catalan Institute of Oncology, IDIBELL, L'Hospitalet de Llobregat, Barcelona, Spain.
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authors.affiliation: Unit of Infections and Cancer, Cancer Epidemiology Research Program, Catalan Institute of Oncology, IDIBELL, L'Hospitalet de Llobregat, Barcelona, Spain.
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authors.affiliation: Unit of Infections and Cancer, Cancer Epidemiology Research Program, Catalan Institute of Oncology, IDIBELL, L'Hospitalet de Llobregat, Barcelona, Spain; Hospital General de L'Hospitalet, Barcelona, Spain.
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authors.affiliation: Department of Gynaecology and Obstetrics, Medical University of Vienna, Comprehensive Cancer Center, Vienna, Austria.
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authors.affiliation: Unit of Infections and Cancer, Cancer Epidemiology Research Program, Catalan Institute of Oncology, IDIBELL, L'Hospitalet de Llobregat, Barcelona, Spain; CIBER en Epidemiología y Salud Pública (CIBERESP), Spain.
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authors.affiliation: Unit of Infections and Cancer, Cancer Epidemiology Research Program, Catalan Institute of Oncology, IDIBELL, L'Hospitalet de Llobregat, Barcelona, Spain.
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authors.affiliation: Centro de Oncología Preventiva, Universidad de Chile, Santiago, Chile.
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authors.affiliation: Instituto Potosino de Investigación Científica y Tecnológica, AC (IPICYT), San Luis Potosí, Mexico.
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authors.affiliation: DDL Diagnostic Laboratory, Rijswijk, The Netherlands.
authors.forename: W
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authors.affiliation: Unit of Infections and Cancer, Cancer Epidemiology Research Program, Catalan Institute of Oncology, IDIBELL, L'Hospitalet de Llobregat, Barcelona, Spain.
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authors.lastname: Muñoz
authors.affiliation: Unit of Infections and Cancer, Cancer Epidemiology Research Program, Catalan Institute of Oncology, IDIBELL, L'Hospitalet de Llobregat, Barcelona, Spain; CIBER en Epidemiología y Salud Pública (CIBERESP), Spain.
authors.forename: S
authors.initials: S
authors.lastname: de Sanjosé
authors.affiliation: Unit of Infections and Cancer, Cancer Epidemiology Research Program, Catalan Institute of Oncology, IDIBELL, L'Hospitalet de Llobregat, Barcelona, Spain.
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mesh_terms: D000368:Aged; D002294:Carcinoma, Squamous Cell / Q000150:complications / Q000453:epidemiology / Q000821:virology*; D003430:Cross-Sectional Studies; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000378:metabolism; D004279:DNA, Viral / Q000032:analysis; D005260:Female; D052162:Human papillomavirus 16 / Q000302:isolation & purification; D006801:Humans; D007124:Immunoenzyme Techniques; D007391:International Cooperation; D008875:Middle Aged; D027383:Papillomaviridae / Q000302:isolation & purification*; D030361:Papillomavirus Infections / Q000150:complications / Q000453:epidemiology / Q000821:virology*; D016012:Poisson Distribution; D011230:Precancerous Conditions / Q000453:epidemiology / Q000821:virology; D015995:Prevalence; D012044:Regression Analysis; D012189:Retrospective Studies; D016896:Treatment Outcome; D014625:Vaginal Neoplasms / Q000150:complications / Q000453:epidemiology / Q000821:virology*
chemical_list: D019941:Cyclin-Dependent Kinase Inhibitor p16; D004279:DNA, Viral
keywords: Human papillomavirus; Vaccine; Vaginal cancer; Vaginal intraepithelial neoplasia