Worldwide human papillomavirus genotype attribution in over 2000 cases of intraepithelial and invasive lesions of the vulva.

Human papillomavirus (HPV) contribution in vulvar intraepithelial lesions (VIN) and invasive vulvar cancer (IVC) is not clearly established. This study provides novel data on HPV markers in a large series of VIN and IVC lesions. Histologically confirmed VIN and IVC from 39 countries were assembled at the Catalan Institute of Oncology (ICO). HPV-DNA detection was done by polymerase chain reaction using SPF-10 broad-spectrum primers and genotyping by reverse hybridisation line probe assay (LiPA25) (version 1). IVC cases were tested for p16(INK4a) by immunohistochemistry (CINtec histology kit, ROCHE). An IVC was considered HPV driven if both HPV-DNA and p16(INK4a) overexpression were observed simultaneously. Data analyses included algorithms allocating multiple infections to calculate type-specific contribution and logistic regression models to estimate adjusted prevalence (AP) and its 95% confidence intervals (CI). Of 2296 cases, 587 were VIN and 1709 IVC. HPV-DNA was detected in 86.7% and 28.6% of the cases respectively. Amongst IVC cases, 25.1% were both HPV-DNA and p16(INK4a) positive. IVC cases were largely keratinising squamous cell carcinoma (KSCC) (N=1234). Overall prevalence of HPV related IVC cases was highest in younger women for any histological subtype. SCC with warty or basaloid features (SCC_WB) (N=326) were more likely to be HPV and p16(INK4a) positive (AP=69.5%, CI=63.6-74.8) versus KSCC (AP=11.5%, CI=9.7-13.5). HPV 16 was the commonest type (72.5%) followed by HPV 33 (6.5%) and HPV 18 (4.6%). Enrichment from VIN to IVC was significantly high for HPV 45 (8.5-fold). Combined data from HPV-DNA and p16(INK4a) testing are likely to represent a closer estimate of the real fraction of IVC induced by HPV. Our results indicate that HPV contribution in invasive vulvar cancer has probably been overestimated. HPV 16 remains the major player worldwide.

de Sanjosé S ，Alemany L ，Ordi J ，Tous S ，Alejo M ，Bigby SM ，Joura EA ，Maldonado P ，Laco J ，Bravo IG ，Vidal A ，Guimerà N ，Cross P ，Wain GV ，Petry KU ，Mariani L ，Bergeron C ，Mandys V ，Sica AR ，Félix A ，Usubutun A ，Seoud M ，Hernández-Suárez G ，Nowakowski AM ，Wilson G ，Dalstein V ，Hampl M ，Kasamatsu ES ，Lombardi LE ，Tinoco L ，Alvarado-Cabrero I ，Perrotta M ，Bhatla N ，Agorastos T ，Lynch CF ，Goodman MT ，Shin HR ，Viarheichyk H ，Jach R ，Cruz MO ，Velasco J ，Molina C ，Bornstein J ，Ferrera A ，Domingo EJ ，Chou CY ，Banjo AF ，Castellsagué X ，Pawlita M ，Lloveras B ，Quint WG ，Muñoz N ，Bosch FX ，HPV VVAP study group ... -  《-》

Human papillomavirus infection and p16(INK4a) protein expression in vulvar intraepithelial neoplasia and invasive squamous cell carcinoma.

Rufforny I ，Wilkinson EJ ，Liu C ，Zhu H ，Buteral M ，Massoll NA ... -  《Journal of Lower Genital Tract Disease》

Prevalence of human papillomavirus types in invasive vulvar cancers and vulvar intraepithelial neoplasia 3 in the United States before vaccine introduction.

Gargano JW ，Wilkinson EJ ，Unger ER ，Steinau M ，Watson M ，Huang Y ，Copeland G ，Cozen W ，Goodman MT ，Hopenhayn C ，Lynch CF ，Hernandez BY ，Peters ES ，Saber MS ，Lyu CW ，Sands LA ，Saraiya M ... -  《-》

Differentiated Vulvar Intraepithelial Neoplasia-like and Lichen Sclerosus-like Lesions in HPV-associated Squamous Cell Carcinomas of the Vulva.

Rakislova N ，Alemany L ，Clavero O ，Del Pino M ，Saco A ，Quirós B ，Lloveras B ，Alejo M ，Halec G ，Quint W ，de Sanjosé S ，Ordi J ，VVAP study group ... -  《-》

Vulvar squamous cell carcinoma is a multifactorial disease following two separate and independent pathways.

van der Avoort IA ，Shirango H ，Hoevenaars BM ，Grefte JM ，de Hullu JA ，de Wilde PC ，Bulten J ，Melchers WJ ，Massuger LF ... -  《INTERNATIONAL JOURNAL OF GYNECOLOGICAL PATHOLOGY》