title: Human papillomavirus DNA prevalence and type distribution in anal carcinomas worldwide.
abstract: Knowledge about human papillomaviruses (HPV) types involved in anal cancers in some world regions is scanty. Here, we describe the HPV DNA prevalence and type distribution in a series of invasive anal cancers and anal intraepithelial neoplasias (AIN) grades 2/3 from 24 countries. We analyzed 43 AIN 2/3 cases and 496 anal cancers diagnosed from 1986 to 2011. After histopathological evaluation of formalin-fixed paraffin-embedded samples, HPV DNA detection and genotyping was performed using SPF-10/DEIA/LiPA25 system (version 1). A subset of 116 cancers was further tested for p16(INK4a) expression, a cellular surrogate marker for HPV-associated transformation. Prevalence ratios were estimated using multivariate Poisson regression with robust variance in the anal cancer data set. HPV DNA was detected in 88.3% of anal cancers (95% confidence interval [CI]: 85.1-91.0%) and in 95.3% of AIN 2/3 (95% CI: 84.2-99.4%). Among cancers, the highest prevalence was observed in warty-basaloid subtype of squamous cell carcinomas, in younger patients and in North American geographical region. There were no statistically significant differences in prevalence by gender. HPV16 was the most frequent HPV type detected in both cancers (80.7%) and AIN 2/3 lesions (75.4%). HPV18 was the second most common type in invasive cancers (3.6%). p16(INK4a) overexpression was found in 95% of HPV DNA-positive anal cancers. In view of the results of HPV DNA and high proportion of p16(INK4a) overexpression, infection by HPV is most likely to be a necessary cause for anal cancers in both men and women. The large contribution of HPV16 reinforces the potential impact of HPV vaccines in the prevention of these lesions.
authors.affiliation: Unit of Infections and Cancer, Cancer Epidemiology Research Program, Institut Català d'Oncologia, Barcelona, Spain; CIBER en Epidemiología y Salud Pública (CIBERESP), Spain.
authors.forename: Laia
authors.initials: L
authors.lastname: Alemany
authors.forename: Maëlle
authors.initials: M
authors.lastname: Saunier
authors.forename: Isabel
authors.initials: I
authors.lastname: Alvarado-Cabrero
authors.forename: Beatriz
authors.initials: B
authors.lastname: Quirós
authors.forename: Jorge
authors.initials: J
authors.lastname: Salmeron
authors.forename: Hai-Rim
authors.initials: HR
authors.lastname: Shin
authors.forename: Edyta C
authors.initials: EC
authors.lastname: Pirog
authors.forename: Núria
authors.initials: N
authors.lastname: Guimerà
authors.forename: Gustavo
authors.initials: G
authors.lastname: Hernandez-Suarez
authors.forename: Ana
authors.initials: A
authors.lastname: Felix
authors.forename: Omar
authors.initials: O
authors.lastname: Clavero
authors.forename: Belen
authors.initials: B
authors.lastname: Lloveras
authors.forename: Elena
authors.initials: E
authors.lastname: Kasamatsu
authors.forename: Marc T
authors.initials: MT
authors.lastname: Goodman
authors.forename: Brenda Y
authors.initials: BY
authors.lastname: Hernandez
authors.forename: Jan
authors.initials: J
authors.lastname: Laco
authors.forename: Leopoldo
authors.initials: L
authors.lastname: Tinoco
authors.forename: Daan T
authors.initials: DT
authors.lastname: Geraets
authors.forename: Charles F
authors.initials: CF
authors.lastname: Lynch
authors.forename: Vaclav
authors.initials: V
authors.lastname: Mandys
authors.forename: Mario
authors.initials: M
authors.lastname: Poljak
authors.forename: Robert
authors.initials: R
authors.lastname: Jach
authors.forename: Josep
authors.initials: J
authors.lastname: Verge
authors.forename: Christine
authors.initials: C
authors.lastname: Clavel
authors.forename: Cathy
authors.initials: C
authors.lastname: Ndiaye
authors.forename: JoEllen
authors.initials: J
authors.lastname: Klaustermeier
authors.forename: Antonio
authors.initials: A
authors.lastname: Cubilla
authors.forename: Xavier
authors.initials: X
authors.lastname: Castellsagué
authors.forename: Ignacio G
authors.initials: IG
authors.lastname: Bravo
authors.forename: Michael
authors.initials: M
authors.lastname: Pawlita
authors.forename: William G
authors.initials: WG
authors.lastname: Quint
authors.forename: Nubia
authors.initials: N
authors.lastname: Muñoz
authors.forename: Francesc X
authors.initials: FX
authors.lastname: Bosch
authors.forename: Silvia
authors.initials: S
authors.lastname: de Sanjosé
mesh_terms: D000368:Aged; D001005:Anus Neoplasms / Q000453:epidemiology / Q000378:metabolism / Q000821:virology*; D002294:Carcinoma, Squamous Cell / Q000453:epidemiology / Q000378:metabolism / Q000821:virology*; D003430:Cross-Sectional Studies; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000378:metabolism; D004279:DNA, Viral / Q000235:genetics*; D005260:Female; D052162:Human papillomavirus 16 / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D030361:Papillomavirus Infections / Q000453:epidemiology / Q000378:metabolism / Q000821:virology*; D016012:Poisson Distribution; D015995:Prevalence; D012189:Retrospective Studies
chemical_list: D019941:Cyclin-Dependent Kinase Inhibitor p16; D004279:DNA, Viral
keywords: anal cancer; human papillomavirus; vaccine