Prevalence of mucosal and cutaneous human papillomaviruses in different histologic subtypes of vulvar carcinoma

Mod Pathol. 2008 Mar;21(3):334-44. doi: 10.1038/modpathol.3801009. Epub 2008 Jan 11.


Two independent pathways of vulvar carcinogenesis have currently been identified, one related to infection with mucosal human papillomaviruses (HPVs) and a second related to chronic inflammatory or autoimmune processes. The goal of the study was to examine a possible role of cutaneous HPVs from the beta genus in vulvar carcinogenesis and to evaluate the distribution of intratypic variants of HPV 16 in HPV 16-positive vulvar cancer. Consecutive cases of vulvar carcinoma were retrieved from the files and included the following histologic subtypes: keratinizing (n=21), basaloid (n=7), warty (n=1), mixed basaloid-warty (n=4), verrucous (n=4), keratoacanthoma (n=1), basal cell carcinoma (n=1). All tumors were microdissected and tested for 25 beta HPV types and 25 mucosal HPV types. Cases identified as positive for HPV 16 were further tested for intratypic variants. All cases were immunostained for p16INK4a. Beta HPVs were not detected in any of the tumor cases. Mucosal HPVs were detected in all but one basaloid/warty carcinomas; of these, nine cases (82%) were positive for HPV 16, including five European subtypes, one African subtype, one North American subtype and two indeterminate subtypes. Two of four verrucous carcinomas were positive for HPV 6. Mucosal HPVs were not detected in keratinizing carcinomas, keratoacanthoma and basal cell carcinoma. All cases of basaloid/warty carcinomas, but none of the remaining tumors, overexpressed p16INK4a protein. Our data do not support a role of beta HPVs in the pathogenesis of vulvar carcinoma. The study reaffirms the role of mucosal HPVs, in particular that of HPV 16, in the pathogenesis of basaloid and warty tumor subtypes. The HPV 16 intratypic variation showed correlation with patients' ethnic background. P16INK4a immunostaining seems to be a sensitive and specific marker of vulvar carcinomas positive for oncogenic mucosal HPVs.

MeSH terms

  • Carcinoma, Squamous Cell / metabolism
  • Carcinoma, Squamous Cell / pathology
  • Carcinoma, Squamous Cell / virology*
  • Carcinoma, Verrucous / metabolism
  • Carcinoma, Verrucous / pathology
  • Carcinoma, Verrucous / virology*
  • Cyclin-Dependent Kinase Inhibitor p16 / analysis
  • DNA, Viral / analysis
  • Female
  • Human papillomavirus 16 / genetics
  • Human papillomavirus 16 / isolation & purification*
  • Humans
  • Mucous Membrane / pathology
  • Mucous Membrane / virology
  • Oncogene Proteins, Viral / metabolism
  • Organ Specificity
  • Papillomaviridae / genetics
  • Papillomaviridae / isolation & purification*
  • Papillomavirus E7 Proteins
  • Papillomavirus Infections / metabolism
  • Papillomavirus Infections / pathology
  • Papillomavirus Infections / virology
  • Repressor Proteins / metabolism
  • Skin / pathology
  • Skin / virology
  • Tumor Virus Infections / metabolism
  • Tumor Virus Infections / pathology
  • Tumor Virus Infections / virology
  • Vulvar Neoplasms / metabolism
  • Vulvar Neoplasms / pathology
  • Vulvar Neoplasms / virology*


  • Cyclin-Dependent Kinase Inhibitor p16
  • DNA, Viral
  • E6 protein, Human papillomavirus type 16
  • Oncogene Proteins, Viral
  • Papillomavirus E7 Proteins
  • Repressor Proteins
  • oncogene protein E7, Human papillomavirus type 16