Human papillomavirus as a favorable prognostic biomarker in squamous cell carcinomas of the vagina

Gynecol Oncol. 2012 Apr;125(1):194-9. doi: 10.1016/j.ygyno.2011.12.449. Epub 2012 Jan 4.


Objective: Recent evidence has confirmed two independent pathways in the development of vaginal squamous cell carcinoma (VaSCC): one related to and the other independent of human papillomavirus (HPV). The aim of our study was to evaluate whether HPV status has prognostic significance in this neoplasm.

Methods: All confirmed primary VaSCCs diagnosed and treated from 1995 to 2009 in two institutions were retrospectively evaluated (n=57). HPV infection was detected by PCR using SPF-10 primers and typed with the INNO-LIPA HPV assay and p16(INK4a) expression by immunohistochemistry. Disease-free and overall survival (DFS and OS) were analyzed by Kaplan-Meier analysis with the log-rank test and a multivariate Cox proportional hazard's model.

Results: HR-HPV DNA was detected in 70.2% patients. HPV16 was the most prevalent genotype (67.5% of cases). p16(INK4a) was positive in 97.5% HPV-positive and 17.6% HPV-negative tumors (p<.001). FIGO stage was associated with DFS (p=.042) and OS (p=.008). HPV-positive tumors showed better DFS (p=.042) and OS (p=.035) than HPV-negative tumors. Multivariate analysis confirmed better DFS and OS of HPV-positive patients independent of age and stage. This reduced risk of progression and mortality in HPV-positive patients was limited to women with FIGO stages I and II tumors (HR=0.26; 95% CI 0.10-0.69; p=0.006).

Conclusions: HPV-positive early stage (FIGO I and II) VaSCCs have a better prognosis than early HPV-negative tumors. HPV detection and/or p16(INK4a) immunostaining can be easily implemented in routine pathology and should be considered as valuable prognostic biomarkers in the study of patients with VaSCC.

Publication types

  • Evaluation Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Alphapapillomavirus / genetics
  • Alphapapillomavirus / isolation & purification*
  • Biomarkers / analysis
  • Carcinoma, Squamous Cell / mortality
  • Carcinoma, Squamous Cell / pathology
  • Carcinoma, Squamous Cell / virology*
  • Cyclin-Dependent Kinase Inhibitor p16 / metabolism
  • DNA Probes, HPV
  • DNA, Viral / isolation & purification
  • Female
  • Follow-Up Studies
  • Humans
  • Middle Aged
  • Multivariate Analysis
  • Neoplasm Staging
  • Papillomavirus Infections / complications*
  • Papillomavirus Infections / diagnosis
  • Polymerase Chain Reaction
  • Prognosis
  • Retrospective Studies
  • Survival Analysis
  • Survival Rate
  • Vaginal Neoplasms / mortality
  • Vaginal Neoplasms / pathology
  • Vaginal Neoplasms / virology*


  • Biomarkers
  • Cyclin-Dependent Kinase Inhibitor p16
  • DNA Probes, HPV
  • DNA, Viral