Human papillomavirus as a favorable prognostic biomarker in squamous cell carcinomas of the vagina.
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.
Institut Clinic of Gynecology, Obstetrics and Neonatology, University of Barcelona, Barcelona, Spain.
Immaculada
I
Alonso
Ana
A
Felix
Aureli
A
Torné
Victoria
V
Fusté
Marta
M
del Pino
Paola
P
Castillo
Juan
J
Balasch
Jaume
J
Pahisa
Jose
J
Rios
Jaume
J
Ordi
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D052685:Alphapapillomavirus / Q000235:genetics / Q000302:isolation & purification*; D015415:Biomarkers / Q000032:analysis; D002294:Carcinoma, Squamous Cell / Q000401:mortality / Q000473:pathology / Q000821:virology*; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000378:metabolism; D015344:DNA Probes, HPV; D004279:DNA, Viral / Q000302:isolation & purification; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008875:Middle Aged; D015999:Multivariate Analysis; D009367:Neoplasm Staging; D030361:Papillomavirus Infections / Q000150:complications* / Q000175:diagnosis; D016133:Polymerase Chain Reaction; D011379:Prognosis; D012189:Retrospective Studies; D016019:Survival Analysis; D015996:Survival Rate; D014625:Vaginal Neoplasms / Q000401:mortality / Q000473:pathology / Q000821:virology*
D015415:Biomarkers; D019941:Cyclin-Dependent Kinase Inhibitor p16; D015344:DNA Probes, HPV; D004279:DNA, Viral