Human papillomavirus: a predictor of better survival in ocular surface squamous neoplasia patients.

BACKGROUND Although human papillomavirus (HPV) has been implicated in the pathogenesis of ocular surface squamous neoplasia (OSSN), no study has so far dealt with the prognostic role of HPV. In this study the presence and significance of HPV in OSSN and its correlation with p16(INK4a) immunoexpression was determined. METHODS HPV was detected by HPV-L1 capsid gene-specific multiplex PCR using PGMY09/11 primers, and genotyping was done by linear array on 64 OSSN patients and 15 conjunctival controls. p16(INK4a) immunoexpression as a marker for HPV presence was also evaluated. RESULTS The HPV genome was detected in 11% of cases by multiplex PCR, and all positives belonged to a high-risk HPV16 genotype. p16(INK4a) Overexpression was seen in 28% (18/64) of cases. Control conjunctival tissues were negative for HPV and p16(INK4a) expression. The presence of HPV was associated with significantly improved disease-free survival (p=0.02) as well as p16(INK4a) overexpression (p=0.001). The sensitivity and specificity of p16(INK4a) as a marker for HPV presence was 86% and 79%, respectively, with a positive predictive value of 33% and a negative predictive value of 98%. CONCLUSIONS The results of this study point towards HPV as a predictor of better survival in a subset of HPV-positive OSSN patients. Although p16(INK4a) immunoexpression is a useful indicator of HPV presence in OSSN, confirmation by multiplex PCR is necessary.