Association of human papillomavirus L1 capsid protein with koilocytosis, expression of p16, and Ki-67, and its potential as a prognostic marker for cervical intraepithelial neoplasia.

Objective: To study the relationship between human papillomavirus (HPV) L1 capsid protein (L1) and koilocytosis on ThinPrep cytology tests (TCTs) and the association of HPV L1 with p16 and Ki-67 expression in their corresponding biopsies.

Study Design: TCTs of 75 patients with high-risk HPV infection were studied for cytologic features of koilocytosis and for HPV L1 expression using combined detection of in situ hybridization and immunocytochemistry. All TCTs had follow-up biopsies on which p16 and Ki-67 were confirmed by immunostaining.

Results: Of 75 TCTs, 45 expressed HPV L1, while 23 displayed koilocytosis. All TCTs with koilocytosis expressed HPV L1. HPV L1 was lost in 23.3% of cervical intraepithelial neplasia (CIN) I, 16.7% of CIN II, and 60% of CIN III or higher (carcinoma in situ including suspected minor infiltration), categorized by biopsy, and the difference among CIN grades was statistically significant (chi2, p = 0.015). Expression scores of p16 and Ki-67 were higher in L1 negative cases than in positive cases (1.63 vs. 1.54 for p16; 1.53 vs. 1.32 for Ki-67); however, the difference was not significant (Mann-Whitney test: p = 0.57 for p16, p = 0.27 for Ki-67).

Conclusion: HPV L1 expression was significantly associated with koilocytosis on TCT, and loss of L1 was associated with increase in CIN grade but not with p16 or Ki-67 expression. Our study suggests that HPV L1 is a more sensitive method than koilocytosis for detecting active HPV infection. Detection of HPV L1 on TCTs of high-risk HPV-infected patients can be helpful in risk assessment and prognostic prediction of CIN.