Prevalence Of P16^INK4a Expression In Prevalence Of P16^INK4a Expression In Cervical Histology And Predictive Validity Of P16^INK4a In Cervical Intraepithelial Neoplasia Grade 1 Transformation

Objective: The aim of this study was to 1) determine expression of P16^INK4a in cervical histology and its relation to high-risk HPV(HR-HPV) in some rural Chinese women and 2) evaluate the prognostic significance of P16^INK4a overexpression in cervical intraepithelial neoplasia grade 1 (CIN1) progression.Methods: A total number of 6557 women who had sexual behavior, aged 30-49 years from 3 rural sites were enrolled into study between 2003 and 2005. Vaginal and cervical exfoliated cells were used in hybrid capture 2 (hc2) and cytologic diagnosis. Colposcopy directed biopsy as required were performed on any woman with abnormal cervical liquid based cytology (LBC), a positive visual inspection with acetic acid (VIA), a positive visual inspection with Lugol iodine (VILI) or a positive hc2 test for HR-HPV types. P16^INK4a staining was performed on all CIN, invasive cervical cancer (ICC) and randomly selected normal tissues. The association between P16^INK4a alterations and abnormalities of cervix, as well as the presence of HR-HPV were examined. Women with CIN1 were enrolled in ongoing follow up for 2 years. LBC and hc2 were performed at one-year. At the two-year visit all remaining women were examined by colposcopy and taken biopsy if appropriate. We assessed the correlation between P16^INK4a and CIN1 transformation.Results: The results of baseline screening examination indicated that the prevalence of P16^INK4a staining was 2.67%, 42.69%, 75.47%, 79.59% and 100.00% among non-neoplastic findings, CIN1, CIN2, CIN3 and ICC (χ² =177.91 ,P<0.0001). Spearman rank-order correlation coefficient(rs) showed a high positive correlation (rs=0.62, P<0.0001) between staining and progression. The infection rates of HR-HPV were 15.68%, 76.54%, 88.24%, 95.92% and 100.00% among non-neoplastic findings, CIN1, CIN2, CIN3 and ICC (χ²=204.42,P<0.0001). Spearman rank-order correlation coefficient(rs) showed a high positive correlation (rs=0.65, P<0.0001) between HR-HPV and progression. In CIN group, infection rates of HR-HPV were 96.00% and 65.22% in P16^INK4a positive and negative group. OR value of HR-HPV and P16^INK4a was 12.80(5.19, 31.56). The follow-up results of CIN1 in 2 years showed that there was difference in CIN1 progression between P16^INK4a positive and negative group (χ²=7.61, P=0.006), the risk of CIN1 persistence and progression in P16^INK4a positive group was 2.16(1.24, 3.75) times higher than that in negative group. There was also difference in CIN1 progression between HR-HPV positive and negative group (χ²=8.92, P=0.003), the risk of CIN1 persistence and progression in HR-HPV positive group was 3.62(1.36, 9.65) times higher than that in negative group. The risk of CIN1 persistence and progression in P16^INK4a combined with HR-HPV positive group was 4.30(1.59, 11.61) times higher than that in negative group.Conclusion: There was a strong association between prevalence of P16^INK4a expression and lesion progression. Among all grades of neoplasia there was also strong evidence of a relationship between hc2 positivity and P16^INK4a staining. The follow-up results of CIN1 in 2 years indicated that P16^INK4a, HR-HPV and P16^INK4a combined with HR-HPV positive may be one of the risk factors in CIN1 persistence and progression.