Characterization of p16 and E6 HPV-related proteins in uterine cervix high-grade lesions of patients treated by conization with large loop excision.

Cervical cancer and its precursor lesions represent a significant public health problem for developing and less-developed countries. Cervical carcinogenesis is strongly correlated with persistent high-risk human papillomavirus (HPV) infection, which is mostly associated with expression of the p16 and E6 HPV-related proteins. The aim of this present study was to determine the expression of the p16 and E6 proteins in females with high-grade lesions treated with conization, and to discuss the role of these proteins as prognostic markers following treatment. In total, 114 females were treated for high-grade cervical intraepithelial neoplasia (CIN, grades 2/3) by conization with large loop excision of the transformation zone (LLETZ). Following surgery, the patients returned within 30-45 days for post-operative evaluation. A follow-up was conducted every 6 months for 2 years. At each follow-up appointment, a Pap smear, colposcopy and HPV DNA test were performed. E6 and p16 immunohistochemical tests were conducted on the surgical specimens. The positive expression of p16 was correlated with the presence of lesions with increased severity in the surgical specimens (P= 0.0001). The expression of E6 did not demonstrate the same correlation (P=0.131). The HPV DNA hybrid, collected in the first post-operative consultation as a predictor of the cytological abnormalities identified at the 24-month follow-up assessment, presented a sensitivity of 55.6%, a specificity of 84.8%, a positive predictive value of 33.3% and a negative predictive value of 93.3%. The role of p16INK4A as a marker of CIN was also demonstrated; the expression of p16 and E6, however, did not appear to be of any prognostic value in predicting the clearance of high-risk HPV following conization. A negative hybrid capture test was correlated with a disease-free outcome.

Evaluation of the combination of cytology and hybrid capture to safely predict the high-grade lesion status of patients treated with conization with large loop excision of the transformation zone.

OBJECTIVES: This study aimed to verify whether human papillomavirus (HPV) testing after conization treatment has some potential usefulness for predicting patients' outcome. STUDY DESIGN: One hundred and twenty women were treated for HSIL by conization with large loop excision of the transformation zone (LLETZ). Cytology, colposcopy-guided biopsy, and hybrid capture 2 (HC2) HPV DNA tests were performed before the surgical procedure and every 6 months for 2 years at follow-up. RESULTS: More than 90% of the patients tested positive for high-risk HPV prior to the surgical intervention. Six months after the cervical conization, 74.75% of the patients tested negative for high-risk HPV DNA, and 19.41% were positive. Of the women who were HC2 negative, 72 showed normal cytological smears, 3 ASC-US, 2 LSIL, and 1 HSIL. Of those who were HC2 positive, 8 showed normal smears, 2 ASC-US, 2 ASC-H, 5 LSIL, and 1 case had HSIL, AGC, and squamous cells invasive carcinoma. Clinically, the HSIL case with a negative HPV test did not show any sign of high-grade lesions, and the clinical follow-up did not show residual lesions. CONCLUSIONS: Negative HPV tests correlated with freedom from high-grade disease after 2 years of postconization follow-up, which strongly suggests that negative HPV tests predict the absence of cervical disease.