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

Roncaglia,Maria   Teresa; Fregnani,José  Humberto T.G.; Tacla,Maricy; De Campos,Silvana  Gisele Pegorin; Caiaffa,Hélio   Hehl; Ab'Saber,Alexandre; Da Motta,Eduardo   Vieira; Alves,Venâncio  Avancini Ferreira; Baracat,Edmund  C.; Filho,Adhemar   Longatto

doi:10.3892/ol.2013.1356

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

Authors:
- Maria Teresa Roncaglia
- José Humberto T.G. Fregnani
- Maricy Tacla
- Silvana Gisele Pegorin De Campos
- Hélio Hehl Caiaffa
- Alexandre Ab'Saber
- Eduardo Vieira Da Motta
- Venâncio Avancini Ferreira Alves
- Edmund C. Baracat
- Adhemar Longatto Filho
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Affiliations: Department of Gynecology, Faculty of Medicine, São Paulo University, Cerqueira César, São Paulo, Brazil , Center for Researcher Support, Barretos Cancer Hospital, Pio XII Foundation, Barretos, São Paulo, Brazil, Molecular Oncology Research Center, Barretos Cancer Hospital, Barretos, São Paulo, Brazil, Laboratory of Medical Investigation (LIM) 03, Clinics Hospital Faculty of Medicine, São Paulo University, Cerqueira César, São Paulo, Brazil , Department of Pathology, Clinics Hospital, São Paulo University, Cerqueira César, São Paulo, Brazil, Laboratory of Medical Investigation (LIM) 14, Department of Pathology, Faculty of Medicine, São Paulo University, Cerqueira César, São Paulo, Brazil
Published online on: May 20, 2013 https://doi.org/10.3892/ol.2013.1356
Pages: 63-68

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Abstract

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.

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