We confirmed the usefulness of P16 immunocytochemistry combined with ISH and HPV genotyping as ancillary molecular-biological tests of LBC specimens for identifying patients at high risk of cervical cancer.
The methylation of the p16 gene promoter could significantly reduce p16 expression, losing its tumor suppressor activity and promoting the development of cervical cancer.
Moreover, p16 protein was associated with CIN grade and lymph node metastases in cervical cancer (all P<0.05); survivin protein was also related with clinical stages, CIN grade and lymph node metastases (all P<0.05); the p16 and survivin expressions were positively correlated with cervical cancer (r=0.854, P<0.001), and associated with poor prognosis of cervical cancer.
We aimed to investigate the expression and clinical significance of cyclin-dependent kinase inhibitor 2A (P16<sup>INK4A</sup>), sex determining region Y-box 2 (SOX2), and Aldehyde dehydrogenase 1 family, member A1 (ALDH1A1) in cervical cancer treated with radiotherapy and cervical cell line models.
However, there is little information on the possible impact of the HPV genotype and p16 immunostaining on the clinicopathological features or their prognostic value in cervical carcinoma.
Immunohistochemical p16ink4a expression is associated with HPV infection in HSIL and cervical cancer, suggesting a role of p16 as a biomarker of HPV-associated cervical lesions.
Women seen at Pérola Byington Hospital, São Paulo, Brazil, with histologically confirmed cervicitis (n = 31), cervical intraepithelial neoplasia (CIN) 1 (n = 30), CIN 2,3 (n = 30), and cervical cancer (n = 7) had also cervical material collected for liquid-based cytology, human papillomavirus Hybrid Capture 2 (HC2) test, and p16 and FHIT immunohistochemical reactions.
P16INK4a hypermethylation was significantly associated with the increased risk of LSIL, HSIL and CC, with the pooled ORs of 3.26 (95% CI: 1.86-5.71), 5.80 (95% CI: 3.80-8.84) and 12.17 (95% CI: 5.86-25.27), respectively.
The expression of p16(INK4A) protein was immunohistochemically studied in these cases and in five HPV-positive and one HPV-negative cervical cancer cell lines.
The p16ink4a overexpression is an indicator of an aberrant expression of viral oncogenes and may serve as a marker for early diagnostic of cervical cancer.
Carcinogenesis of cervical cancer has been investigated, and p16(INK4a) overexpression in squamous cell carcinoma of the cervix has been reported as a result of infection by human papillomavirus (HPV) (eg, HPV 16), and the consequence of the retinoblastoma (Rb) protein inactivation by HPV E7 protein.
Deletions or point mutations in the p15INK4B or p16INK4A gene may not be required for the development of HPV-positive cervical cancer or for establishment of cervical cancer cell lines.