Associations between the expression of SCCA, MTA1, P16, Ki‑67 and the infection of high‑risk HPV in cervical lesions

Abstract

The application of detection technologies for human papillomavirus (HPV) has increased the resection rate for cervical intraepithelial neoplasia and early cervical cancer types. However, a large number of patients still present with advanced cervical cancer upon diagnosis. Therefore, to find a marker for the early diagnosis of cervical cancer, the present study investigated the expression profiles of squamous cell carcinoma antigen (SCCA), tumor metastasis related factor-1 (MTA1), the multiple tumor suppressor gene P16, and the nucleus-associated antigen Ki-67 in cervical lesions, and evaluated the association between the four proteins and the infection of high-risk (HR)-HPV in cervical lesions. The rate of SCCA expression gradually increased with the progression of cervical lesions, but the increase in SCCA expression levels from low-grade squamous intraepithelial lesions (LSIL) to high-grade squamous intraepithelial lesions was not significant (P= 0.197). The positive rate of MTA1 expression gradually increased with the development of cervical lesions, but the increase from chronic cervicitis to LSIL was not significant (P=0.258). The positive rates of P16 and Ki-67 expression exhibited significant increasing trends with the progression of cervical lesions. The expression ratio of SCCA between HR-HPV infection and non-infection groups was not statistically significant (P=0.38), but the expression ratios of MTA1, P16 and Ki-67 between HR-HPV infection and non-infection groups were statistically significant (P<0.05). These results demonstrated that the expression of SCCA, MTA1, P16 and Ki-67 increased gradually with the severity of cervical lesions. In addition, there was a positive association between the expression levels of MTA1, P16 and Ki-67 and the infection of HR-HPV in cervical lesions. Therefore, SCCA, MTA1, P16 and Ki-67 may be used to enhance the diagnostic accuracy for cervical lesions.

Molecular markers for cervical cancer screening

“…The most relevant clinical use of immunoassays in cervical cancer diagnostics is based on IHC, where antibodies are used to visualize specific proteins on cells or tissues followed by their microscopic analysis. IHC staining of p16, an inhibitor of cyclin-dependent kinases, and Ki-67, a cell proliferation marker, showed potential for improving diagnostic accuracy [41,42]. The p16/Ki-67 dual staining technology is more sensitive than cytology in detecting CIN2+ in hrHPV-positive women and can be used for triage after a positive hrHPV test to guide the decision on how to follow-up, for example, by colposcopy [43,44].…”

Cervical Neoplasia: Papillomavirus Infection and Resistance to Anti Tumor Immunity

“…Their proportions are much greater when the studies concern patients with clinically identifiable lesions [50]. But in cases where studies are done to screen a population for cervical cancer, the frequencies of intraepithelial neoplasms are relatively low [21].…”

“…The most desired indirect biomarker of Papillomavirus infection in cervical intraepithelial neoplasia is P16 INKa; Its overexpression has been shown in several studies to be as associated with intraepithelial neoplasia of the cervix secondary to high carcinological Papillomavirus infection [18][19][20]. Several other authors show that the biomarkers Ki67 and TP53 are also considered to be a marker of high oncogenic Papillomavirus infection in intraepithelial neoplasia of the cervix [21][22][23]. Further research is focusing on identification of viral oncopreteins E6 and E7 as markers of high-risk Papillomavirus infection in intraepithelial neoplasia [24][25][26].…”

p16INKa and Ki67 expression in different grades of cervical intraepithelial neoplasm in relation to HPV genotypes

“…Cervical carcinoma is the third (Arbyn, 2011) or the fourth (Arbyn, 2020;Han, 2020) most common malignancy in women worldwide accounting for about 7.9% of all cancers. It is considered the most common cause of death among women in developing countries (Arbyn, 2011).…”