Association of foxp3 and p16ink4a serum expression with grades and treatment outcomes of cervical squamous intraepithelial lesions in south western Uganda.

Abstract

Abstract

Background: Immunohistochemical expression of P16ink4A and FOXP3 is associated with increasing grades of cervical intraepithelial lesions. We determined the prevalence of cervical intraepithelial lesions and associated factors, the association between serum biomarkers P16ink4A and FOXP3 concentrations and cervical intraepithelial lesions, and the diagnostic accuracy of serum biomarkers P16ink4A and FOXP3 in the detection of cervical intraepithelial lesions, and treatment outcomes among women attending the cervical cancer clinic at Mbarara Regional Hospital (MRRH), South Western Uganda.

Methods: We conducted a cross sectional study (n=364), two case control studies (n=270 and n=279) and a 12 months prospective cohort study (n=180). Participants included women seeking cervical cancer screening and testing services at the cervical cancer clinic of MRRH, from April 1 2022 to March 30, 2024. We collected clinical and demographic data, collected blood samples and measured serum P16ink4A and FOXP3 concentrations using quantitative ELISA kits from Elabscience Biotechnology. All Pap smears were microscopically examined by a laboratory scientist together with a pathologist following the Bethesda grading system (2014). All cases were confirmed with cytology and/or histology and statistical analyses were done in STATA version 17.

Results: The prevalence of cervical intraepithelial lesions was 6.6%. We observed increased odds of cervical intraepithelial neoplasia (CIN) for P16ink4A and a significant reduction in odds of cervical cancer (CC) for serum P16ink4A. Also, increased FOXP3 concentrations increased the chances of CC by 2 times. FOXP3 concentration of >0.0545ng/ml showed moderate sensitis (12.22% and 57.78%) and specificity (68.89% and 68.89%) for detection of CIN and CC from healthy controls respectively. P16ink4A concentration of >0.946ng/ml showed moderate sensitivities (50.00% and 60.00%) and specificities (56.67% and 55.56%) for the detection of CIN and CC from healthy controls respectively. A combination of elevated FOXP3 and P16ink4A showed high specificity of 83.33%. The mean relative risk for follow-up serum FOXP3 among participants with persistent and progressed lesions was 1.34 and 27.82 respectively while that of P16ink4A among persistent and progressed lesions was 5.16 and 0.44 respectively.

Conclusions: The prevalence of cervical intraepithelial lesions was lower than global estimates. Serum P16ink4A and FOXP3 concentrations were observed to not only be associated with, but also highly specific for detection of cervical lesions and their persistence and progression. Quantitative measurement of circulating P16ink4A and FOXP3 may aid in diagnosis as well as prediction of persistence and progression of cervical lesions; and their combination has a high potential to be applied for diagnosis rather than screening for cervical lesions.