High-Grade Cervical Intraepithelial Neoplasia: Impact of Colposcopic Lesion Area on Systemic Immune Responses.

Abstract

Background: The progression of high-grade cervical intraepithelial neoplasia (CIN) and cervical cancer is accompanied by a reduction in the immune response. The objectives of the study were to determine whether colposcopic lesion area is associated with serum levels of cytokines IL (interleukin) -1, IL-6, IL-8, IL-10, IL-12 and TNF-α in precursor lesions of cervical cancer.

Methods: The study population comprised patients with high-grade squamous intraepithelial lesion who had undergone colposcopy, cervical biopsy, and measurements of serum cytokines by ELISA (Enzyme-Linked Immunosorbent Assay). Genotyping for HPV (human papillomavirus) 16, 18, 45 and 52 was performed by PCR (Polymerase Chain Reaction). ROC (Receiver Operating Characteristic) curves were calculated to determine whether there existed a cut-off value for serum cytokines in patients with colposcopic lesion area smaller vs larger than 1 cm². For cytokines with significant results, these cut-off values were used to perform the multivariable analysis.

Results: There were 71 patients with CIN 2/3. ROC curves were calculated to verify a cut-off value for serum cytokine levels that could be used to distinguish between lesion areas <1 cm2 vs ≥1 cm2. Values with statistical significance were IL-1 >13.3 pg/mL and IL-12 ≤349.6 pg/mL. In the multivariable analysis, the independent variables associated with colposcopic lesion area greater than 1cm² were IL-1>13.3 pg/mL and IL-12 ≤349.6 pg/mL [OR (95% CI) = 10.10 (1.50-67.96); OR (95% CI)=10.70 (1.17-97.45), respectively].

Conclusion: Although CIN 2/3 is a local uterine cervix lesion, there is a systemic immunological response. Our results are unprecedented and could be the target of new important studies in public health and cervical cancer prevention.