SCCAg as a Biomarker of Advanced Stage and OS in Limited Resource Setting for Cervical Cancer

Abstract

Elevated serum squamous cell antigen (SCCAg) has been previously correlated with poor survival, extensive tumor involvement, and recurrence for cervical cancer. Failure of serum SCCAg to normalize after treatment completion has also been studied as a poor prognostic indicator. This is the first study describing the association of SCCAg with stage and outcomes in patients diagnosed with cervical cancer in Botswana, in a population with a majority of women who are living with HIV (WLWH). Patients with histologically confirmed cervical cancer were enrolled in a prospective observational study between August 2016 and April 2020 in Botswana. Among all patients undergoing definitive chemoradiation, serum SCCAg was determined at pre-treatment baseline, end of treatment (EOT), and 3-month follow-up (normal reference range 0.3 -1.9 ng/ml). Normalization of SCCAg was defined as return to the reference range after treatment (SCCAg response), and was measured first at EOT; if EOT values were not available, 3-month values were utilized. Patients were staged according to FIGO 2009 criteria, early stage was defined as Stage I-II; while advanced stage was defined as Stage III-IV. Median follow-up was 44 months. A significant cut-off point for baseline and SCCAg response correlated with overall survival (OS) was calculated utilizing a log-rank test RESULTS: Among 234 patients who were diagnosed with histologically confirmed cervical cancer, 73.5% were WLWH (mean CD4 count 466 cells/mL). 92.9% of all cancers were squamous cell carcinoma. 68.8% of patients had elevated SCCAg at time of diagnosis. There was no significant difference in mean baseline SCCAg between WLWH (13.3 ng/mL) and women living without HIV (9.07 ng/mL), p = 0.1052. There was a significant difference seen in mean SCCAg between early (7.9 ng/mL ± SD 13.4) and advanced (18.9 ng/mL, ± SD 29.8) stage disease at diagnosis, p < 0.0001. Baseline SCCAg > 7.9 ng/mL was found to be associated with worse OS (p < 0.001). 5-year OS was significantly different among patients with SCCAg response < = 2.8 (5-year OS 66.2%), vs. SCCAg >2.8 ng/mL (5-year OS 42.4%). There was no significant difference in average SCCAg values between EOT (p = 0.68) and 3-month follow-up (p = 0.24). There was no difference in the proportion of patients who experienced normalized SCCAg by HIV status (p = 0.67). There was no significant difference in SCCAg among WLWH and women living without HIV. Among patients with elevated SCCAg above normal at baseline, SCCAg was associated with early vs. advanced stage disease. Additionally, there was a significant difference seen in overall survival by two measurement points: baseline SCCAg >7.9 ng/mL and response SCCAg >2.8 ng/mL. SCCAg may be utilized as a biomarker in low-resource settings to refine prognosis. Further studies will be needed to determine utility and validation in predicting recurrence risk and/or lymph node metastases.