Assessment of the applicability of p16 and top2a biomarkers for cervical cancer diagnosis in northern Tanzania

Abstract

Biomarkers provide valuable information for the early detection of cervical cancer. However, they are seldom utilized for the prognosis of cervical cancer in Tanzania, where visual inspection with acetic acid (VIA) or Lugol's iodine (VILI) are being utilized as the standard screening techniques. A retrospective hospital-based cross-sectional study assessing cyclin-dependent kinase inhibitor (p16) and topoisomerase II-alpha (TOP2A) proteins expression was conducted among women seeking cervical cancer care at Kilimanjaro Christian Medical Centre, Tanzania between 1 May, 2017 to 10 May, 2018. A total of 149 studied patients (Mean age: 52.1 ± 12.9 years) were enrolled. Of these, 99 (66.4%) of women seeking care in the period under review were diagnosed with cervical cancer lesions. Moreover, only 145 cervical biopsies met the inclusion criteria for p16 and TOP2A immunohistochemistry (IHC) staining. Upon IHC staining, 103 (71.0%) and 90 (62.1%) were p16 and TOP2A positive, respectively. Histopathological class and p16/TOP2A expression levels were closely associated (Fisher’s exact test, p<0.001). Moreover, p16/TOP2A expression levels were positively correlated with cancerous cervical lesions (Spearman’s rank correlation coefficients = 0.833 and 0.687, p = 0.006 and 0.005, respectively). The age-adjusted odds ratio (AOR) for predicting cervical cancer lesions were independently significant for p16/TOP2A biomarkers in formalin-fixed and paraffin-embedded cervical tissues [p16: AOR=1.142 (95% confidence interval (CI): 1.059–1.232, p<0.001) and TOP2A: AOR=1.046 (95% CI: 1.008–1.085, p=0.015)]. Importantly, the diagnostic performance of p16 was higher than that of TOP2A in the diagnosis of cancerous lesions from non-cancerous cervical lesions (sensitivity: 97.2% versus 77.6%, accuracy: 92.8% versus 87.8%, respectively). Overexpression of TOP2A is linked to the grade of cervical intraepithelial neoplasia in our study, however it does not predict cervical cancer prognosis. Similarly, expression of p16 is associated with histological dysplasia grade and malignancy, suggesting its prognostic significance in the management of cervical cancerous lesions. Further bigger studies are needed to validate their applications in the early diagnosis of cervical cancer.