Association between mutant E6 and E7 Human Papilloma Virus Type 16 oncogenes with cyclin D1 expression in cervical cancer: Observational study in Bali

Abstract

Background: Incidence of cervical cancer is higher in low- and middle-income countries, including Indonesia. In Asia, Indonesia ranks second both in mortality and incidence of cervical cancer. Infection by Human Papilloma Virus (HPV) type 16 is a known risk factor, especially with mutations of the E6 or E7 oncogene that lead to chronic infection and malignancy. Increase in cyclin D1 expression is found on cervical cancer cells, including those resistant to chemotherapy. The role of cyclic D1 in increasing cellular proliferation and decreasing apoptosis leads to cervical cancer. Methods: This study was a cross-sectional observational study carried out between August 2020 until August 2021 at Prof. Dr. I.G.N.G. Ngoerah Hospital, Denpasar, Bali, Indonesia. Samples were collected by consecutive sampling of eligible patients. Polyclinic patients newly diagnosed with cervical cancer and who gave informed consent were further examined. We determined their oncogene E6 and E7 HPV type 16 mutation patterns and their association with cyclin D1 expression using contingency coefficient correlation test. Other outcomes including age distribution, parturition history, BMI, pathological type, clinical stage, and E6/E7 mutation characteristics was also recorded. Results: We included 31 eligible subjects with cervical cancer and HPV type 16-positive, divided into mutant E6/E7 (n=12/31; 38.7%) and wild type (n=19/31;61.3%). Primary outcome of association between mutant oncogene and cyclin D1 expression was weak (c=0.283; p-value=0.1). Secondary outcome showed majority of age on 50 years old or over; normal or overweight BMI; squamous cell carcinoma was the most commonly found (n=28/31; 90%); and clinical stage II (n=18/31; 38%) in both groups. Conclusions: This study concluded that there is no association between mutation in the E6/E7 HPV type 16 oncogenes with cyclin D1 expression in patients with cervical cancer.