Low-Cost Molecular Biomarker HPV-16/18 E6 Oncoprotein Expression in Cervical Intraepithelial Neoplasia (CIN) and Cervica
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ORIGINAL ARTICLE
Low-Cost Molecular Biomarker HPV-16/18 E6 Oncoprotein Expression in Cervical Intraepithelial Neoplasia (CIN) and Cervical Cancer with Its Relation with Severity of Neoplastic State Rifat Ara1 • Shahana Pervin2
•
Sabera Khatun1 • Umme Shahera1 • Masuda Sultana1 • Mst. Nurunnahar Aktar3
Received: 27 March 2020 / Revised: 24 May 2020 / Accepted: 26 May 2020 Ó Association of Gynecologic Oncologists of India 2020
Abstract Purpose This research was carried out with the intention to see the detection rate of HPV-16/18 E6 oncoprotein expression in different categories of cervical neoplasia and to find out its association with increasing neoplastic state, using lateral flow test ‘‘Onco E6 Cervical Test’’ designed for low-resource settings. Methods A cross-sectional study was conducted at Gynecologic Oncology Outpatient Department (OPD) of Bangabandhu Sheikh Mujib Medical University (BSMMU), Dhaka, Bangladesh, from May 2018 to April 2019. Histopathologically diagnosed CIN I, CIN II, CIN III, and cervical cancer cases of age 21–70 years who were compliant to allow cervical swab collection for E6 oncoprotein test were selected by purposive sampling. Results E6 oncoprotein expression was 4.44% (2/45), 28.57% (4/14), 50% (2/4), and 77.78% (28/36) for CIN I, CIN II, CIN III, and cervical cancer cases, respectively. Thirty-six women of total 99 (N = 99) study participants were found E6 positive (detection rate 36.36%). Type distribution showed 83.33% (30/36) type 16, 13.89% (5/36) type 18, and 2.78% (1/ 36) co-infection with types 16 and 18. Considering CIN I the reference category, E6 oncoprotein expression was found associated with CIN II (OR = 6.95, p = 0.052), significantly associated with CIN III (OR = 18.10, p = 0.026), and highly significantly associated with cervical cancer (OR = 43.57, p \ 0.001). Conclusion Association of E6 oncoprotein expression is significant for CIN III and highly significant for cervical cancer. The presence of E6 oncoprotein expression in CIN lesions can identify true cancer precursors with risk of cancer development in the future and can be utilized in cancer screening program. Keywords Molecular biomarker E6 oncoprotein CIN Cervical cancer
Background Research on genetics of HPV, its association with cervical carcinogenesis, and the outstanding advancement of molecular technology has resulted in the development of new HPV-based molecular assay to upgrade the prevailing
& Shahana Pervin [email protected] 1
Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh
2
National Institute of Cancer Research and Hospital, Mohakhali, Dhaka, Bangladesh
3
Shahid Tajuddin Ahmad Medical College, Gazipur, Bangladesh
methods of cervical cancer screening. HPV viral gene integration with cervical cellular genome causes over-expression of E6 and E7 proteins which are recognized to have high oncogenic properties [1]. With continued expression, E6 oncoprotein interferes with tumor suppressor gene p53 and inhibits apoptosis [2, 3]. It has four C–X– X–C motifs which func
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