Genotype Distribution of Human Papillomaviruses & HPV E6/E7 RNA Test for the Detection of High-Grade Cervical Intraepithelial Neoplasia (CIN2+) Among Gynecology Complaints in Northwest Ethiopia
| dc.contributor.advisor | Abebe Tamrat | |
| dc.contributor.advisor | Woldeamanuel Yimtubezinash | |
| dc.contributor.author | Derbie Awoke | |
| dc.date.accessioned | 2025-08-13T08:07:28Z | |
| dc.date.available | 2025-08-13T08:07:28Z | |
| dc.date.issued | 2023-07 | |
| dc.description.abstract | Background: In developing nations, cervical cancer (CC) is the main cause of cancer-related fatalities in women due to the absence of well-established vaccination and screening programs. Exploring the best triage test for women with cervical abnormalities is a timely area of research to advance cervical screening and management. Further, the distinct proportional impact of each HR-HPV on the distribution of cervical lesions varies geographically. There is a shortage of data regarding the clinical value of high-risk human papillomaviruses (HR-HPV) E6/E7 mRNA test and their molecular epidemiology in cervical samples from Ethiopia, particularly in the current study area. Moreover, despite the fact that HR-HPV infection is an essential biological cause of CC, other socio-demographic factors are not well studied in the nation. Therefore, this study aimed to fill these data gaps. Objectives: The aim of the study was to determine the HPV genotype involved in cervical lesions, to evaluate the clinical use of HR-HPV E6/E7 mRNA for the early detection of CIN2+, and to explore factors associated with it among gynecology complaints in northwest Ethiopia. Methods: Between March 2019 and October 2021, a cross-sectional study was carried out at Felege Hiwot Compressive Specialized Hospital (FHCSH). Among women who visited the hospital for gynecological examination, those who were eligible for visual inspection (VIA) based screening were included. Cervical punch samples were obtained by a gynecologist for histological analysis. Cervical swabs collected and analyzed for HR-HPV DNA and HPV E6/E7 mRNA using the Abbott Alinity m system and real-time PCR, respectively at the Institute of Virology, Leipzig University, Germany. Demographic and gynecologic-related history were collected using a structured questionnaire. The distribution and frequency of HR HPVs described using descriptive statistics. Histology was used as the reference test to determine how well the E6/E7 mRNA detected CIN2+. Results: Of the 355 study participants (aged 30 to 80 years), more than half, 211 (59.4%), were unaware of CC, and their previous cervical screening practice was approximately 25%. Cervical biopsies from 41.8% (140/335; 95% CI: 36.6-47.1%) participants were diagnosed as cancer. The proportion of HR-HPV was 53%(188/355; 95%CI: 47.8-58.1%), with 13 different genotypes identified. HPV16 was predominant at 50.4% (95%CI: 29.4-39.2%), followed by HPV31 (9.7%), HPV33 (8.5%), HPV39 and HPV68 (5.8% each), and HPV18 at 4.7%. The iii E6/E7 mRNA test was positive in 35.8% (127/355; 95%CI: 30.0-40.9) of cases for HPV16, 16 & 45. The proportion of positive HPV DNA test results for these three HR-HPVS was 42% (149/355). The total agreement of DNA and mRNA tests in the detection of these HPVs was at 92.7% (95%CI: 89.5-94.9) with a kappa value of 0.821. HPV16, at 108 (85%), was the most common genotype expressing E6/E7 mRNA. The mRNA assay had sensitivity, specificity, positive and negative predictive values (PPV and NPV) of 65.2% (95%CI: 57.5-72.2%), 90% (95%CI: 84.6-93.4%), 85.8% (95%CI: 78.5-91.0%), & 73.6% (95%CI: 67.2-79.1%), respectively for detecting histologically confirmed CIN2+. Specifically, the sensitivity and specificity of this assay in the detection of CIN2+ were 92.7% & 47%, respectively among HPV16, 18, & 45 DNA-positive cases. Likewise, the analytical sensitivity and specificity of the HPV-DNA test were 84.8% & 74.1%, respectively. CC increased steadily with participant age, with women older than 50 years about four times more likely to develop CIN2+ (AOR: 3.68 95%CI: 1.75-7.72, p < 0.001). Similarly, no cervical screening in the past five years (AOR: 2.04; 95%CI: 1.04-4004; p = 0.038), infection with HR-HPVs (AOR: 5.28; 95%CI: 2.66-10.47; p < 0.001) and tested positive for E6/E7 mRNA (AOR: 5.78; 95%CI: 2.73-12.24, p < 0.001) were statistically associated with CIN2+. Conclusions: CC is still a significant issue for women's health in northwest Ethiopia that requires evidence-based interventions. The E6/E7 mRNA test and the HPV DNA test demonstrated good agreement and showed better diagnostic relevance in detecting CIN2+. Therefore, the test can be considered for colposcopy and biopsy triage. In particular, the mRNA test may be regarded as a potential triage for women who are HPV-positive , mainly in regions with a shortage of pathologists and colposcopy facilities. Vaccination and future HPV-based screening methods in Ethiopia should consider the important HR-HPV genotypes identified in such studies. To better assess the HPVs circulating in northwestern Ethiopia, community-based surveys should be conducted. Likewise, to optimize the E6/E7 mRNA analytical sensitivity and specificity , large-scale studies targeting major HR-HPVs should be considered. Finally, in accordance with the WHO recommendation women who are eligible for cervical screening need to be screened with a high-precision test, including HPV-based tests. Keywords: Cervical cancer, CIN2+, HPV E6/E7 mRNA, HR-HPV DNA, northwest Ethiopia | |
| dc.identifier.uri | https://etd.aau.edu.et/handle/123456789/6710 | |
| dc.language.iso | en_US | |
| dc.publisher | Addis Ababa University | |
| dc.subject | Cervical cancer | |
| dc.subject | CIN2+ | |
| dc.subject | HPV E6/E7 mRNA | |
| dc.subject | HR-HPV DNA | |
| dc.subject | northwest Ethiopia | |
| dc.title | Genotype Distribution of Human Papillomaviruses & HPV E6/E7 RNA Test for the Detection of High-Grade Cervical Intraepithelial Neoplasia (CIN2+) Among Gynecology Complaints in Northwest Ethiopia | |
| dc.type | Thesis |