Effectiveness of HPV E6/E7 mRNA Test to Triage Primary Screen Positive Women in Cervical Cancer Screening

mRNA-Based Triage in Cervical Screening

Abstract

Background: Marked advancements in molecular technology and better understanding of the natural history of Human Papillomavirus (HPV) have significantly contributed to the introduction of molecular biomarkers in cervical cancer screening in recent years. The detection of highly sensitive HPV DNA and the highly specific HPV E6/E7 mRNA are now widely utilized in developed countries for cervical cancer screening. Among these, the HPV E6/ E7 mRNA test is considered more specific for identifying precancerous cervical lesions.

Objective: To evaluate the effectiveness of the HPV E6/E7 mRNA test as a triage tool for screening of cervical cancer in primary screen positive women by VIA (visual inspection with acetic acid) or Pap smear (cytology) or HPV DNA test.

Methods: This cross-sectional observational study was conducted in the colposcopy clinic of the National Centre for Cervical & Breast Cancer Screening & Training, Bangladesh Medical University (BMU) in collaboration with the Department of Virology, BMU, Dhaka, Bangladesh, from October 2023 to September 2024. This study included 150 women by consecutive sampling who tested positive on any primary cervical cancer screening method (VIA/Cytology/HPV DNA) and were referred to the colposcopy clinic of BMU. After collecting cervical sample from each enrolled subject, colposcopy and colposcopy directed biopsy was performed. HPV E6/E7 mRNA test was performed on cervical sample in virology department of BMU. Presence of E6/E7 mRNA predicts the precancerous & early invasive lesion. Colposcopy reported normal or precancerous lesion (CIN 1, 2, 3). Finally, histopathology on biopsy material confirmed it as normal (e.g cervicitis) or precancerous (CIN 1, 2, 3) or cancerous (e.g invasive carcinoma or carcinoma in situ). All data were processed and analysed using 26 version of SPSS. Diagnostic efficacy of HPV E6/E7 mRNA and colposcopy for detection of pre-cancerous/ cancerous cervical lesion were calculated taking histopathology as gold standard.

Results: The majority of participants were aged 30–39 years (45.3%) and multiparous (87.3%). Colposcopy revealed cervical intraepithelial neoplasia 1 (CIN I) in 60% of cases, while histopathology showed chronic cervicitis (54.67%) and CIN I (30.67%) as the most common findings. HPV E6/E7 mRNA was overexpressed in 15% of cases. Among E6/E7 mRNA-positive patients, 78.3% had biopsy-confirmed precancerous and cancerous lesions, compared to 39.37% in the mRNA-negative group. The E6/E7 mRNA test showed high specificity (93.9%), high PPV (78.3%) and overall accuracy 63.3% for detecting precancerous and early invasive lesions, with low sensitivity of 26.5%. Colposcopy showed higher sensitivity (94.12%) but very low specificity (8.54%) and low accuracy (47.33%) in this regard. Compared to colposcopy; the E6/E7 mRNA test provided more reliable diagnostic accuracy (63.3% vs 47.33%) for detecting precancerous and early invasive lesions of cervix.

Conclusion: The findings obtained from the study, emphasize the importance of integrating HPV E6/E7 mRNA molecular testing into routine cervical cancer screening programs as a triage test due to its high specificity, PPV and accuracy compared to colposcopy for identifying clinically significant precancerous and early invasive lesions of cervix. Therefore, the HPV E6/E7 mRNA test may serve as an effective triage tool before doing colposcopy for identifying clinically significant precancerous cervical lesions and contributing to the prevention of cervical cancer. Thus it also can minimize colposcopy referral and over treatment.

Bangladesh Medical Res Counc Bull 2025;51(3): 123-130