Evaluation of HPV E6/E7 mRNA Detection in Clinically Suspected Cases of Cervical Cancer with Abnormal Cytology: Time to Upgrade the Screening Protocols

Abstract

Background Human papillomavirus (HPV) E6/E7 mRNA tests determine the oncogenic activity of the virus and represent a good clinical biomarker for predicting the risk of cervical cancer. So, the present study was conducted to know the role of HPV E6/E7 mRNA as a predictive biomarker for cervical carcinoma. Methodology The present study was conducted on 55 clinical samples of cervical scrapings and biopsy from the clinically suspected cases (based on signs and symptoms) of cervical cancer having abnormal PAP smear. The samples were processed in three steps—(1) HPV DNA detection, (2) HPV E6/E7 mRNA detection, and (3) histopathological analysis. Results Out of a total of 55 patients, 16 (29.09%) were positive for both HPV E6/E7 mRNA and HPV DNA and six were positive for only HPV DNA. So, a total of 22 (40%) patients were positive for HPV DNA. Out of these 22 samples, 10 (45.5%) were of HPV-16, six (27.3%) were of HPV-18, four (18.2%) were of HPV-31, and two (9.1%) were of HPV-45. Out of total 16 patients positive for HPV E6/E7 mRNA, 10 (62.5%) were of genotype 16 and six (37.5%) were of genotype 18. The patients who were found positive for HPV 31 and 45 genotypes did not have E6/E7 mRNA expression. On colposcopic-guided biopsy, among these 16 samples, eight (50%) were diagnosed with invasive squamous cell carcinoma, six (37.5%) with cervical intraepithelial neoplasia grade 3 (CIN3), and two (12.5%) with CIN2. Out of those six patients in whom only HPV DNA was positive, five had normal biopsy findings and one had CIN1. Conclusion The present study suggests that HPV E6/E7 mRNA detection could be more reliable than DNA testing for predicting the risk of progression of HPV-induced cervical lesions to cervical carcinoma and it can be used as a non-invasive tool for triage and patient follow-up.

Long-Term Follow-Up Outcomes in Women with In Situ/Microinvasive Adenocarcinoma of the Uterine Cervix Undergoing Conservative Treatment—Cervical Adenocarcinoma Study Group Italian Society of Colposcopy and Cervico-Vaginal Pathology

“…An additional test, such as APTIMa mRNA, has shown good accuracy in identifying glandular lesions of the uterine cervix [ 38 ]. In this case, detecting HPV RNA E6/E7 expression is a better expression of the virus’s oncogenic activity [ 39 ]. Finally, the role of the study of HPV DNA methylation is emerging with satisfactory results in improving the prediction for cervical glandular lesions [ 40 , 41 ].…”

MSSRCA Powered Sensitive Point-of-Care Detection of HPV mRNA for Cervical Cancer Screening

“…Therefore, accurate and affordable point of care testing (POCT) technologies for sensitive detection of oncogenic nucleic acids from HPV infection are critical essential to achieve health equality [3][4][5] . Comparing HPV DNA, HPV mRNA (especially E6/E7 mRNA) in high risk types is evidenced to be a more speci c nucleic acid biomarker for the identi cation of women at risk of developing cervical carcinoma [6][7][8][9] . Current commercial methods for HPV mRNA testing for high-risk types mainly include in-situ hybridization HPV tests and nucleic acid ampli cation tests (NAAT) 10 .…”