The value of high-risk HPV E6/E7 mRNA test positivity with NILM cytology in detecting cervical squamous intraepithelial lesions and cervical cancer

Abstract Background: The number of patients who use E6/E7 mRNA for HPV testing is increasing yearly in China.However, there is a lack of uniform clinical standards and guidelines for the management of HPV E6/E7 mRNA-positive patients.This study aimed to assess the value of an HPV E6/E7 mRNA assay and HPV 16 18/45 genotype assay combined with age stratification for triaging women negative for intraepithelial lesions or malignancy (NILM) cytology. Methods: From January 2017 to December 2021, a total of 162309 eligible women underwent cervical cancer screening at the Affiliated Hospital of Jining Medical University, China. Excluding those with negative HPV E6/E7 mRNA, abnormal and unsatisfactory cytology, and those who failed to undergo colposcopy, 6845 women were ultimately included in our study. We analysed the triage guidance for different subtypes of HPV in the presence of NILM cytology. Results: Among 162309 women, 19834 (12.2%) were positive for HPV E6/E7 mRNA. Of the 6845 women included in the study, 1941 (28.4%), 561 (8.2%), 55 (0.8%) and 4,288 (62.6%) tested positive for HPV 16, HPV 18/45, HPV16/18/45 or other HR-HPV genotypes, respectively. The proportions of LSIL+ (including LSIL, HSIL and ICC) and HSIL+ (including HSIL and ICC) pathological results in the HPV 16/18/45+ group were 57% and 34.1%, respectively, higher than 36.3% and 11% in the other HR-HPV+group (c2 =653.214, P<0.001). The percentages of LSIL+ and HSIL+ in the HPV16+ group (61.3% and 42.8%, respectively) and HPV16+/18/45+ group (76.3% and 41.9%, respectively) were much higher than those in the HPV18+ group (40.6% and 13.1%, respectively) (P<0.001). However, there was no significant difference in the percentage of histopathological results between the HPV16+ group and HPV16+/18/45+ groups (P>0.05). The above results were consistent after stratification according to age. Conclusions: The rate of histopathological abnormalities was still high for the other HR-HPV subtypes with NILM cytology, although the rate of histopathological abnormalities was much higher for the HPV 16/18/45 positive subtypes. Therefore, colposcopy should be performed in women with HPV E6/E7 mRNA positivity and NILM cytology, regardless of age and HPV genotype.