Interaction between the level of human papillomavirus integration and human papillomavirus type on the risk of grade 3 cervical intraepithelial neoplasia or more severe in human papillomavirus integration positive women: A cross‐sectional study

Xin Liu · 2025-10-17

Abstract

Background

The human papillomavirus (HPV) integration test is a novel cervical cancer screening technique. This study aimed to explore the effect of HPV integration level on the risk of grade 3 cervical intraepithelial neoplasia (CIN) or more severe CIN (3+) in HPV integration‐positive women, as well as the interaction between HPV type and HPV integration level on CIN3+.

Method

The HPV integration test was conducted using high‐throughput viral integration detection. The number of HPV integration reads (NHIR) is used to represent the level of HPV integration. Multivariable logistic regression models were used to examine the independent and interaction of the NHIR and the HPV type on CIN3+.

Results

A total of 1053 HPV integration‐positive women enrolled in this study. The percentage of CIN3+ in participants was 32.7%. The risk of CIN3+ increased by 0.9% (odds ratio [OR]: 1.009, 95% confidence interval [CI]: 1.006–1.012) per 10 increases in the NHIR. The risk of CIN3+ in the HPV16/18 group was higher than in the other 12 high‐risk HPV group (OR: 2.875, 95% CI: 2.034–4.064). However, with the elevated NHIR, the risk gap between the two groups gradually narrowed until it disappeared. There is multiplicative ( P  = 0.031) and additive interaction between the NHIR and the HPV type on CIN3+.

Conclusion

There was an interaction between HPV type and NHIR on CIN3+. HPV integration can further assess a patient's risk based on HPV genotyping detection, which is conducive to reducing missed diagnoses. The NHIR might be a potential biomarker for early warning and precise identification of high‐risk CIN lesions.