The value of HPV integration testing for detecting cervical precancerous lesions or malignancies miss-diagnosed by colposcopy-directed biopsies: a cross-sectional study

Objective: To assess the value of human papillomavirus (HPV) integration testing in predicting post-conization pathological upgrading to high-grade squamous intraepithelial lesions or worse (HSIL+) among patients whose colposcopy-directed biopsies revealed no precancerous lesions or malignancies. Design: A cross-sectional cohort study. Setting: Routine clinical work of HPV-associated cervical diseases. Population or Sample: A total of 417 HPV-positive patients whose colposcopy-directed biopsies revealed low-grade squamous intraepithelial lesions or normal (LSIL-) and subsequently underwent diagnostic cervical conization. Methods: The predictive value of HPV integration and cytology for discovering HSIL+ were analyzed and compared. Main Outcome Measures: Postoperative pathological results of HSIL+. Results: Among the 417 patients enrolled, postoperative pathological examinations revealed 91 cases of HSIL and 3 cases of cancer. A total of 76 patients tested positive for HPV integration, while 341 patients tested negative. Higher percentage of HSIL+ was revealed post-conization in those with positive HPV integration compared with those who tested negative (57.9% [46.5-69.3%] vs. 14.7% [11.0-18.3%], P value = 0.000). Compared to high-grade cytology, HPV integration had higher sensitivity (46.8%[36.7-56.9%] versus 24.5%[15.8-33.2%], P value = 0.003) and comparable specificity (90.1%[86.8-93.4%] versus 91.3%[88.3-94.4%]) in predicting postoperative pathological upgrading. The combination of high-grade cytology and HPV integration could detect 90.9% of missed HSIL+, and a double-negative result indicated histological LSIL- in 84.0% cases. Conclusions: HPV integration is a valuable predictor for detecting HSIL+ miss-diagnosed by colposcopy-directed biopsies.