Distribution and diagnostic value of single and multiple high‐risk HPV infections in detection of cervical intraepithelial neoplasia: A retrospective multicenter study in China

Abstract The risk associated with single and multiple human papillomavirus (HPV) infections in cervical intraepithelial neoplasia (CIN) remains uncertain. This study aims to explore the distribution and diagnostic significance of the number of high‐risk HPV (hr‐HPV) infections in detecting CIN, addressing a crucial gap in our understanding. This comprehensive multicenter, retrospective study meticulously analyzed the distribution of single and multiple hr‐HPV, the risk of CIN2+, the relationship with CIN, and the impact on the diagnostic performance of colposcopy using demographic information, clinical histories, and tissue samples. The composition of a single infection was predominantly HPV16, 52, 58, 18, and 51, while HPV16 and 33 were identified as the primary causes of CIN2+. The primary instances of dual infection were mainly observed in combinations such as HPV16/18, HPV16/52, and HPV16/58, while HPV16/33 was identified as the primary cause of CIN2+. The incidence of hr‐HPV infections shows a dose–response relationship with the risk of CIN ( p for trend <0.001). Compared to single hr‐HPV, multiple hr‐HPV infections were associated with increased risks of CIN1 (1.44, 95% confidence interval [CI]: 1.20–1.72), CIN2 (1.70, 95% CI: 1.38–2.09), and CIN3 (1.08, 95% CI: 0.86–1.37). The colposcopy‐based specificity of single hr‐HPV (93.4, 95% CI: 92.4–94.4) and multiple hr‐HPV (92.9, 95% CI: 90.8–94.6) was significantly lower than negative (97.9, 95% CI: 97.0–98.5) in detecting high‐grade squamous intraepithelial lesion or worse (HSIL+). However, the sensitivity of single hr‐HPV (73.5, 95% CI: 70.8–76.0) and multiple hr‐HPV (71.8, 95% CI: 67.0–76.2) was higher than negative (62.0, 95% CI: 51.0–71.9) in detecting HSIL+. We found that multiple hr‐HPV infections increase the risk of developing CIN lesions compared to a single infection. Colposcopy for HSIL+ detection showed high sensitivity and low specificity for hr‐HPV infection. Apart from HPV16, this study also found that HPV33 is a major pathogenic genotype.