Persistent human papillomavirus (HPV) infection is recognized as a major risk factor for cervical cancer. Women with persistent HPV and negative cytology are at greater risk of CIN2+ than women with negative infection. The diagnosis becomes more complicated when the woman has a type 3 transformation zone at colposcopy. The aim of this study was to determine the prevalence of CIN2+ in women with persistent HPV, negative cytology and TZ3; how to stratify the risk of CIN2+; and what the best diagnostic strategy is, given TZ3. Methods: In a multicenter retrospective cohort study, we enrolled women with negative cytology and TZ3 among the 213 women referred for colposcopy for persistent HPV. The average age of the women was 53 years; in particular, 83% were postmenopausal women. In the presence of a TZ3, the entire transformation zone cannot be explored, making colposcopy and targeted biopsy useless and inadequate, with great risks of underdiagnosis or missed diagnosis. Women with TZ3 underwent diagnostic LEEP to ensure correct diagnoses. Results: The study highlighted 19% (16/84) of CIN2+ lesions, a higher frequency of non-HPV 16/18 genotypes (76.2%), and 50% of CIN2+ lesions being due to non-HPV 16/18 genotypes. Furthermore, more than half of the women (80.9%) had normal histopathological results in the LEEP sample. Conclusion. Women with viral persistence, negative cytology, and TZ3 have a 19% risk of CIN2+; genotyping helps stratify risk, but extensive genotyping is necessary instead of partial genotyping (16/18), referring to a population of women over 50 years old in which the prevalence of genotypes 16,18 decreases and the prevalence of other genotypes increases; diagnostic LEEP is excessive (only 16 cases of CIN2+ out of 48 cases treated), even though 83% of women had viral clearance after LEEP; p16/Ki67 double staining could be a potential risk marker, which would only highlight women at risk of CIN2+ to undergo LEEP. To individualize the diagnostic workup and treatment and minimize the risk of under diagnosis and overtreatment, future studies should explore the use of extended genotyping and new biomarkers for individual risk stratification.
持续性人乳头瘤病毒(HPV)感染被认为是宫颈癌的主要风险因素。与未感染HPV的女性相比,持续性HPV感染且细胞学阴性的女性发生CIN2+病变的风险更高。当女性在阴道镜检查中出现3型转化区时,诊断变得更加复杂。本研究旨在确定持续性HPV感染、细胞学阴性且伴有TZ3的女性中CIN2+的患病率;如何对CIN2+风险进行分层;以及在TZ3情况下,最佳诊断策略是什么。方法:在一项多中心回顾性队列研究中,我们从213名因持续性HPV感染转诊进行阴道镜检查的女性中,纳入了细胞学阴性且伴有TZ3的女性。这些女性的平均年龄为53岁,其中83%为绝经后女性。在存在TZ3的情况下,无法完整探查整个转化区,使得阴道镜检查和靶向活检变得无效且不充分,存在较高的诊断不足或漏诊风险。因此,伴有TZ3的女性接受了诊断性LEEP手术以确保正确诊断。结果:研究显示,19%(16/84)的女性存在CIN2+病变,非HPV 16/18基因型的感染频率较高(76.2%),且50%的CIN2+病变由非HPV 16/18基因型引起。此外,超过一半的女性(80.9%)在LEEP样本中显示正常的组织病理学结果。结论:伴有病毒持续感染、细胞学阴性及TZ3的女性发生CIN2+的风险为19%;基因分型有助于风险分层,但需要进行广泛的基因分型而非部分分型(16/18),尤其是在50岁以上女性群体中,HPV 16/18基因型的流行率下降,而其他基因型的流行率上升;诊断性LEEP手术可能过度(48例接受治疗的患者中仅16例为CIN2+),尽管83%的女性在LEEP术后实现了病毒清除;p16/Ki67双重染色可能是一种潜在的风险标志物,仅用于识别存在CIN2+风险并需接受LEEP手术的女性。为个体化诊断流程和治疗,并最大程度降低诊断不足和过度治疗的风险,未来研究应探索扩展基因分型和新生物标志物在个体风险分层中的应用。