Bruno Maria Teresa, Valenti Gaetano, Cavallaro Antonino Giovanni, Palermo Ilenia, Aiello Tiziana, Farina Jessica, Panella Marco Marzio, Mereu Liliana
Gynecology and Obstetrics Unit, Department of General Surgery and Medical-Surgical Specialty, Rodolico University Hospital, University of Catania, 95123 Catania, Italy.
Multidisciplinary Research Center in Papillomavirus Pathology, Chirmed, University of Catania, 95123 Catania, Italy.
Cancers (Basel). 2024 May 10;16(10):1816. doi: 10.3390/cancers16101816.
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.
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.
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.
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危险因素。持续性HPV感染且细胞学检查阴性的女性比未感染的女性发生CIN2+的风险更高。当女性在阴道镜检查时出现3型转化区时，诊断会变得更加复杂。本研究的目的是确定持续性HPV感染、细胞学检查阴性且转化区为3型（TZ3）的女性中CIN2+的患病率；如何对CIN2+的风险进行分层；以及在存在TZ3的情况下最佳的诊断策略是什么。
在一项多中心回顾性队列研究中，我们纳入了213名因持续性HPV感染而接受阴道镜检查的女性中细胞学检查阴性且转化区为3型的女性。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，无法对整个转化区进行检查，这使得阴道镜检查和靶向活检无用且不充分，存在漏诊或误诊的巨大风险。患有TZ3的女性接受诊断性利普刀手术以确保正确诊断。
该研究突出显示了19%（16/84）的CIN2+病变，非HPV 16/18基因型的频率更高（76.2%），且50%的CIN2+病变归因于非HPV 16/18基因型。此外，超过一半的女性（80.9%）在利普刀手术样本中的组织病理学结果正常。
病毒持续性感染、细胞学检查阴性且转化区为3型的女性发生CIN2+的风险为19%；基因分型有助于对风险进行分层，但有必要进行广泛的基因分型而非部分基因分型（16/18），这适用于50岁以上的女性群体，其中16、18基因型的患病率降低而其他基因型的患病率增加；诊断性利普刀手术过度（在48例接受治疗的病例中只有16例CIN2+），尽管83%的女性在利普刀手术后病毒清除；p16/Ki67双重染色可能是一种潜在的风险标志物，它只会突出显示有CIN2+风险的女性接受利普刀手术。为了使诊断检查和治疗个体化并将漏诊和过度治疗的风险降至最低，未来的研究应探索使用扩展基因分型和新的生物标志物进行个体风险分层。
