Sustova Pavla, Engesæter Birgit, Øvestad Irene Tveiterås, Gudlaugsson Einar G, Ghiasvand Reza, Skaland Ivar, Baak Jan P A, Tropé Ameli, Janssen Emiel A M, Munk Ane Cecilie
Department of Laboratory Medicine, St. Olav's Hospital, Trondheim University Hospital, 7006 Trondheim, Norway.
Department of Clinical and Molecular Medicine, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology, 7030 Trondheim, Norway.
Int J Mol Sci. 2025 May 28;26(11):5205. doi: 10.3390/ijms26115205.
Cervical intraepithelial neoplasia (CIN) is caused by human papillomavirus (HPV); however, factors such as HPV genotype and individual immune response may also contribute to its development. The loop electrosurgical excision procedure (LEEP) is a treatment for high-grade cervical intraepithelial neoplasia (CIN), as approximately 30% of these cases may progress to cancer. However, 20-40% of cases will regress spontaneously. HPV16 infection constitutes the highest risk for progression to cervical cancer and a lower probability of regression. Knowledge regarding the regression of lesions caused by other high-risk genotypes alone or in association with biomarker expression and lesion length has been limited. In the present study, the regression rates of high-grade squamous intraepithelial lesions were calculated. Twenty-one percent of the 161 women diagnosed with CIN2-3 on colposcopy-directed biopsies exhibited regression (defined as CIN1 or less) in the subsequent cone excisions. The mean interval between biopsy and treatment was 113 days (range of 71-171). High-grade lesions of the squamous epithelium caused by HPV16, together with lesions caused by HPV31, 52 and 58, showed significantly lower regression rates (HR 0.54, 0.22-0.75; low-regression group) than lesions caused by HPV18, 33, 35, 39, and 45 (HR 2.85, 1.54-5.28; high-regression group). A multivariate analysis of HPV genotypes, epithelial expressions of pRb and p53, immune cell proportions in the stroma (CD4/CD25 and CD4/CD8), and lesion lengths correctly predicted regression in 78% (Harrell's C). A Harrell's C value of 82% for the low-regression group indicates that different HPV genotypes or groups, together with divergent patterns of tumor suppressors, immune cells, and lesion size, can give prognostic information regarding the outcome of CIN2-3.
宫颈上皮内瘤变（CIN）由人乳头瘤病毒（HPV）引起；然而，HPV基因型和个体免疫反应等因素也可能促使其发展。环形电切术（LEEP）是治疗高级别宫颈上皮内瘤变（CIN）的一种方法，因为这些病例中约30%可能进展为癌症。然而，20%-40%的病例会自发消退。HPV16感染进展为宫颈癌的风险最高，消退的可能性较低。关于由其他高危基因型单独引起的病变或与生物标志物表达及病变长度相关的病变消退的知识一直有限。在本研究中，计算了高级别鳞状上皮内病变的消退率。在经阴道镜引导活检诊断为CIN2-3的161名女性中，21%在随后的锥形切除术中出现消退（定义为CIN1或更低）。活检与治疗之间的平均间隔为113天（范围71-171天）。由HPV16引起的鳞状上皮高级别病变，与由HPV31、52和58引起的病变一起，显示出的消退率（风险比0.54，0.22-0.75；低消退组）显著低于由HPV18、33、35、39和45引起的病变（风险比2.85，1.54-5.28；高消退组）。对HPV基因型、pRb和p53的上皮表达、基质中的免疫细胞比例（CD4/CD25和CD4/CD8）以及病变长度进行多变量分析，正确预测消退的准确率为78%（Harrell氏C统计量）。低消退组的Harrell氏C值为82%，表明不同的HPV基因型或组，连同肿瘤抑制因子、免疫细胞和病变大小的不同模式，可以提供关于CIN2-3结果的预后信息。
