Chronic Infectious Diseases and Cancer Division, Center for Research on Infectious Diseases, Instituto Nacional de Salud Pública (INSP), Cuernavaca, Morelos, Mexico.
CONACYT-INSP, Cuernavaca, Morelos, Mexico.
BMC Infect Dis. 2018 Nov 19;18(1):582. doi: 10.1186/s12879-018-3490-1.
Cervical cancer (CC) is caused by a persistent infection of high-risk human papillomavirus (HR-HPV). While most HPV infections are transient, persistent HPV infections are a significant health problem in Mexico. With an estimated HPV prevalence of 10% among women in reproductive age, approximately 25% of these women present at least a positive result in triage test, which according to previous studies is expected to be confirmed as positive CIN-2/3. The immune system has a key role in the natural history of HPV infection; alterations in the cellular immune response are responsible for the failure to eliminate HPV. The objective of this project is to assess the prognostic value of detecting immune markers (IL-10, IL-4, TGFβ1, IFNγ, IL-6, and TNFα), the expression of HPV-HR E6/E7 proteins, and the viral load at the cervical level with respect to the persistence or clearance of HR-HPV infection, and the regression or progression of a cervical premalignant lesion.
A dynamic cohort study is being conducted in women with colposcopic, cytological, and histopathological results negative for squamous intraepithelial lesion (SIL) in the cervix and a positive HPV test; the subjects will be followed-up for 5 years, period from which 3 years have already elapsed, with yearly studies (colposcopy, cytology, and histopathology diagnosis, along with molecular HPV test, quantification of viral load and of IL-10, IL-4, TGFβ1, INFγ, IL-6, and TNFα levels, along with the expression of the HR-HPV E6/E7 proteins in the cervix as a viral marker. The outcome will be categorized as viral persistence or clearance; and as SIL persistence, progression, or regression. Binomial and/or multinomial regression models adjusted for potential confounders will be used, associating the relative risk of the outcome with the immune and viral markers evaluated.
This research will generate knowledge about immune markers with predictive value for the persistence and clearance of HPV, which will improve the triage of positive HPV women and thus reduce the economic burden for the Mexican health system imposed by the management of high-grade SIL and CC cases, which are still detected in late stages.
宫颈癌（CC）是由高危型人乳头瘤病毒（HR-HPV）持续感染引起的。虽然大多数 HPV 感染是短暂的，但持续性 HPV 感染是墨西哥的一个重大健康问题。在生育年龄的女性中，HPV 感染率估计为 10%，其中约 25%的女性在初筛试验中至少出现阳性结果，根据之前的研究，这些结果预计将被确认为阳性 CIN-2/3。免疫系统在 HPV 感染的自然史中起着关键作用；细胞免疫反应的改变导致 HPV 无法被清除。本项目的目的是评估检测免疫标志物（IL-10、IL-4、TGFβ1、IFNγ、IL-6 和 TNFα）、HPV-HR E6/E7 蛋白的表达以及宫颈水平的病毒载量与 HR-HPV 感染的持续性或清除、宫颈前病变的消退或进展的预后价值。
正在对宫颈阴道镜检查、细胞学和组织病理学结果为鳞状上皮内病变（SIL）阴性且 HPV 检测阳性的女性进行动态队列研究；这些女性将被随访 5 年，目前已经过去了 3 年，每年进行研究（阴道镜检查、细胞学和组织病理学诊断，以及分子 HPV 检测、病毒载量和 IL-10、IL-4、TGFβ1、IFNγ、IL-6 和 TNFα 水平的定量检测，以及宫颈 HR-HPV E6/E7 蛋白的表达作为病毒标志物）。结果将分为病毒持续性或清除性；以及 SIL 持续性、进展或消退。将使用调整潜在混杂因素的二项式和/或多项式回归模型，将与结局相关的相对风险与评估的免疫和病毒标志物相关联。
这项研究将产生具有预测价值的免疫标志物，用于 HPV 的持续性和清除性，这将改善 HPV 阳性女性的分流，从而减少墨西哥卫生系统管理高级别 SIL 和 CC 病例的经济负担，这些病例仍在晚期发现。
