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细胞学、组织P16INK4A和HPV感染结果与年轻妇女CIN1进展情况的相关性研究

Correlation of cytology, tissue P16INK4A and HPV infection outcomes with CIN1 progression in young women

    摘要
  • 摘要:
    目的 探索在不同细胞学筛查结果、免疫组化染色法体现抑癌基因P16INK4A表达情况和人乳头瘤病毒（human papilloma virus，HPV）感染状态下，轻度宫颈上皮内瘤样病变（cervical intraepithelial neoplasia grade Ⅰ，CIN1）人群的进展状况。
    方法 回顾性分析2008 — 2019年149例初次宫颈活检病理为CIN1的年轻妇女的长期随访资料，以中重度宫颈上皮内瘤样病变（CIN2+）为研究终点，使用Kaplan-Meier生存分析计算CIN2+的累积发生率和平均生存时间，使用Log Rank检验比较不同检测结果组间的生存时间差异性，使用Cox回归计算细胞学筛查结果、组织P16INK4A表达情况和HPV感染状态对进展为CIN2+的风险比。
    结果 149例CIN1人群的中位随访时间为68个月，随访结束时共有16例进展为CIN2+，CIN2+的累积发生率为10.74%。细胞学不除外高级别鳞状上皮内病变/高度鳞状上皮内病变/非典型性腺细胞的妇女进展风险是细胞学阴性/意义不明确的非典型鳞状细胞/低度鳞状上皮内病变妇女的3.04倍（95% CI：1.06 ~ 8.76，P = 0.04）。组织P16INK4A弥漫性染色阳性妇女CIN2+的累积发生率为14.00%，进展风险是P16INK4A弥漫性染色阴性者的1.70倍（95% CI：0.63 ~ 4.58，P = 0.29）。HPV-16/18感染、HPV-31/33/45/52/58感染和其他HPV高危型别感染妇女CIN2+的累积发生率分别为34.78%、9.84%和2.63%，进展风险分别是高危HPV阴性者的12.70倍（95% CI：1.58 ~ 102.16，P = 0.02）、2.96倍（95% CI：0.36 ~ 24.60，P = 0.32）和0.82倍（95% CI：0.05 ~ 13.05，P = 0.89）。联合分析HPV感染状态和组织P16INK4A染色结果时发现，HPV-16/18感染且P16INK4A弥漫性阳性人群进展为CIN2+的风险是高危HPV感染和P16INK4A弥漫性染色同时阴性人群的14.43倍（95% CI：1.60 ~ 130.49，P = 0.02）。
    结论 细胞学筛查结果和HPV-16/18检测对CIN1的进展具有重要指示作用，而组织P16INK4A染色作为CIN1进展参考指标的可行性还需进一步研究。

     

    Abstract:
    Objective To explore the progression of cervical intraepithelial neoplasia grade Ⅰ (CIN1) in a population with different cytological results, oncogene P16INK4A expression reflected by immunohistochemical staining, and human papilloma virus (HPV) infection status.
    Methods The long-term follow-up data of 149 young patients with CIN1 confirmed by initial cervical pathological biopsy from 2008 to 2019 were retrospectively analyzed. Using CIN2+ as the study endpoint, cumulative incidence and mean survival time of CIN2+ were calculated by Kaplan-Meier survival analysis, variability in survival time between groups with different test results were compared by the Log Rank test, and risk ratios of cytologic screening results, tissue P16INK4A expression, and HPV infection status for progression to CIN2+ were calculated by Cox regression.
    Results The median follow-up period of the 149 CIN1 cases was 68 months, with a total of 16 progressed to CIN2+ at the end of follow-up, and the cumulative incidence of CIN2+ was 10.74%. The risk of progression in women with atypical squamous cells, cannot exclude high-grade squamous inteaepithel-ial lesion (ASC-H)/highgrade squamous intraepithelial lesion (HSIL)/atypical glandular cells(AGC) was 3.04 times (95% CI: 1.06 − 8.76, P = 0.04) higher than that in women with atypical squamous cells of undetermined significance(ASC-US)/low grade squamous intraepithelial lesion (LSIL) (95% CI: 1.06 − 8.76, P = 0.04). The cumulative incidence of CIN2+ in women with positive tissue P16INK4A diffuse staining was 14.00%, and its progression was 1.70 times (95% CI: 0.63 − 4.58, P = 0.29) higher than that of women with negative P16INK4A diffuse staining. The cumulative incidence of CIN2+ in women with HPV-16/18 infections, HPV-31/33/45/52/58 infections, and infections with other high-risk HPV types were 34.78%, 9.84%, and 2.63%, respectively, with a risk of progression being 12.70 (95%CI: 1.58 − 102.16, P = 0.02), 2.96 (95% CI: 0.36 − 24.60, P = 0.32) and 0.82(95% CI: 0.05 − 13.05, P = 0.89) times higher than that of high-risk HPV negative women.When HPV infection status and tissue P16INK4A staining results were jointly analyzed, it was found that the risk of progression to CIN2+ among women with HPV-16/18 infection and positive concomitant P16INK4A diffuse staining was 14.43 times (95% CI: 1.60 − 130.49, P = 0.02) higher than that of women with high-risk HPV infection and negative concomitant P16INK4A diffuse staining simultaneously.
    Conclusion Cytological screening results and HPV-16/18 testing are closely associated with CIN1 progression, while the feasibility of tissue P16INK4A staining as a reference indicator for CIN1 progression needs further to be studied.

     

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