各亚类AGC患者的HPV感染情况与组织学结果随访研究

Prevalence,Genotype Distribution of the High Risk Human Papillomavirus and Histological Follow-up in Women with Various Subcategorys Atypical Glandular Cells

目的分析各亚类非典型腺细胞(atypical glandular cell,AGC)患者的高危亚型人乳头瘤病毒(high risk human papillomavirus,hrHPV)感染率、基因分型情况、与组织学结果的相关性,以明确AGC诊断的临床意义,并探讨hrHPV检测在腺上皮病变筛查及分流管理中的意义。方法对中国人民解放军空军军医大学第一附属医院2017~2019年细胞学筛查为AGC的病例进一步进行HPV-DNA分型检测及组织病理学随访。结果247例AGC中,取得组织学结果205例,结果为不典型增生及以上者101例(49.3%),包括50例(24.4%)鳞状上皮病变,25例(12.2%)原位腺癌/腺癌,21例(10.2%)子宫内膜复杂型增生伴不典型/内膜癌,5例(2.5%)其他肿瘤。AGC细胞学各亚类中,非典型子宫内膜细胞组随访阳性率为51.9%,其中子宫内膜病变占78.6%,而非典型子宫颈管细胞组随访阳性病例中,子宫颈病变占88.9%。247例AGC中,取得HPV-DNA检测结果的200例,其中hrHPV阳性的86例(43.0%)。hrHPV阳性病例随访HSIL以上严重病变的发生率明显高于hrHPV阴性病例,风险比为5.1(95%CI:2.7~9.7,P<0.001)。阳性率最高的依次是16和18亚型,合计占比超过一半(62.7%)。排除鳞状上皮病变的干扰因素后,阳性率最高的仍然为16和18亚型,且合计占比提高到80.8%。结论AGC虽然诊断率低,但往往与严重的组织学病变相关。细胞学进一步细分AGC亚类,对于确定病变发生位置及后续检查和治疗有重要指导意义。hrHPV阳性的患者,尤其是16、18亚型阳性的AGC患者,发生高级别鳞状上皮内病变(high-grade squamous intraepithelial lesion,HSIL)及以上严重病变的潜在风险更高,而对于hrHPV阴性的AGC患者应当重点排除宫腔及子宫外肿瘤。

Objective To explore the hrHPV infection rate,distribution of hrHPV genotypes and histological follow-up of patients with various subcategorys of AGC,so as to clarify the clinical significance of AGC diagnosis,and evaluate the significance of hrHPV detection for managing women with atypical glandular cells.Methods HPV-DNA typing and histological follow-up were further performed on patients diagnosed with AGC by cytological screening in our hospital from 2017 to 2019.Results Of 247 AGC cases,205 cases had histological follow-up results within 1 year,including 101 cases(49.3%)of hyperplasia or above,which contains 50 cases of squamous lesion(24.4%),25 cases of adenocarcinoma in situ(AIS)/adenocarcinoma(12.2%),21 cases of complex atypical hyperplasia(CAH)/endometrial carcinoma(10.2%),and 5 cases of other tumors(2.5%).Among the AGC subcategorys,the positive rate of atypical endometrial cells(AMC)was 51.9%,of which endometrial lesions accounted for 78.6%,while cervical lesions accounted for 88.9%in atypical endocervical cells.Of the 247 AGC patients,200 obtained HPV-DNA test results,86(43.0%)hrHPV-positive patients had significantly higher incidence of significant lesions(HSIL+)than hrHPV-negative patients,with odds ratio of 5.1(95%CI:2.7-9.7,P<0.001).We found that HPV16 and 18 were the most commonly detected hrHPV subtypes in AGC cases,accounting for more than half(62.7%).After excluding the interference factors of squamous epithelial lesions,HPV16 and 18 still were the most common hrHPV subtypes,and the total proportion was further increased to 80.8%.Conclusion Although the diagnostic rate of AGC is low,it is often associated with significant lesions.Further subcategorization of AGC would be beneficial in estimating the lesion site,subsequent examination and treatment.A positive hrHPV result,especially HPV16 or 18,is associated with an increased risk of developing significant lesions,while patients with hrHPV-negative AGC should focus on excluding endometrium and extrauterine tumors.