Objective: To determine the morbidity of cervical intraepithelial neoplasia 2+ (CIN2+ ) and CIN3+ of different human papillomavirus(HPV) subtype infection combined with different cytology status. Methods: The Shenzhen Cervical Cancer Screening Trial Ⅰ & Ⅱ (SHENCCASTⅠ&Ⅱ) are population-based cross-sectional cervical cancer screening studis conducted in Shenzhen and surrounding area from 2008 to 2010. A total of 12 097 women who aged 25-59 years were included in the analysis. All of these women were detected by liquid-based cytology test and several high-risk HPV-DNA tests. The ones with HPV positive or atypical squamous cells of undetermined sign (ASC-US) were sequentially conducted by cervical biopsy vaginoscopy. Finally, 10 805 samples with complete data of hybrid capture 2(HC2), the polymerase chain reaction-based matrix-assisted laser desorption/ionization time-of-flight assay (MALDI-TOF), HPV genotyping detection, cytology and pathology results were analyzed. Results: The top 6 infection rates of HR-HPV in CIN2+ and CIN3+ were HPV16, HPV52, HPV58, HPV33, HPV31, HPV18. The highest constituent ratio of cytology in CIN2+ and CIN3+ was high grade squamous intraepithelial lesion(HSIL). The morbidities of CIN2+ of patients infected with HPV16, HPV31, HPV58, HPV33, HPV18, HPV52 were 41.3%, 31.5%, 30.6%, 28.7%, 28.2%, 17.7%, respectively, while the morbidities of CIN3+ of those were 33.5%, 20.5%, 19.4%, 15.7%, 19.2%, 8.3%, respectively.The morbidities of CIN2+ in negative intraepithelial lesion or malignancy (NILM), ASC-US, low grade squamous intraepithelial lesion (LSIL), atypical squamous cell cannot exclude high-grade squamous intraepithelial lesion (ASC-H), high grade squamous intraepithelial lesion (HSIL), atypical glandular cell (AGC) samples were 0.4%, 6.9%, 11.1%, 36.4%, 82.0%, 16.7%, respectively, while the morbidities of CIN3+ of those were 0.2%, 3.1%, 4.2%, 22.7%, 64.8%, 0.0%, respectively. The morbidities of CIN2+ in NILM combined with HPV16, HPV18, HPV31, HPV33 infection were 12.6%, 13.3%, 15.8% and 11.5%, respectively, while the morbidities of CIN3+ of those were 10.3%, 11.1%, 7.9% and 7.7%, respectively.The morbidities of CIN2+ and CIN3+ in ASC-US combining with hrHPV infection were high, and the top 6 subtypes associated with high risk of CIN2+ were HPV31 (35.7%), HPV33 (26.9%), HPV16 (26.5%), HPV58 (22.4%), HPV52 (18.6%), HPV68 (15.4%), while those associated with high risk of CIN3+ were HPV16 (20.4%), HPV31 (14.3%), HPV33 (11.5%), HPV58 (8.6%), HPV68 (7.7%), HPV52 (5.8%). Conclusions: Cytology combined with HPV genotyping detection can more effectively estimate the morbidity risks of CIN2+ and CIN3+ . Both high prevalence rates and high risks associated with CIN2+ and CIN3+ of HPV31, HPV33, HPV52 and HPV58 are observed. NILM and ASC-US status combined with these subtypes mentioned above are advised to be conducted by colposcopy.
目的： 研究不同亚型人乳头状瘤病毒(HPV)感染合并宫颈细胞学异常状态者宫颈鳞状上皮内瘤样病变2级及以上(CIN2＋)或3级及以上(CIN3＋)的患病情况。 方法： 2008—2010年在深圳和周边地区开展的两项以人群为基础的宫颈癌筛查横断面研究，共12 097名25～59岁的妇女参加。通过液基细胞学联合多种高危型人乳头瘤病毒(hrHPV)检测方法进行筛查，对细胞学结果为意义不明的不典型鳞状上皮细胞(ASC－US)及以上者或任一种HPV检测结果阳性者行阴道镜下宫颈组织活检。最终10 805名具有完整第二代杂交捕获技术(HC2)、基质辅助激光解吸电离飞行时间质谱(MALDI) HPV分型检测结果及细胞学、病理结果的妇女纳入分析。 结果： CIN2＋和CIN3＋中，HPV感染率前6位的亚型为HPV16、HPV52、HPV58、HPV33、HPV31和HPV18。CIN2＋和CIN3＋中细胞学构成比最高的为高度鳞状上皮内病变(HSIL)。感染HPV16、HPV31、HPV58、HPV33、HPV18、HPV52者CIN2＋的发生率分别为41.3%、31.5%、30.6%、28.7%、28.2%和17.7%，CIN3＋的发生率分别为33.5%、20.5%、19.4%、15.7%、19.2%和8.3%；无宫颈上皮病变或恶性细胞(NILM)、ASC－US、低度鳞状上皮内病变(LSIL)、非典型鳞状上皮－不除外高度病变(ASC－H)、HSIL、非典型腺上皮细胞(AGC)人群中，其CIN2＋的发生率分别为0.4%、6.9%、11.1%、36.4%、82.0%和16.7%；CIN3＋的发生率分别为0.2%、3.1%、4.2%、22.7%、64.8%和0.0%。NILM合并HPV16、HPV18、HPV31、HPV33 4种亚型感染人群CIN2＋的发生率分别为12.6%、13.3%、15.8%和11.5%；CIN3＋的发生率分别为10.3%、11.1%、7.9%和7.7%。ASC－US合并各hrHPV感染的人群中，其CIN2＋发病率前6位为HPV31(35.7%)、HPV33(26.9%)、HPV16(26.5%)、HPV58(22.4%)、HPV52(18.6%)和HPV68(15.4%)；CIN3＋发病率前6位为HPV16(20.4%)、HPV31(14.3%)、HPV33(11.5%)、HPV58(8.6%)、HPV68(7.7%)和HPV52(5.8%)。 结论： 细胞学联合HPV亚型分析能更有效地评估CIN2＋和CIN3＋的患病风险；HPV31、HPV33、HPV52和HPV58的流行率高，在合并NILM与ASC－US状态时，患CIN2＋和CIN3＋的风险大，或有必要行阴道镜检查。.
Keywords: Cervical intraepithelial neoplasia; Human papillomavirus; Liquid based cytology; Matrix-assisted laser desorption/ionization time-of-flight.