【作者】 张东妍；

【导师】 陈祥生；

【作者基本信息】 北京协和医学院 ， 皮肤病与性病学， 2014， 博士

【摘要】 背景大约85%的肛门癌由可致癌的高危基因型HPV感染引起,虽然该病在普通人群中发病率较低(1.5/100,000),但近年的研究已经显示该病的发病率在逐年增加。肛门癌在男男性接触人群(men who have sex with men, MSM)中发病率最高(35/100,000),类似于在宫颈常规细胞学筛查实施之前宫颈癌的发病率。在HIV阳性的MSM人群中,肛门癌的发病率更高(60-70/100,000)。该人群特殊的性行为方式(肛交)及类似宫颈的肛管组织学特点(存在鳞状细胞与柱状细胞交界处)可能与该人群肛门癌发病危险有关。最初的HPV四价及二价疫苗主要针对于在女性中预防宫颈癌设计。2011年10月免疫接种咨询委员会(ACIP)建议将四价HPV疫苗用于男性,特别是MSM人群(包括HIV感染者)。然而,该疫苗是否能够在该人群中有效覆盖可致癌型别的HPV是决定其有效性的重要指标。我国对HPV在MSM人群中的分子流行病学研究较少,仅有的几项研究均是在北方MSM人群中开展,而南方地区的HPV分子流行病学状况如何是有待探讨的课题。本课题首次在位于我国南方地区的深圳市开展MSM人群的HPV分子流行病学研究及危险性行为调查。目的描述中国深圳市MSM人群肛管HPV的流行率及基因型分布,分析该人群肛管HPV感染的可能危险因素。分析深圳市MSM发生商业性行为的可能危险因素。方法2009年7月至9月,通过深圳市为MSM人群提供医疗服务的性病门诊招募MSM。通过一对一问卷调查获取深圳市MSM人群的人口社会学及行为学特征,并采集静脉血进行HIV及梅毒的血清学检测、采集肛拭子进行HPV基因分型和采集尿液进行衣原体及淋球菌的核酸检测。分类资料的单因素分析采用卡方检验。危险因素分析采用单因素及多因素的Logistic回归分析。结果共招募MSM408例,均提供血液、尿液及肛拭子,其中404份肛拭子为有效标本(其余4份中未检测到β球蛋白)。肛管HPV、HIV、梅毒、沙眼衣原体及淋球菌感染阳性率分别为36.4%、6.9%、24.5%、16.2%及7.4%。最常检出的HPV基因型为HPV06(8.2%), HPV16(7.2%), HPV11(6.4%), HPV18(4.7%), HPV58(4.7%)及HPV52(4.2%)。HIV或梅毒阳性MSM的总HPV、致癌性HPV及多重HPV感染的阳性率明显高于阴性MSM。沙眼衣原体感染阳性MSM的总HPV、非致癌性HPV及多重HPV的阳性率明显高于阴性MSM。曾出现过性病相关症状(包括排尿痛或烧灼感、尿道分泌物异常、生殖器或肛门出现皮损或增生物)是总HPV感染(AOR:4.15,95%CI:1.50-11.51, P=0.023)及致癌性HPV感染(AOR:2.88,95%CI:1.16-7.14, P=0.016)的危险因素。30-39年龄组非致癌性HPV的感染率较40岁及以上年龄组低(AOR:0.32,95%CI:0.11-0.91, P=0.033)。与配偶以外的家人同住者单一HPV感染率较独居者低(AOR:0.26,95%CI:0.09-0.77,P=0.015)。近六个月与男性肛交时安全套的使用频率与MSM人群肛管HPV感染无关。HPV感染的危险因素与HIV、梅毒、沙眼衣原体及淋球菌感染的危险因素不同。在143名回答过是否曾发生商业性行为的MSM中有24.5%(35/143)曾发生过商业性行为。近6个月每次与男性肛交均使用安全套者发生商业性行为的比例较高(AOR:3.78,95%CI:1.59-8.98, P=0.003),曾发生过性虐待者进行商业性行为的比例较高(AOR:13.79,95%CI:1.84-160.60, P=0.036)。结论深圳MSM人群肛管HPV感染率较高,HPV6,16,11,18,58及52是最常见的基因型。HIV、梅毒、衣原体阳性及阴性MSM肛管HPV感染率及基因型分布不同。肛管HPV感染的危险因素可能与HIV、梅毒、沙眼衣原体感染的危险因素差异较大。曾发生过性虐待及近6个月每次与男性肛交时均使用安全套的MSM可能较易发生商业性行为。更多还原

【Abstract】 Background Approximately85%of anal cancers worldwide were attributed to the oncogenic HPV. Although anal cancers from HPV infection can afflict both men and women and were rare in the general population (1.5cases/100,000population), men who have sex with men (MSM) were at greatest risk with an incidence of35cases/100,000population, similar to incidence of cervical cancer before implementation of routine cervical screening. The estimated incidence of anal cancer in HIV positive MSM was even greater (60-70cases/100,000population). The special sexual behaviors (anal sex) and the similar histological characteristic of anal canal to the cervix may refer to this phenomenon. Similar to the cervix, a squamo-columnar junction was just between the upper colorectal type mucosa and the lower squamous epithelium in the anal canal. On October25,2011, the Advisory Committee on Immunization Practices (ACIP) had recommended routine use of quadrivalent human papillomavirus (HPV) vaccine (HPV6/11/16/18)in males aged11or12years. Since MSM were at higher risk for infection with HPV types6,11,16, and18and associated conditions, including genital warts and anal cancer, ACIP recommended routine vaccination with HPV4(the quadrivalent HPV vaccine against HPV6,11,16, and18) for all MSM including HIV sero-positive MSM. The high prevalence of oncogenic HPV infection and its association with anal cancer among MSM called for molecular epidemiological studies on anal HPV infection among MSM before the implementation of HPV vaccines in China. In China, rarely studies focused on anal HPV infection in MSM, and the few studies on prevalence of anal HPV infection among MSM were all in northern part of China, while the data on molecular epidemiological studies of anal HPV infection in southern China is limited. The current study firstly described HPV prevalence and genotype distribution in anal canal of MSM in Southern China.Objectives The current study was aimed to describe the prevalence and genotype distribution of HPV in anal canal and estimate the possible risk factors for anal canal HPV infection and commercial sex encounters in MSM in Shenzhen, China.Methods A cross-sectional study was conducted among MSM between July and September of2009in a sexual health clinic providing medical care for MSM in Shenzhen, China. Socio-demographic and sexual behavior data were collected through a face-to-face interview by the trained clinical staff in a separate room using a standardized questionnaire. Blood was collected for HIV serological testing and syphilis serological screening, anal swabs were collected for HPV genotyping, and urine was collected for nucleic acid detection of Chlamydia trachomas (CT) and Neisseria gonorrhoeae (NG). HPV DNA was extracted by QIAamp DNA Mini Kit (Qiagen, Gaithersburg, MD) according to the manufacturer’s instructions. Then HPV DNA was amplified and viral types were determined using the HPV Geno Array test kit (Hybribio, Chaozhou, China) according to the manufacturer’s instructions. Difference of HPV prevalence between HIV, syphilis, chlamydia and gonococcus positive and negative MSM were assessed by chi-square test. Outcome variables included prevalence rates of any type HPV, oncogenic HPV, non-oncogenic HPV, multiple HPV and single HPV infections, et al. Univariate and multivariate Logistic analysis were used to determine association between socio-demographic, behavioral and biomedical characteristics and the infections. The possible risk factors of commercial sex encounters were assessed by chi-square test and unconditional Logistic regression.Results A total of408MSM were consented to provide the blood, anal swabs and urine samples and finished the questionnaires (although not everyone finished all the questions).404of the anal swabs gave valid genotyping results (4/408swabs,0.98%, did not show β-globin amplification). The prevalence of anal HPV, HIV, syphilis, Chlamydia and gonococcus in urine were36.4%,36.4%、6.9%、24.5%、16.2%and7.4%, respectively. The HPV genotypes detected most frequently were HPV06(8.2%), HPV16(7.2%), HPV11(6.4%), HPV18(4.7%), HPV58(4.7%), and HPV52(4.2%). Prevalences of total HPV, oncogenic HPV and multiple HPV infection were significantly higher in HIV or syphilis seropositive MSM than the negatives. Prevalences of total HPV, non-oncogenic HPV and multiple HPV infection were significantly higher in MSM with the infection of Chlamydia than not. Ever had STD (sexually transmitted diseases) associated symptoms (including abnormal secretions, bleeding, breakage, and neoplasia in skin or mucous) was independently associated with detection of any type HPV (AOR:4.15,95%CI:1.50-11.83, P=0.006) and oncogenic HPV (AOR:2.88,95%CI:1.16-7.14, P=0.023) compared to those never had STD associated symptoms. Age between30-39years was independently associated with decreased prevalence of non-oncogenic HPV (AOR:0.32,95%CI:0.11-0.91, P=0.033comparing to40years or plus). Living with families not the spouse was associated with lower prevalence of single HPV in anal canal (AOR:0.26,95%CI:0.09-0.77, P=0.015) compared to those living alone. The frequency of condom using in anal sex with men during the previous6months was not associated with anal HPV infections among MSM in Shenzhen, China. Of143MSM who gave clear answers to whether or not ever had commercial sex encounters,24.5%(35/143) reported ever had commercial sex encounters. Commercial sex encounters were more common in MSM always using condoms in anal sexual behaviors with men in the previous6months (AOR:3.78,95%CI:1.59-8.98, P=0.003comparing to MSM never used condoms in anal sexual behaviors) and MSM ever having sexual maltreat (AOR:13.79,95%CI:1.84-160.60, P=0.036).Conclusions Our study confirms a high burden of anal HPV infection among MSM population in Shenzhen, China. The most popular genotypes were HPV6,16.11,18,58and52. The prevalence and genotype distribution of HPV were different in anal canal of MSM with different HIV, syphilis and Chlamydia infection status. The risk factors for anal canal HPV infection may be different from those for HIV, syphilis and Chlamydia infection. Commercial sex encounters may be more common in MSM ever had sexual maltreat or using condoms in every anal sexual behavior with males in the previous6months.更多还原