Wieland Ulrike, Hellmich Martin, Wetendorf Janna, Potthoff Anja, Höfler Daniela, Swoboda Jochen, Fuchs Wolfgang, Brockmeyer Norbert, Pfister Herbert, Kreuter Alexander
National Reference Center for Papilloma- and Polyomaviruses, Institute of Virology, Uniklinik Köln, University of Cologne, Fuerst-Pueckler-Str. 56, 50935 Koeln, Germany.
Institute of Medical Statistics, Informatics and Epidemiology, University of Cologne, Kerpener Str. 62, 50924 Koeln, Germany.
Int J Med Microbiol. 2015 Oct;305(7):689-96. doi: 10.1016/j.ijmm.2015.08.019. Epub 2015 Aug 21.
HIV-positive men who have sex with men (MSM) have an increased risk for anal human papillomavirus (HPV) infection, anal high-grade intraepithelial lesions (HSIL), and anal cancer. Smoking is associated with abnormal anal cytology and with an increased risk for anal cancer. We collected 3736 intraanal swabs from 803 HIV-positive MSM who participated in an anal cancer screening program between October 2003 and August 2014. HPV prevalence, anal cytology and HPV DNA load of high-risk (HR) HPV-types 16, 18, 31 and 33 of non-smokers and smokers were compared. HPV-typing was performed by alpha-HPV genus-specific PCR and hybridization with 38 type-specific probes using a multiplex genotyping assay. In samples positive for HPV16, 18, 31, or 33, HPV DNA loads were determined by type-specific real-time PCRs and expressed as HPV DNA copies per betaglobin gene copy. At baseline, HR-HPV DNA (80.5 vs. 89.0%, p=0.001), HPV16 DNA (41.6 vs. 52.3%, p=0.003), HPV18 DNA (15.5 vs. 26.0%, p<0.001), anal dysplasia (LSIL+HSIL; 51.5 vs. 58.4%, p=0.045) and HSIL (17.2 vs. 22.7%, p=0.048) were detected more frequently in smokers compared to non-smokers. Throughout the study period 32.7% of non-smokers and 39.9% of smokers developed HSIL (p=0.011), and three smokers developed anal cancer. Considering swabs from the entire study period (median HPV load value per patient per cytology grade), smokers with normal anal cytology had significantly higher HPV16 loads (median 0.29 vs. 0.87, n=201, p=0.007) and cumulative high-risk-HPV loads (median 0.53 vs. 1.08, n=297, p=0.004) than non-smokers. Since elevated HR-HPV DNA loads are associated with an increased risk for HPV-induced anogenital cancers, HPV-infected HIV-positive MSM should be counseled to refrain from smoking. Additionally, for smokers, shorter anal cancer screening intervals than for non-smokers may be appropriate.
与男性发生性关系的艾滋病毒阳性男性（男男性行为者）感染肛门人乳头瘤病毒（HPV）、发生肛门高级别上皮内瘤变（HSIL）和患肛门癌的风险增加。吸烟与肛门细胞学异常及患肛门癌风险增加有关。我们从803名参与2003年10月至2014年8月肛门癌筛查项目的艾滋病毒阳性男男性行为者中收集了3736份肛门拭子。比较了非吸烟者和吸烟者的HPV感染率、肛门细胞学及高危（HR）HPV-16、18、31和33型的HPV DNA载量。通过α-HPV属特异性PCR及使用多重基因分型检测与38种型特异性探针杂交进行HPV分型。在HPV16、18、31或33阳性的样本中，通过型特异性实时PCR测定HPV DNA载量，并以每β球蛋白基因拷贝的HPV DNA拷贝数表示。基线时，与非吸烟者相比，吸烟者中HR-HPV DNA（80.5%对89.0%，p=0.001）、HPV16 DNA（41.6%对52.3%，p=0.003）、HPV18 DNA（15.5%对26.0%，p<0.001）、肛门发育异常（低度鳞状上皮内病变+高度鳞状上皮内病变；51.5%对58.4%，p=0.045）及HSIL（17.2%对22.7%，p=0.048）的检出频率更高。在整个研究期间，32.7%的非吸烟者和39.9%的吸烟者发生了HSIL（p=0.011），3名吸烟者患了肛门癌。考虑整个研究期间的拭子（每位患者每个细胞学分级的HPV载量中位数），肛门细胞学正常的吸烟者的HPV16载量（中位数0.29对0.87，n=201，p=0.007）和累积高危HPV载量（中位数0.53对1.08，n=297，p=0.004）显著高于非吸烟者。由于HR-HPV DNA载量升高与HPV诱导的肛门生殖器癌症风险增加有关，应建议感染HPV的艾滋病毒阳性男男性行为者戒烟。此外，对于吸烟者，与非吸烟者相比，缩短肛门癌筛查间隔可能是合适的。
