Jin Fengyi, Roberts Jennifer M, Grulich Andrew E, Poynten Isobel M, Machalek Dorothy A, Cornall Alyssa, Phillips Samuel, Ekman Deborah, McDonald Ross L, Hillman Richard J, Templeton David J, Farnsworth Annabelle, Garland Suzanne M, Fairley Christopher K, Tabrizi Sepehr N
aThe Kirby Institute, University of New South Wales bDouglass Hanly Moir Pathology, Sydney, New South Wales cRoyal Women's Hospital, University of Melbourne, Murdoch Childrens Research Institute, Melbourne, Victoria dWestern Sydney Sexual Health Centre, University of Sydney eSt Vincent's Hospital, Sydney, New South Wales fRPA Sexual Health, Sydney Local Health District and Central Clinical School, University of Sydney, Sydney, New South Wales gMelbourne Sexual Health Centre, Melbourne, Victoria, Australia.
AIDS. 2017 Jun 1;31(9):1303-1311. doi: 10.1097/QAD.0000000000001462.
We evaluate the performance of human papillomavirus (HPV) biomarkers in prediction of anal histological high-grade squamous intraepithelial lesions in gay and bisexual men (GBM) in Sydney, Australia.
Baseline analysis of a 3-year cohort study.
The Study of the Prevention of Anal Cancer is natural history study of anal HPV infection in GBM aged at least 35 years. All participants completed cytological and histological assessments. Stored ThinPrep PreservCyt residua were tested for HPV genotyping (Linear Array and Cobas 4800) and viral load, E6/E7 mRNA expression (NucliSENS easyQ HPV v1) and dual cytology staining of p16/Ki 67 antibodies (CINtecPLUS). Performance of each biomarker was compared with liquid-based anal cytology. The hypothetical referral rates were defined as the proportion of men who had abnormal cytology or tested positive to each of the biomarkers.
The median age of the 617 participants was 49 years (range: 35-79), and 35.7% were HIV-positive. All biomarkers were strongly associated with the grade of HPV-associated anal lesions (P < 0.001 for all). High-risk HPV (HR-HPV) viral load with a 33% cut-off and HR-HPV E6/E7 mRNA had similar sensitivity to anal cytology (78.4 and 75.4 vs. 83.2%, respectively), improved specificity (68.0 and 69.4 vs. 52.4%, respectively) and lower referral rates (47.0 and 45.0 vs. 59.2%, respectively). Specificity was significantly higher in the HIV-negative for HR-HPV viral load (72.3 vs. 58.2%, P = 0.005).
HR-HPV viral load and E6/E7 mRNA had similar sensitivity and higher specificity in predicting histological anal high-grade squamous intraepithelial lesion with lower referrals in GBM than anal cytology.
我们评估了人乳头瘤病毒(HPV)生物标志物在预测澳大利亚悉尼男同性恋者和双性恋男性(GBM)肛门组织学高级别鳞状上皮内病变方面的性能。
一项为期3年的队列研究的基线分析。
预防肛门癌研究是一项针对年龄至少35岁的GBM人群肛门HPV感染自然史的研究。所有参与者均完成了细胞学和组织学评估。对储存的ThinPrep PreservCyt残余物进行HPV基因分型检测(线性阵列和Cobas 4800)以及病毒载量、E6/E7 mRNA表达检测(NucliSENS easyQ HPV v1)和p16/Ki 67抗体的双重细胞学染色检测(CINtecPLUS)。将每个生物标志物的性能与液基肛门细胞学进行比较。假设转诊率定义为细胞学异常或各生物标志物检测呈阳性的男性比例。
617名参与者的中位年龄为49岁(范围:35 - 79岁),35.7%为HIV阳性。所有生物标志物均与HPV相关肛门病变的分级密切相关(所有P值均<0.001)。以33%为临界值的高危HPV(HR-HPV)病毒载量和HR-HPV E6/E7 mRNA与肛门细胞学具有相似的敏感性(分别为78.4%和75.4%,而肛门细胞学为83.2%),特异性有所提高(分别为68.0%和69.4%,而肛门细胞学为52.4%),转诊率更低(分别为47.0%和45.0%,而肛门细胞学为59.2%)。HR-HPV病毒载量在HIV阴性者中的特异性显著更高(72.3%对58.2%,P = 0.005)。
在预测GBM人群的组织学肛门高级别鳞状上皮内病变方面,HR-HPV病毒载量和E6/E7 mRNA具有相似的敏感性和更高的特异性,与肛门细胞学相比转诊率更低。