Improving screening tools to better predict high-grade anal dysplasia for MSM

改进筛查工具以更好地预测 MSM 的重度肛门发育不良

• 批准号: 8506413
• 负责人: DOROTHY J. WILEY
• 金额: $ 60.4万
• 依托单位: UNIVERSITY OF CALIFORNIA LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-09-05 至 2018-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8506413
• 关键词: Affect; Algorithms; Anus; Attention; Atypia; Atypical Squamous Cell; Biological Assay; Biological Markers; Biopsy; Bisexual; Cellularity; Cervical; Cervical dysplasia; Characteristics; Clinical; Collection; Colposcopy; Consensus; Cytology; DNA; Data; Detection; Diagnostic; Diagnostic tests; Dysplasia; FDA approved; Female; Gays; Genital system; Genotype; Globin; HIV; HIV Infections; HPV-High Risk; Health; High Prevalence; Human Papillomavirus; Hybrids; In Situ; Incidence; Individual; Infection; Laboratories; Life; Malignant Neoplasms; Malignant neoplasm of anus; Malignant neoplasm of cervix uteri; Measures; Messenger RNA; Molecular; Morbidity - disease rate; Nucleic Acids; Nylons; Pap smear; Predictive Value; Procedures; Proteins; Protocols documentation; Quality of life; Quality-Adjusted Life Years; RNA; Randomized Controlled Clinical Trials; Randomized Controlled Trials; Relative (related person); Research; Research Design; Risk; Savings; Sensitivity and Specificity; Series; Sexually Transmitted Diseases; Signal Transduction; Specificity; Specimen; Staining method; Stains; Swab; Testing; Translations; Triage; Visit; Woman; antiretroviral therapy; cost; cost effective; cost effectiveness; dacron; disorder risk; follow-up; high risk; human DNA; human papilloma virus oncogene; improved; instrumentation; life time cost; male; men; men who have sex with men; mortality; performance tests; prevent; public health relevance; sample collection; screening; sex; tool; transgender; viral DNA

DESCRIPTION (provided by applicant): Invasive anal cancer (IAC) is a health crisis for gay, bisexual, transgender & other men who have sex with men (MSM), where risk for disease is now 20-40-fold higher than all U.S. males.9-12 Thirteen human papillomaviruses (high-risk HPVs) cause most invasive cervical cancers (ICC) in women & likely cause most IACs.13 High-risk HPV infections are sexually transmitted between partners. Persistent infections, together with their associated high-grade dysplasias, strongly predict ICCs.14-17 Recent data suggests we poorly understand HPV infections in men, especially among MSM who are at highest risk for IAC.18-25 Cervical cytology using Papanicolaou's staining (Pap test) significantly reduced ICC beginning in the mid-1950's; & cytology specimens are currently collected using cytobrush, a tool poorly adapted to anal sampling.26,27 Experts now recommend anal Pap test for MSM every 1-2 years, using Dacron swab passed blindly through the anal verge.28 Dacron-cytology specimens are marginally sufficient & require diagnostic follow-up for any detected abnormalities, a lower threshold than used for cervical cytology. Our pilot data show that sensitivity & specificity of anal cytology to predict HG-AIN is improved 1.5-fold using nylon-flocked swab, but only improved specificity 1.3-fold to 73%. Although most IACs test positive for HPV using PCR, the high prevalence of infection among MSM without cancer makes HPV PCR genotyping a poorly specific screening test, with low positive predictive value (PPV). High-threshold, nucleic acid HPV assays (molecular HPV tests) are calibrated to better predict high-grade cervical dysplasia in older females without atypias & to triage women to colposcopy with atypical squamous cells on cytology; they are not calibrated for IAC screening. Two molecular HPV tests that detect viral DNA & -mRNA may be relevant for IAC screening: HPV-Hybrid-capture II (HC-2) & -APTIMA. Both tests detect the 13 highest-risk HPVs; APTIMA detects HPV66, additionally. HC-2 detects HPV-DNA >1 pg/mL.29 HPV E6/E7 are often detected at higher levels where HPV is integrated into human DNA, a hallmark of cancer.30 Molecular HPV tests significantly reduce diagnostic follow-up referrals for women with equivocal cytology, limiting costly & invasive procedures, & while these tests improve detection of in situ & ICCs, they have not been explored as adjunctive tests for IAC screening. Also, sufficient attention has not been paid to improving the quality of anal Pap test specimens. This study seeks to evaluate two Pap test collection protocols & molecular HPV tests, as biomarker assays, using specimens collected at a single examination visit & randomized controlled study design. Optimizing the sequence of biomarker assays & cytology to predict HG- AIN will decrease morbidity & mortality, & lower use of costly & invasive diagnostic testing. We will evaluate the contribution that molecular HPV testing makes when simultaneously or sequentially positive tests, with or without (anal) cytology, are used to predict HG-AIN. Sensitivity, specificity, & PPV for anal cancer screening algorithms & their cost-effectiveness to prevent invasive anal cancer will be evaluated to inform practice.

DESCRIPTION (provided by applicant): Invasive anal cancer (IAC) is a health crisis for gay, bisexual, transgender & other men who have sex with men (MSM), where risk for disease is now 20-40-fold higher than all U.S. males.9-12 Thirteen human papillomaviruses (high-risk HPVs) cause most invasive cervical cancers (ICC) in women & likely cause most IACs.13 High-risk HPV感染是在伴侣之间进行性传播的。持续性感染及其相关的高级发育不良，强烈预测ICC.14-17最近的数据表明，我们对男性的HPV感染很糟糕，尤其是在MSM中，他们使用Papanicolaou的静止ICC（PAP TEST）的IAC最高风险。目前，使用细胞刷（该工具）对肛门采样的适应不良。26,27专家现在建议每1 - 2年的MSM进行肛门PAP测试，使用DACRON SWAB盲目通过肛门Verge进行。28DACRON-CYTEGOL学标本略有足够的诊断来进行任何检测到的Abnortal，并需要适用于Abnortal，＆细胞学标本的适用性较低。我们的试点数据表明，使用尼龙锁的拭子，肛门细胞学对预测HG-AIN的敏感性和特异性提高了1.5倍，但仅提高了特异性1.3倍至73％。尽管大多数IACS使用PCR测试HPV呈阳性，但没有癌症的MSM感染的高流行率使HPV PCR基因分型成为特异性较差的筛选测试，阳性预测值低（PPV）。高阈值，核酸HPV测定法（分子HPV测试）进行校准，以更好地预测没有异型的老年女性中的高级宫颈肿瘤，并将妇女分类为与细胞的非典型鳞状细胞在细胞学上进行分类；它们没有进行校准以进行IAC筛查。检测病毒DNA＆-MRNA的两个分子HPV测试可能与IAC筛查有关：HPV杂交抗体II（HC-2）和-aptima。两种测试都检测到13个最高风险的HPV； APTIMA还检测到HPV66。 HC-2检测HPV-DNA> 1 pg/ml.29 HPV E6/E7通常在较高水平上检测到HPV整合到人DNA中。30分子HPV测试显着降低了诊断的诊断随访，对具有等效性和ICC的女性进行了识别，并在这些测试中进行了识别和ICCECT，并在这些测试中进行了识别和ICCTS，并提高了这些测试，并提高了ICCECT，并提高了ICCECTS，并提高了ICCECTS的测试，并在探索中进行了研究。作为IAC筛查的辅助测试探讨。同样，尚未给予足够的关注以提高肛门子Pap测试标本的质量。这项研究旨在使用在一次检查访问和随机对照研究设计中收集的标本来评估两种PAP测试协议和分子HPV测试，作为生物标志物测定。优化生物标志物测定和细胞学的顺序以预测HG-AIN将降低发病率和死亡率，并降低使用昂贵和侵入性诊断测试的使用。我们将评估分子HPV测试同时或依次呈阳性测试（有或没有（肛门）细胞学）来预测Hg-aIN的贡献。将评估用于肛门癌筛查算法的敏感性，特异性和PPV及其预防侵入性肛门癌的成本效益以告知实践。