Cytology vs at home HPV screening for detection of CIN 2,3,CIS

描述（由申请人提供）：我们建议在接种过/未接种过HPV 16/18疫苗的女性中进行一项随机临床试验，以比较目前推荐的基于细胞学的筛查方法和一种新的方法筛查CIN 2- 3/CIS的敏感性、特异性、成本效益和可接受性，这种新方法是对自我收集的样本进行高风险(HR)-HPV DNA检测，然后进行临床细胞学检查，以便HR- HPV阳性女性进行阴道镜检查。我们还将探讨通过HPV基因分型和/或检测表观遗传变化对HR-HPV阳性妇女进行分类的潜在效用。拟议研究的意义在于，尽管有预防性HPV 16/18疫苗，筛查仍需继续，尽管在没有疫苗的情况下，基于细胞学的筛查非常有效，但成本效益分析表明，在基于细胞学的筛查中增加疫苗接种的增量成本效益比将远远超过通常引用的支付意愿阈值。此外，在接种HPV疫苗的妇女中，细胞学的PPV将降低。其他国家的研究表明，基于HPV的筛查基于细胞学的分诊将比基于细胞学的筛查更敏感和特异性，即使在接种了HR-HPV疫苗的妇女中也是如此。这项研究是新颖的，因为用细胞学分类进行HPV筛查与疫苗接种的关系尚未得到检验，或与家庭标本收集相结合。此外，基于细胞学分类的HPV筛查尚未在美国人群中进行过检查，与以往不同的是，我们将确定每种方法的绝对灵敏度和特异性，而不是相对灵敏度和特异性，并根据从研究参与者完成筛查后立即收集的数据进行成本效益分析。证明这种新方法的效用的潜在影响是，最终广泛采用一种更符合HPV疫苗时代的更具成本效益的CCC方法。Kiviat博士、Kulasingam博士、Hawes博士、Feng博士和Emerson博士在成功开展大型临床试验和成本效益分析方面有着良好的记录，这些试验和分析挑战/改变了CCC的临床实践范式。

DESCRIPTION (provided by applicant): We propose to conduct a randomized clinical trial among women who have/have not been vaccinated against HPV 16/18, to compare the sensitivity, specificity, cost-effectiveness and acceptability of screening for CIN 2- 3/CIS using the currently recommended cytology-based screening approach and a novel approach in which self collected samples are tested for high risk (HR)-HPV DNA followed by in-clinic cytology for triage of HR- HPV positive women to colposcopy. We will also explore the potential utility of triage of HR-HPV positive women by HPV genotyping and/or detection of epigenetic changes. The significance of the proposed study is that despite the availability of prophylactic HPV 16/18 vaccines, screening will need to continue and although, in the absence of a vaccine, cytology based screening was highly effective, cost-effectiveness analyses suggest that the incremental cost-effectiveness ratio of adding vaccination to cytology-based screening will far exceed commonly-cited willingness to pay thresholds. Further, the PPV of cytology will be decreased among HPV vaccinated women. Studies in other countries suggest that HPV based screening the cytology based triage will be more sensitive and specific than cytology based screening even among women vaccinated against HR-HPV. The study is novel as HPV screening with cytology triage has not been examined in relationship to vaccination, or in combination with home based collection of specimens. Further, HPV based screening with cytology triage has not yet been examined in US based populations, and, unlike previous, we will determine the absolute, rather than the relative, sensitivity and specificity of each approach, and carry out cost effectiveness analyses based on data collected from study participants immediately after they complete screening. The potential impact of demonstrating the utility of this novel approach is the eventual widespread adoption of a more cost effective approach to CCC, appropriate to the era of HPV vaccines. Dr. Kiviat, Kulasingam, Hawes, Feng and Emerson have proven track records for successfully carrying out large, clinical trials and cost-effectiveness analyses which have challenged/changed clinical practice paradigms of CCC. PUBLIC HEALTH RELEVANCE: Developing novel sensitive, specific and cost effective approaches to cervical cancer control (CCC) for women who have/have not received the HPV vaccine is of great public health importance. This study will compare our current Pap smear based screening approach for cervical cancer control, to cervical cancer control using home based HPV screening assays. This novel approach would more cost effective than currently recommended approaches.