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

描述(申请人提供)：我们建议在已接种或未接种HPV16/18疫苗的妇女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。我们还将通过HPV基因分型和/或检测表观遗传学变化来探索对HR-HPV阳性女性进行分类的潜在用途。拟议研究的意义在于，尽管有预防性HPV16/18疫苗可用，但筛查仍需继续，尽管在没有疫苗的情况下，基于细胞学的筛查是非常有效的，但成本效益分析表明，将疫苗接种添加到基于细胞学的筛查中的增量成本效益比将远远超过通常所说的支付阈值的意愿。此外，接种HPV疫苗的妇女细胞学PPV将会降低。其他国家的研究表明，即使在接种了HR-HPV疫苗的妇女中，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。这项研究是新的，因为细胞学分类的HPV筛查尚未与疫苗接种或与家庭样本收集相结合进行检查。此外，基于HPV的筛查和细胞学分类尚未在美国人群中进行检查，与以前不同的是，我们将确定每种方法的绝对而不是相对的敏感性和特异性，并在研究参与者完成筛查后立即根据从他们那里收集的数据进行成本效益分析。展示这一新方法的实用性的潜在影响是最终广泛采用一种更具成本效益的方法来治疗CCC，适合于HPV疫苗时代。Kiviat博士、Kulasingam博士、Hawes博士、冯博士和Emerson博士在成功开展大型临床试验和成本效益分析方面取得了令人信服的记录，这些试验和成本效益分析挑战/改变了CCC的临床实践模式。 公共卫生相关性：为已接种/未接种HPV疫苗的妇女开发新的敏感、特异和成本效益高的宫颈癌控制(CCC)方法对公共卫生具有重要意义。这项研究将比较我们目前基于巴氏涂片的宫颈癌筛查方法和使用家庭HPV筛查分析的宫颈癌控制方法。这一新方法将比目前推荐的方法更具成本效益。

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.