DNA methylation marker for the triage of hrHPV positive women in cervical cancer screening: Real-world evidence in Taiwan.

OBJECTIVE: Human papillomavirus (HPV) testing as the primary cervical cancer screening followed by reflex cytology if high-risk HPV is present (hrHPV+) is recently adopted in some countries. However, reflex cytology's sensitivity is variable, and a suitable triage approach for hrHPV+ remains controversial. Here, we compared the performance of three triage tools in hrHPV+ women. METHODS: Three triage tools-cytology, HPV16/18 genotyping, and DNA methylation biomarker PAX1m-were analyzed for their clinical performance in hrHPV+ women. In addition, women without cervical cancer at enrollment were followed for histologically confirmed high-grade cervical intraepithelial neoplasia or worse (CIN3+) annually using Papanicolaou smear. RESULTS: Of 4762 women aged ≥20 years enrolled, 502 (10.5%) were hrHPV+. PAX1m and cytology demonstrated similar accuracy (>90%), sensitivity (>78%), and specificity (>92%) as triage tools in 429 hrHPV+ women aged 30-64 years. PAX1m had better accuracy and specificity (91.6% and 92.5%, respectively) than HPV16/18 (76.9% and 76.8%, respectively). The incidence of CIN3+ among hrHPV+ women was 10.7 cases/1000 person-years. The incidence was significantly greater in PAX1m-positive women than in PAX1m-negative women. CONCLUSIONS: PAX1m has comparable clinical performance to cytology and better accuracy and specificity than HPV16/18 as the triage tool for detecting CIN3+ in hrHPV+ women. The PAX1m assay is thus a promising molecular-based triage tool for early detection of CIN and predicting disease progression in hrHPV+ women. It can be especially useful in countries where adequate cytology-based infrastructure is lacking, such as some Southeast Asian countries, for cervical cancer screening and prevention.

Definitive intensity-modulated radiation therapy with concurrent chemotherapy for patients with locally advanced cervical cancer.

OBJECTIVE: Cervical cancer is one of the most common cancers diagnosed in women worldwide. Concurrent chemoradiotherapy (CCRT) is the mainstay treatment for locally advanced cervical cancer. The purpose of this study was to investigate the treatment outcomes and toxicity of definitive intensity-modulated radiotherapy (IMRT) with concurrent chemotherapy for patients with locally advanced carcinoma of the cervix in a single institution. METHODS: Between January 2004 and November 2008, 109 patients with stage IB2-IVA cervical carcinoma treated with IMRT and concurrent cisplatin-based chemotherapy were evaluated retrospectively. All patients received external irradiation of 45-54 Gy with an IMRT technique. High dose rate brachytherapy of 20-33.5 Gy was prescribed to point A as a local boost. Each patient received concurrent cisplatin-based chemotherapy monthly or weekly. The endpoints were overall survival (OS), local failure-free survival (LFFS) and disease-free survival (DFS). Patients were assessed for acute toxicity weekly according to the Common Toxicity Criteria for Adverse Events (CTCAE), version 3.0. Late toxicity was evaluated according to RTOG-EORTC Late Radiation Morbidity Scoring Schema. RESULTS: The median follow up time for all surviving patients was 32.5 months, with a range from 5 to 75 months. The 3-year OS, LFFS and DFS were 78.2%, 78.1% and 67.6%, respectively. Three (2.7%) patients developed grade 3 or greater acute gastrointestinal (GI) toxicity and 26 (23.9%) patients developed grade 3 or greater hematological toxicity. Five (4.6%) patients developed grade 3 or greater chronic GI toxicity and 7 (6.4%) patients developed grade 3 or greater genitourinary system toxicity. CONCLUSIONS: Good outcomes were achieved with definitive IMRT and concurrent chemotherapy for patients with locally advanced cervical cancer and the combined treatment was well tolerated with favorable acute and late toxicity.