Clinical Researches
Performance of vaginal self-sampling high-risk HPV genotyping as primary and combining cytology or viral load as secondary in cervical cancer screening
Guo Chunlei, Luo Hongxue, Wang Chun, Qu Xinfeng, Yang Bin, Belinson JL, Du Hui, Wu Ruifang
Published 2021-04-25
Cite as Chin J Obstet Gynecol, 2021, 56(4): 271-279. DOI: 10.3760/cma.j.cn112141-20200824-00357
Abstract
ObjectiveTo evaluate the efficacy of high-risk HPV (HR-HPV) genotyping with vaginal self-sampling in primary screening and combining cytology or viral load for HR-HPV positive as secondary screening strategies.
MethodsThe data referring to HR-HPV genotyping of self-collected sample with mass array matrix-assisted laser desorption-ionization time-of-flight mass spectrometry (MALDI-TOF-MS), HR-HPV viral load of physician-collected sample with hybrid capture Ⅱ (HC-Ⅱ), liquid-based cytology and histology of 8 556 women were from Shenzhen cervical cancer screening trial Ⅱ (SHENCCAST-Ⅱ) conducted between April 2009 and April 2010. The data were reanalyzed to determine the sensitivity and specificity to cervical intraepithelial neoplasia (CIN) of grade 2 or worse (CIN Ⅱ+), CIN of grade 3 or worse (CIN Ⅲ+) when HR-HPV genotyping combining with colposcopy as primary screening strategy based on varied HR-HPV subtype (strategy 1, including 5 sub-strategies: 1a: HPV 16/18 positive; 1b: HPV 16/18/58 positive; 1c: HPV 16/18/58/31/33 positive; 1d: HPV 16/18/58/31/33/52 positive; 1e: any HR-HPV positive). The data were also compared to determine the efficacy of cytology (strategy 2, including 5 sub-strategies: 2a, 2b, 2c, 2d, 2e) or HR-HPV viral load (strategy 3, including 4 sub-strategies: 3a, 3b, 3c, 3d) of physician-collected sample as a triage with HR-HPV genotyping for self-sampling HR-HPV positives.
Results(1) The HR-HPV positive rate was 13.77% (1 178/8 556) in the self-collected samples of 8 556 pregnant women. Of them,the prevalences of HPV 16/18, HPV 16/18/58, HPV 16/18/58/31/33 and HPV 16/18/58/31/33/52 were 3.16% (270/8 556), 5.14% (440/8 556), 6.66% (570/8 556) and 9.81% (839/8 556), respectively. The HR-HPV viral load ≥10 relative light units/control (RLU/CO) was 8.87%(759/ 8 556), while cytological results ≥atypical squamous cell of undetermined signification (ASCUS) were 12.05% (1 031/8 556). (2) The strategy 1e had the highest sensitivities for CIN Ⅱ+, CIN Ⅲ+ which were 92.70% and 94.33%,respectively,among 14 sub-strategies,while the lowest specificity and positive predictive value (PPV). Meanwhile,the required colposcopy referral rates were much higher than other 13 sub-strategies (13.77%). The other 4 sub-strategies of strategy 1 (1a, 1b, 1c, 1d), strategy 1a had the highest specificities for CIN Ⅱ+ and CIN Ⅲ+ (97.92%, 97.69%, respectively), while 1d had the highest sensitivities for CIN Ⅱ+ and CIN Ⅲ+ (88.41%, 92.20%, respectively). (3) Both strategies of referring self-sampling HPV 16/18 positives for immediate colposcopy followed by triage physician-collected sample cytology (≥ASCUS) or viral load (≥10 RLU/CO) for non-HPV 16/18 positives had significantly higher sensitivity and specificity for CIN Ⅱ, CIN Ⅲ+, as well as lower referral rates (strategy 2a and 3a). Additionally, based on these two secondary screening strategies, cumulatively using the other four HR-HPV (HPV 58, 31, 33 and 52) positives as triage for immediate colposcopy showed an enhanced sensitivity.
ConclusionsPrimary HR-HPV cervical cancer screening strategy based on self-sampling with triage of cytology (≥ASCUS) or viral load (≥10 RUL/CO) provides a good balance among sensitivity, specificity for CIN Ⅱ+ and CIN Ⅲ+ and the number of tests required, referral rates. The efficacy of HR-HPV genotyping combining cytology or viral load secondary screening strategies will have a spiral escalation when HPV 58, 31, 33, 52 are included.
Key words:
Uterine cervical neoplasms; Vaginal smears; Biopsy; Papillomaviridae; Viral load
Contributor Information
Guo Chunlei
Department of Obstetrics and Gynecology, Peking University Shenzhen Hospital, Institute of Obstetrics and Gynecology, Shenzhen Peking University-Hong Kong University of Science and Technology Medical Center, Shenzhen Key Laboratory on Technology for Early Diagnosis of Major Gynecological Diseases, Shenzhen 518000, China
Luo Hongxue
Department of Obstetrics and Gynecology, Peking University People′s Hospital, Beijing 100044, China
Wang Chun
Department of Obstetrics and Gynecology, Peking University Shenzhen Hospital, Institute of Obstetrics and Gynecology, Shenzhen Peking University-Hong Kong University of Science and Technology Medical Center, Shenzhen Key Laboratory on Technology for Early Diagnosis of Major Gynecological Diseases, Shenzhen 518000, China
Qu Xinfeng
Department of Obstetrics and Gynecology, Peking University Shenzhen Hospital, Institute of Obstetrics and Gynecology, Shenzhen Peking University-Hong Kong University of Science and Technology Medical Center, Shenzhen Key Laboratory on Technology for Early Diagnosis of Major Gynecological Diseases, Shenzhen 518000, China
Yang Bin
Preventive Oncology International, Inc, Shaker Heights, USA and Cleveland Clinic, Women's Health Institute, Cleveland, OH, USA, 44109
Belinson JL
Preventive Oncology International, Inc, Shaker Heights, USA and Cleveland Clinic, Women's Health Institute, Cleveland, OH, USA, 44109
Du Hui
Department of Obstetrics and Gynecology, Peking University Shenzhen Hospital, Institute of Obstetrics and Gynecology, Shenzhen Peking University-Hong Kong University of Science and Technology Medical Center, Shenzhen Key Laboratory on Technology for Early Diagnosis of Major Gynecological Diseases, Shenzhen 518000, China
Wu Ruifang
Department of Obstetrics and Gynecology, Peking University Shenzhen Hospital, Institute of Obstetrics and Gynecology, Shenzhen Peking University-Hong Kong University of Science and Technology Medical Center, Shenzhen Key Laboratory on Technology for Early Diagnosis of Major Gynecological Diseases, Shenzhen 518000, China