Dataset Information

Effectiveness of High-risk Human Papillomavirus Testing for Cervical Cancer Screening in China: A Multicenter, Open-label, Randomized Clinical Trial.

ABSTRACT:

Importance

Evidence is needed regarding the introduction of high-risk human papillomavirus (hrHPV) testing into China's national cervical cancer screening program.

Objective

To evaluate hrHPV testing as a new screening modality for the national program.

Design, setting, and participants

This population-based, multicenter, open-label, randomized clinical trial took place across 20 primary health care centers in urban and rural areas across China. At least 3000 women aged 35 to 64 years per site were invited to participate, for a total of 60?732 women evaluated.

Interventions

At baseline, women were randomly assigned to cytology, hrHPV testing, or visual inspection with acetic acid and Lugol iodine (VIA/VILI) (rural only). Women who tested positive for hrHPV were randomized into cytology-triage, VIA/VILI-triage (rural only), or direct colposcopy arms. Regarding primary or triaging tests, women with cytological abnormalities or who tested positive with VIA/VILI were referred to colposcopy. After 24 months, combined screening of cytology, hrHPV testing, and VIA/VILI was performed, and all women with positive results were referred to colposcopy.

Main outcomes and measures

The primary outcomes were cervical intraepithelial neoplasia grade 2 or worse (CIN2+) and CIN3+ yields. The secondary outcome was colposcopy referral rate.

Results

A total of 60?732 women were included in this study, with median (interquartile range) age of 47 (41-52) years. Among urban women, 8955 were randomized to cytology and 18?176 to hrHPV genotyping; among rural women, 11?136 were randomized to VIA/VILI, 7080 to cytology, and 15?385 to hrHPV testing. Participants who tested positive for hrHPV with direct colposcopy had higher risk ratios for disease yields at baseline (urban hrHPV vs cytology, CIN2+ 2.2 [95% CI, 1.6-3.2] and CIN3+ 2.0 [95% CI, 1.2-3.3]; rural hrHPV vs cytology, 2.6 [95% CI, 1.9-4.0] and 2.7 [95% CI, 2.0-3.6]; rural hrHPV vs VIA/VILI, 2.0 [95% CI, 1.6-2.3] and 2.3 [95% CI, 1.8-3.1]). At 24 months, baseline-negative women in the hrHPV arm had significantly lower risk ratios than those with cytology, or VIA/VILI for CIN2+ (0.3 [95% CI, 0.2-0.5], 0.3 [95% CI, 0.2-0.6]) and CIN3+ (0.3 [95% CI, 0.1-0.6], 0.4 [95% CI, 0.2-0.8]) in rural sites. The colposcopy referral rate for hrHPV-positive rural women was reduced to 2.8% by cytology triage, with significantly higher CIN2+ yields than cytology (2.1 [95% CI, 1.3-2.6]) or VIA/VILI arm (1.6 [95% CI, 1.03-2.1]). Genotyping for hrHPV with cytology triage significantly reduced the colposcopy referral rate compared with cytology (0.8 [95% CI, 0.7-0.9]) for urban women.

Conclusions and relevance

In this randomized clinical trial, testing for hrHPV was an effective primary screening method in primary health care centers. Incorporating hrHPV testing (polymerase chain reaction-based for urban areas, hybrid capture-based for rural areas) into China's national screening program is reasonable.

Trial registration

Chinese Clinical Trial Registry Identifier: ChiCTR1900022530.

SUBMITTER: Zhang J

PROVIDER: S-EPMC7774051 | biostudies-literature | 2021 Feb

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Effectiveness of High-risk Human Papillomavirus Testing for Cervical Cancer Screening in China: A Multicenter, Open-label, Randomized Clinical Trial.

Zhang Junji J Zhao Yuqian Y Dai Yi Y Dang Le L Ma Li L Yang Chunxia C Li Yang Y Kong Linghua L Wei Lihui L Zhang Shulan S Liu Jihong J Xi Minrong M Chen Long L Duan Xianzhi X Xiao Qing Q Abulizi Guzhalinuer G Zhang Guonan G Hong Ying Y Gao Xiaohong X Zhou Qi Q Xie Xing X Li Li L Niyazi Mayinuer M Zhang Zhifen Z Tuo Jiyu J Ding Yiling Y Si Manfei M Chen Fei F Song Li L Qiao Youlin Y Lang Jinghe J

JAMA oncology 20210201 2

<h4>Importance</h4>Evidence is needed regarding the introduction of high-risk human papillomavirus (hrHPV) testing into China's national cervical cancer screening program.<h4>Objective</h4>To evaluate hrHPV testing as a new screening modality for the national program.<h4>Design, setting, and participants</h4>This population-based, multicenter, open-label, randomized clinical trial took place across 20 primary health care centers in urban and rural areas across China. At least 3000 women aged 35 ...[more]

PMID: 33377903

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Project description:The availability of human papillomavirus (HPV) DNA testing and vaccination against HPV types 16 and 18 (HPV-16,18) motivates questions about the cost-effectiveness of cervical cancer prevention in the United States for unvaccinated older women and for girls eligible for vaccination.An empirically calibrated model was used to assess the quality-adjusted life years (QALYs), lifetime costs, and incremental cost-effectiveness ratios (2004 US dollars per QALY) of screening, vaccination of preadolescent girls, and vaccination combined with screening. Screening varied by initiation age (18, 21, or 25 years), interval (every 1, 2, 3, or 5 years), and test (HPV DNA testing of cervical specimens or cytologic evaluation of cervical cells with a Pap test). Testing strategies included: 1) cytology followed by HPV DNA testing for equivocal cytologic results (cytology with HPV test triage); 2) HPV DNA testing followed by cytology for positive HPV DNA results (HPV test with cytology triage); and 3) combined HPV DNA testing and cytology. Strategies were permitted to switch once at age 25, 30, or 35 years.For unvaccinated women, triennial cytology with HPV test triage, beginning by age 21 years and switching to HPV testing with cytology triage at age 30 years, cost $78,000 per QALY compared with the next best strategy. For girls vaccinated before age 12 years, this same strategy, beginning at age 25 years and switching at age 35 years, cost $41,000 per QALY with screening every 5 years and $188,000 per QALY screening triennially, each compared with the next best strategy. These strategies were more effective and cost-effective than screening women of all ages with cytology alone or cytology with HPV triage annually or biennially.For both vaccinated and unvaccinated women, age-based screening by use of HPV DNA testing as a triage test for equivocal results in younger women and as a primary screening test in older women is expected to be more cost-effective than current screening recommendations.

Project description:BackgroundRandomized controlled trials have shown a higher sensitivity and longer negative predictive value of high-risk human papillomavirus (HPV) testing than cytology for cervical cancer screening; however, little is known about the effectiveness of HPV testing in middle-income countries. Understanding the characteristics of HPV testing may increase the priority of HPV testing in health policies. The study aims to evaluate the effectiveness of HPV testing in the national cervical cancer screening programme in China.MethodsWe performed a nationwide, population-based study using individual data from the national cervical cancer screening programme in rural China between 2015 and 2017. The analyses included 1,160,981 women aged 35-64 years who underwent cytology alone or high-risk HPV testing with cytology or genotyping triage. The main outcome was cervical intraepithelial neoplasia 2 or worse (CIN2+). We used multivariate logistic regressions and performed sensitivity analyses with propensity score matching to compare the screening positive, colposcopy referral, detection rate, and positive predictive value (PPV).ResultsThe screening positive rates for HPV testing and cytology were 10.1% and 4.0%, respectively. The per protocol colposcopy referral rate of HPV testing was significantly lower than that of cytology (3.5% vs 4.0%), and this difference was mostly due to the low referral threshold of cytology (≥ASC-US). Overall, HPV testing detected more CIN2+ (5.5 vs. 4.4 per 1000, adjusted odds ratio [aOR]=1.18, 95% confidence interval 1.11-1.25) and had a higher PPV (13.8% vs 10.9%, aOR 1.29, 95% CI 1.21-1.37) than cytology. The colposcopy referrals of HPV testing in comparison to cytology differed by income status; it significantly increased in lower-middle-income areas (3.7% vs 3.1%, aOR 1.21, 95% CI 1.17-1.25) and significantly decreased in upper-middle-income areas (3.4% vs 4.9%, aOR 0.69, 95% CI 0.67-0.71). Sensitivity analyses demonstrated the reliability and robustness of the results.ConclusionsThe introduction of HPV testing could improve both the CIN2+ detection rate and efficiency of cervical cancer screening programme, supporting the introduction of primary screening with high-risk HPV testing in China. Further study is needed to investigate the long-term effect of this change.

Project description:ObjectiveTo provide the first report on the main outcomes from the prevalence and incidence rounds of a large pilot of routine primary high risk human papillomavirus (hrHPV) testing in England, compared with contemporaneous primary liquid based cytology screening.DesignObservational study.SettingThe English Cervical Screening Programme.Participants578 547 women undergoing cervical screening in primary care between May 2013 and December 2014, with follow-up until May 2017; 183 970 (32%) were screened with hrHPV testing.InterventionsRoutine cervical screening with hrHPV testing with liquid based cytology triage and two early recalls for women who were hrHPV positive and cytology negative, following the national screening age and interval recommendations.Main outcome measuresFrequency of referral for a colposcopy; adherence to early recall; and relative detection of cervical intraepithelial neoplasia grade 2 or worse from hrHPV testing compared with liquid based cytology in two consecutive screening rounds.ResultsBaseline hrHPV testing and early recall required approximately 80% more colposcopies, (adjusted odds ratio 1.77, 95% confidence interval 1.73 to 1.82), but detected substantially more cervical intraepithelial neoplasia than liquid based cytology (1.49 for cervical intraepithelial neoplasia grade 2 or worse, 1.43 to 1.55; 1.44 for cervical intraepithelial neoplasia grade 3 or worse, 1.36 to 1.51) and for cervical cancer (1.27, 0.99 to 1.63). Attendance at early recall and colposcopy referral were 80% and 95%, respectively. At the incidence screen, the 33 506 women screened with hrHPV testing had substantially less cervical intraepithelial neoplasia grade 3 or worse than the 77 017 women screened with liquid based cytology (0.14, 0.09 to 0.23).ConclusionsIn England, routine primary hrHPV screening increased the detection of cervical intraepithelial neoplasia grade 3 or worse and cervical cancer by approximately 40% and 30%, respectively, compared with liquid based cytology. The very low incidence of cervical intraepithelial neoplasia grade 3 or worse after three years supports extending the screening interval.

Project description:ObjectivesTo provide updated evidence about the risk of cervical intraepithelial neoplasia grade 3 or higher (CIN3+) and cervical cancer after a negative human papillomavirus (HPV) test in primary cervical screening, by age group and test assay.DesignObservational study.SettingReal world data from the English HPV screening pilot's first and second rounds (2013-16, follow-up to end of 2019).Participants1 341 584 women.InterventionsCervical screening with HPV testing or liquid based cytological testing (cytology or smear tests). Women screened with cytology were referred to colposcopy after high grade cytological abnormalities or after borderline or low grade abnormalities combined with a positive HPV triage test. Women screened with HPV testing who were positive were referred at baseline if their cytology triage test showed at least borderline abnormalities or after a retest (early recall) at 12 and 24 months if they had persistent abnormalities.Main outcome measuresDetection of CIN3+ and cervical cancer after a negative HPV test.ResultsFor women younger than 50 years, second round detection of CIN3+ in this study was significantly lower after a negative HPV screen in the first round than after cytology testing (1.21/1000 v 4.52/1000 women screened, adjusted odds ratio 0.26, 95% confidence interval 0.23 to 0.30), as was the risk of interval cervical cancer (1.31/100 000 v 2.90/100 000 woman years, adjusted hazard ratio 0.44, 0.23 to 0.84). Risk of an incident CIN3+ detected at the second screening round in the pilot five years after a negative HPV test was even lower in women older than 50 years, than in three years in women younger than 50 years (0.57/1000 v 1.21/1000 women screened, adjusted odds ratio 0.46, 0.27 to 0.79). Women with negative HPV tests at early recall after a positive HPV screening test without cytological abnormalities had a higher detection rate of CIN3+ at the second routine recall than women who initially tested HPV negative (5.39/1000 v 1.21/1000 women screened, adjusted odds ratio 3.27, 95% confidence interval 2.21 to 4.84). Detection after a negative result on a clinically validated APTIMA mRNA HPV test was similar to that after clinically validated cobas and RealTime DNA tests (for CIN3+ at the second round 1.32/1000 v 1.14/1000 women screened, adjusted odds ratio 1.05, 0.73 to 1.50).ConclusionsThese data support an extension of the screening intervals, regardless of the test assay used: to five years after a negative HPV test in women aged 25-49 years, and even longer for women aged 50 years and older. The screening interval for HPV positive women who have negative HPV tests at early recall should be kept at three years.

Dataset Information

Effectiveness of High-risk Human Papillomavirus Testing for Cervical Cancer Screening in China: A Multicenter, Open-label, Randomized Clinical Trial.

Importance

Objective

Design, setting, and participants

Interventions

Main outcomes and measures

Results

Conclusions and relevance

Trial registration

Publications

Effectiveness of High-risk Human Papillomavirus Testing for Cervical Cancer Screening in China: A Multicenter, Open-label, Randomized Clinical Trial.

Similar Datasets

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