Cervical Cancer Screening In China Research Articles

Validation of the 2019 American Society of Colposcopy and Cervical Pathology Online Cervical Cancer Screening Program via 9 Large-Cohort Data of Chinese Women.

The aim of the study is to validate the applicability and performance of the 2019 US risk-based guideline for Chinese women. We analyzed 10,055 cases with data on human papillomavirus testing, cytology, and pathologically confirmed diagnosis (analysis-set). According to the 2019 US risk-based guideline, we recorded the risk value and triage recommendations for each case. Then, we assessed the concordance of the guideline triage recommendations with pathology diagnosis for the relevant case from the real-world projects. Among the analysis-set, 9,495 cases with an estimated risk value were identified as analysis cohort while the remaining 560 cases were cataloged as "special cases." Among the analysis cohort, 960 and 526 cases were pathologically confirmed as cervical intraepithelial neoplasia (CIN) 2+ and CIN3+, respectively. The US risk-based guideline recommended colposcopy or more aggressive interventions (Colp+) for 86.8% (833/960) of the CIN2+ and 95.8% (504/526) of the CIN3+ cases, with 87.1% sensitivity and 82.5% specificity for CIN3+ cases (AUC = 0.926, p < .0001). The US risk-based recommended no-Colp for 98.0% (6,142/6,269) of the pathologically confirmed CIN1 or benign cases. In addition, 97.3% (545/560) of the "special cases" cases were recommended as Colp+. The 2019 US risk-based guideline works well with satisfied clinical sensitivity for CIN2+ and CIN3+ and seems applicable for cervical cancer screening in China.

HPV self-sampling for cervical cancer screening in China: A multi-center study

BackgroundHuman papillomavirus (HPV) self-sampling is a new method for collecting cervical isolated cells, but research been carried out in multi-ethnic and multi-regional areas of China is scarce. ObjectivesWe aimed to evaluate the accuracy and acceptability of HPV self-sampling and analyze the characteristics of HPV infection. Study designWomen aged 25–65 years were recruited from 8 provinces in China. Women underwent clinician-sampling and self-sampling and were asked to complete a 65-question questionnaire on their acceptance of HPV self-sampling. The paired samples were analyzed for 23 genotypes of HPV by polymerase chain reaction. Results5551 women were recruited, of which 5417 were eligible for analysis. 3163 women have completed and submitted the questionnaire. The top five infection genotypes were HPV 52, 58, 16, 39, and 68. The highest infection rate was in the 25–30 years group. The crude agreement between self-sampling and clinician-sampling was 93.06 %. 43.79 % of women preferred self-sampling over clinician-sampling, and 67.59 % preferred doing self-sampling at the hospital. ConclusionHPV self-sampling could be an effective supplement to traditional cervical screening in China. Clinicians’ advocacy, timely reminders and guidance for women with abnormal self-sampling results are needed. In addition, new vaccination and cervical screening recommendations might be adjusted to fit populations with different characteristics.

Effectiveness of high-risk human papillomavirus genotyping for cervical cancer screening. A multicentre screening cohort study in rural China.

This study aimed to assess the effectiveness of high-risk human papillomavirus (HR-HPV) primary testing for cervical cancer screening in China's rural areas. Women aged 21-64 years were recruited. Cervical cytology was diagnosed following the Bethesda 2001 classification system, HPV infection (HR-HPV, HPV-16, HPV-18, and other 12 genotypes) identified by Cobas-4800, and colposcopy and biopsy performed when required. Primary outcomes were defined as the cumulative incidence of cervical intraepithelial neoplasia grade 2/3/higher (CIN2/3+) and its relative risk at baseline and at the 36-month follow-up. The study included 9,218 women; mean age was 45.15 years (SD: 8.74); 81% completed the follow-up. The most frequent type of cytological lesions (12.4% ) were ASCUS (8.4%) and LSIL (2.2%). HR-HPV infection (16.3%) was more prevalent in HPV-16 than in HPV-18 (3 vs 1.5%); a positive relationship with the severity of the lesions, from 29.8% in ASCUS to 89.6% in HSIL was found. At baseline, 3.5% of the patients underwent colposcopy; 20% had a positive diagnosis. At the 36-month follow-up, the cumulative incidences of CIN2+ and CIN3+ were higher in women with HR-HPV infection (16.9 vs 0.5% and 8.2 vs 0.2%). The relative risk of CIN2/3+ was lower in HR-HPV-negative women compared to those with a negative cytology at baseline (0.4; 95%CI: 0.3-0.4). High-risk HPV-based screening may significantly reduce the risk of CIN2/3+ compared with cytology testing. This may be a new resource for public health demands in China's rural areas.

Impact of high-performance human papillomavirus testing to improve cervical cancer screening in China: a prospective population-based multicentre cohort study

ObjectivesThe aim of the study was to evaluate the clinical performance of HBRT-H14, a real-time PCR-based assay that separates human papillomavirus (HPV) 16 and HPV18 from 12 other high-risk (HR) HPV types, in population according to Chinese guideline. MethodsA total of 9829 eligible women aged 21–64 years from Henan, Shanxi, and Guangdong provinces were performed by HBRT-H14 testing and liquid-based cytology (LBC) screening at baseline and followed up for 3-year. The sensitivity, specificity, positive predictive value (absolute risk), and negative predictive value of LBC diagnosis and HPV testing were calculated for cervical intraepithelial neoplasia grade 2 or worse (CIN2+) Lesions. ResultsAt baseline, 80 (0.81%) participants were diagnosed with CIN2+. HR-HPV with reflex LBC had a significantly higher sensitivity (78/80, 97.50% [95% CI, 91.34–99.31%] vs. 62/80, 77.50% [67.21–85.27%], McNemar's test p < 0.001), and a slightly lower specificity (8528/9749, 87.48% [86.80–88.12%] vs. 8900/9749, 91.29% [90.72–91.83%], McNemar's test p < 0.001) than LBC with reflex HR-HPV for CIN2+. 7832 (79.6%) participants completed 3-year follow-up and 172 (2.20%) participants were cumulatively diagnosed with CIN2+. Compared with LBC with reflex HR-HPV, HR-HPV with reflex LBC significantly increased the sensitivity (161/172, 93.60% [88.91–96.39%] vs. 87/172, 50.58% [43.18–57.96%], McNemar's test p < 0.001), but marginally decreased the specificity (6776/7660, 88.46% [87.72–89.16%] vs. 6933/7660, 90.51% [89.83–91.15], McNemar's test p < 0.001). In addition, the absolute 3-year risk of CIN2+ in HPV16/18-positive individuals was as high as 33% (80/238), whereas the risk in the HPV-negative population was only 0.16% (11/6787), much lower than those in the negative for intraepithelial lesion or malignancy population (1.21%, 85/7018). Moreover, similar results were found in women ≥30 years old. DiscussionThe study has indicated that HBRT-14 has a reliable clinical performance for use in cervical screening. The validated HPV test would improve the quality of population screening.

Chinese expert consensus on the use of human papillomavirus nucleic acid testing for cervical cancer screening (2022)

China is currently in a critical period of accelerating the elimination of cervical cancer, and scaling up screening coverage with high-quality methods is one of the main approaches to achieve this goal. World Health Organization (WHO) recommended human papillomavirus (HPV) nucleic acid testing as the preferred primary screening method of cervical cancer. However, no guidelines exist for its use in cervical cancer screening in China. Therefore, Branch of Cancer Prevention and Control, Chinese Preventive Medicine Association, Chinese Obstetrics and Gynecology Association Colposcopy and Cervical Neoplasia Committee, Chinese Society of Colposcopy and Cervical Pathology of China Health Birth Science Association, Beijing Medical Doctor (Technician) Society of Laboratory Medicine, and the editorial board of the National Medical Journal of China convened more than 50 domestic experts from multiple disciplines, including public health, obstetrics and gynecology, laboratory medicine, and pathology, to form a consensus based on domestic and international guidelines, medical evidence, and China's actual situation. These experts recommend HPV nucleic acid testing as the primary method for cervical cancer screening in China, and provide scientific suggestions on the pre-implementation assessment and preparation, specific applications and target populations, laboratory operating procedures, and post-implementation monitoring and assessment for the cervical cancer screening. These recommendations aim to promote a comprehensive, in-depth, standardized, orderly and high-quality development of HPV nucleic acid testing in China, for providing strong support for accelerating cervical cancer elimination in China.

Clinical performance of a newly developed domestic urine-based HPV test for cervical cancer screening in China.

Although urine-based human papillomavirus(HPV) detection is promising in cervical cancer screening, it has not yet been well-developed. Women aged 30-65 were invited to participate in the current study to provide one urine and two paired vaginal samples. Urine was detected by polymerase chain reaction(PCR)-based HPV test (urine-based HPV test). Two vaginal samples were tested by careHPV and GenPlex® HPV genotyping assay, respectively. Women with vaginal HPV positive were called back for colposcopy and biopsied if clinically indicated. The consistency was 79.0% (κ = 0.563) and 80.5% (κ = 0.605) between the urine-based HPV test, careHPV test, and GenPlex® HPV genotyping assay. Against CIN2detection, the careHPV test showed 77.4% sensitivity, and 71.0% specificity, while the GenPlex® HPV genotyping assay had a sensitivity of 100% and a specificity of 58.7%. For urine-based HPV test, the corresponding rates were 96.8% and 58.7%. Moreover, no significant differences were observed between the urine-based HPV test and careHPV test (p = 0.3395) and GenPlex® HPV genotyping assay (p = 0.338). The newly developed urine-based HPV test demonstrated acceptable consistency and comparable clinical performance with referenced HPV tests for vaginal samples. Therefore, urine-based HPV detection could be a useful alternative for women with difficulties to access cervical cancer screening.

Cost-effectiveness of artificial intelligence-assisted liquid-based cytology testing for cervical cancer screening in China

The 2021 World Health Organization (WHO) guidelines for cervical cancer screening recommend human papillomavirus (HPV) DNA or mRNA testing. Artificial intelligence (AI)-assisted liquid-based cytology (LBC) systems also have the potential to facilitate rapid scale-up of cervical cancer screening. We aimed to evaluate the cost-effectiveness of AI-assisted LBC testing, compared with the manual LBC and HPV-DNA testing, for primary cervical cancer screening in China. We developed a Markov model for a cohort of 100,000 women aged 30 years over a lifetime to simulate the natural history of cervical cancer progression. We evaluated the incremental cost-effectiveness ratios (ICER) of 18 screening strategies (a combination of the three screening methods with six screening frequencies) from a healthcare provider's perspective. The willingness-to-pay threshold (US$30,828) was chosen as three times the Chinese per-capita gross domestic product in 2019. Univariate and probabilistic sensitivity analyses were performed to examine the robustness of the results. Compared with no screening, all 18 screening strategies were cost-effective, with an ICER of $622-24,482 per quality-adjusted life-year (QALY) gained. If HPV testing after scaling up to population level screening costs $10.80 or more, screening once every 5 years using AI-assisted LBC would be the most cost-effective strategy with an ICER of $8790/QALY gained compared with the lower-cost non-dominated strategy on the cost-effectiveness frontier. Its probability of being cost-effective was higher (55.4%) than other strategies. Sensitivity analyses showed that the most cost-effective strategy would become AI-assisted LBC testing once every 3 years if the sensitivity (74.1%) and specificity (95.6%) of this method were both reduced by ≥10%. The most cost-effective strategy would become HPV-DNA testing once every 5 years if the cost of AI-assisted LBC was more expensive than manual LBC or if the HPV-DNA test cost is slightly reduced (from $10.8 to <$9.4). AI-assisted LBC screening once every 5 years could be more cost-effective than manually-read LBC. Using AI-assisted LBC could have comparable cost-effectiveness to HPV DNA screening, but the relative pricing of HPV DNA testing is critical in this result. National Natural Science Foundation of China, National Key R&D Program of China.

Using Delphi method to develop Chinese women's cervical cancer screening intention scale based on planned behavior theory.

Cervical cancer is the most common malignant tumor in women with a high mortality rate. However, the awareness and participation of women in cervical cancer screening were not high, and rare attention was paid to cervical cancer screening. The extensive promotion and execution of cervical cancer screening in China are still facing difficulties. In order to fully comprehend and evaluate the barriers and promote factors of cervical cancer screening in women, the objective of this study was to develop a scientifically sound and clinically useful Chinese cervical cancer screening intention scale. This study would allow for the development of targeted interventions which may contribute to the increase of individual participation in cervical cancer screening going forward. This study used the Delphi method to construct a Chinese cervical cancer screening intention scale based on the theory of planned behavior (TPB) and evaluate its validity. The study was based on the overview of the TPB questionnaire proposed by Ajzen, and was conducted through the literature search and two rounds of the Delphi expert consultation. According to the literature search published from 2012 to 2022, the scale item pool was established and a questionnaire was designed. A survey of 16 experts from 6 different provinces, cities and regions in China was conducted, and the Delphi technique was used to collect and analyze expert opinions data. The final scale consisted of 4 dimensions and 23 items. The response rates in two rounds of expert consultation were 80% and 93.75%, respectively, with authority coefficients of 0.928 and 0.930. Variation coefficients varied from 0.07 to 0.21. Dimensions included "attitude towards behavior", "subjective norm", "perceived behavioral control" and "behavioral intention". Women's cervical cancer screening intentions could be assessed with the scale, since it had high validity and reliability, as well as high authority and coordination, meanwhile affording explanations and improving the efficiency of interventions.

Performance of the Human Papillomavirus E6/E7 mRNA Assay in the Primary Screening of Cervical Cancer: Opportunistic Screening in Fujian, China.

PurposeA high-risk human papillomavirus E6/E7 mRNA (HR-HPV mRNA) assay is widely used in cervical cancer screening in China. However, it is still unclear whether stand-alone HR-HPV mRNA testing is sufficient for primary screening. The purpose of this study was to investigate the feasibility of a stand-alone HR-HPV mRNA assay for primary screening of cervical cancer.MethodsWomen aged 21 and older were recruited in Fujian Province, China, from January 2020 to January 2022. Cervical exfoliated cells were collected for cervical cytology and HR-HPV mRNA assays, and women with positive results on either assay were referred for colposcopy. The screening effectiveness of the assay was calculated based on the cervical histology. When comparing the efficacy of the different screening strategies, only women aged 25 and older were included.ResultsA total of 9927 women were recruited. This study identified 217 cases of high-grade squamous intraepithelial disease or worse (HSIL+). The overall age-specific HR-HPV infection rate showed a U-shaped distribution. The sensitivity of the HR-HPV mRNA assay to identify CIN2+ and CIN3+ was 97.2% and 97.9%, respectively, which was significantly higher than that of cytology (82.9% and 88.6%, P<0.001 and 0.002). The sensitivity of the HR-HPV mRNA primary screening strategy to identify CIN2+ and CIN3+ was 92.2% and 94.3%, respectively, which was similar to the co-testing strategy (P=0.336 and 0.394) and higher than the cytology primary screening (P=0.002 and 0.048). In addition, the HR-HPV primary screening strategy had a lower referral rate for colposcopy than cytology primary screening (5.4% vs 6.6%, P<0.001), and the screening cost was lower than co-testing ($29,594.3 per 1000 screened women vs $55,140 per 1000 screened women, P<0.001).ConclusionIn conclusion, the detection of CIN2+/CIN3+ by HR-HPV mRNA is both specific and sensitive. It may be suitable for primary screening of cervical cancer in China.

Performance of human papillomavirus E6/E7 mRNA assay for primary cervical cancer screening and triage: Population-based screening in China.

ObjectiveCervical cancer screening is very important in the prevention and treatment of cervical cancer. In China, the cervical screening strategy needs to be improved. To explore a suitable cervical screening strategy in China, we evaluated the performance of the human papillomavirus (HPV) E6/E7 mRNA (Aptima HPV (AHPV)) assay in primary screening and different triage strategies for women undergoing routine cervical screening.MethodsA total of 10,002 women aged 35 to 65 years of age were recruited in Liaoning Province and Qingdao City, China. Specimens were tested by liquid-based cytology (LBC) and the AHPV assay, and women who tested positive on any test were referred for colposcopy. Genotyping was performed on all high-risk HPV (HR-HPV)-positive samples. Test characteristics were calculated based on histological review.ResultsWe identified 109 women with high-grade squamous intraepithelial lesion or worse (HSIL+), including six with cervical cancer. The sensitivity of AHPV was clearly higher than that of LBC (92.7 [95% CI: 87.2, 97.2] vs. 67.9 [95% CI: 59.6, 76.1], p < 0.001). The specificity of AHPV was 93.0 (95% CI: 92.5, 93.5), which was lower than that of LBC (95.2 [95% CI: 94.8, 95.6], p < 0.001). There was no statistical difference between the positive predictive value of AHPV and LBC (13.5 [95% CI: 11.2, 16.2] vs. 14.3 [95% CI: 11.4, 17.6], p = 0.695). The difference of area under the curve (AUC) values between the AHPV test (0.928 [95% CI: 0.904, 0.953]) and LBC test (0.815 [95% CI: 0.771, 0.860]) in detecting HSIL+ was statistically significant (p < 0.001). Finally, among the three triage strategies, both the sensitivity (73.4 [95% CI: 65.1, 81.7]) and AUC (0.851 [95% CI: 0.809, 0.892]) of AHPV genotyping with reflex LBC triage were the greatest.ConclusionIn summary, the AHPV assay is both specific and sensitive for detecting HSIL+ and may be suitable for use in primary cervical cancer screening in China. AHPV genotyping with reflex LBC triage may be a feasible triage strategy.

Breast and cervical cancer screening adherence in Jiangsu, China: An ecological perspective.

BackgroundHigh screening coverage can effectively reduce the mortality in breast and cervical cancer. Further research on extending the coverage of breast and cervical cancer screening in China is required. This study explored factors influencing women's “two-cancer” screening service utilization using an ecological approach.MethodsData were obtained from the National Health Services Survey (NHSS) conducted in 2018 in Jiangsu, China. A total of 3,500 women aged 18–64 years were included in the analysis. Chi-squared test, hierarchical multiple logistic regression analysis, and binary logistic regression analysis were performed.ResultsIn total, 44.1% of the women had been screened for breast cancer (BC) and 40.9% for cervical cancer (CC). Breast cancer screening (BCS) and cervical cancer screening (CCS) differed significantly in the following common categories: age, gestational experiences, chronic disease status, body mass index (BMI), exercise, health checkup, marital status, number of children, employment, education, family doctors, and health records. In the results of hierarchical multiple logistic regression analysis, the explanatory power of the final model was 37.5% and the area under the receiver operating characteristic curve was 0.812. The results showed that being in the age group of 35–64 years, having gestational experiences, having chronic diseases, exercising, having a health checkup, being married, having children, and being employed were statistically significant positive predictors of “two-cancer” screening adherence. The household size was a barrier. For BCS, obesity was also a negative factor, and a higher overall self-related health status was a positive factor. Being married and living in households of three or more families were not predictors. For CCS, having health records was also positively significant, while having chronic disease did not influence adherence.ConclusionThe findings provide an ecological explanation for women's BCS and CCS service utilization. Both proximal and distal factors should be considered to achieve a high coverage rate.

Joint effects of HPV-related knowledge and socio-demographic factors on HPV testing behaviour among females in Shenzhen.

Limited population-based studies explore the utilization and associated barriers or facilitators to cervical cancer screening in China. We attempted to investigate the associations of socio-demographic factors, HPV specific knowledge with HPV testing behaviour in Shenzhen, China. A citywide cross-sectional survey was conducted from January to June 2015 in Shenzhen city by using a multistage stratified cluster sampling method. Socio-demographic information, awareness and specific knowledge of HPV, practice of HPV testing, and HPV vaccination-related attitude were collected. Multivariate logistic regression model was used to analyse possible associations. Approximately one third of total 8639 women aged from 30 to 60 years old had ever received HPV testing. Overall, 67.6% of all participants demonstrated low knowledge level of HPV. High HPV knowledge level was significantly associated with HPV testing behaviour (odds ratio: 3.792, 95% confidence interval: 3.400-4.230). The impact of residence and education on testing behaviour only turned to be significant if women had low level of HPV knowledge (P for multiplicative interactions: 0.001 and <0.001, respectively), whereas monthly income exerted promotion effects apparently among those with high knowledge level (P for multiplicative interaction: 0.037). Our study revealed gaps in HPV knowledge and screening participation among Chinese women, and provided novel clues that women with high HPV knowledge level would be more appeal to involve in HPV testing behaviour. The influence of HPV-related knowledge on HPV testing also lies in the joint effects with socio-demographic factors, including residence, education and monthly income.

Effect of introducing human papillomavirus genotyping into real-world screening on cervical cancer screening in China: a retrospective population-based cohort study.

Background:China’s Fujian Cervical Pilot Project (FCPP) transitioned cervical cancer screening from high-risk human papillomavirus (HR-HPV) nongenotyping to genotyping. We investigated the clinical impact of this introduction, comparing performance indicators between HR-HPV genotyping combined with cytology screening (HR-HPV genotyping period) and the previous HR-HPV nongenotyping combined with cytology screening (HR-HPV nongenotyping period).Methods:A retrospective population-based cohort study was performed using data from the FCPP for China. We obtained data for the HR-HPV nongenotyping period from 1 January 2012 to 31 December 2013, and for the HR-HPV genotyping period from 1 January 2014 to 31 December 2016. Propensity score matching was used to match women from the two periods. Multivariable Cox regression was used to assess factors associated with cervical intraepithelial neoplasia of grade 2 or worse (CIN2+). The primary outcome was the incidence of CIN2+ in women aged ⩾25 years. Performance was assessed and included consistency, reach, effectiveness, adoption, implementation and cost.Results:Compared with HR-HPV nongenotyping period, in the HR-HPV genotyping period, more CIN2+ cases were identified at the initial screening (3.06% versus 2.32%; p < 0.001); the rate of colposcopy referral was higher (10.87% versus 6.64%; p < 0.001); and the hazard ratio of CIN2+ diagnosis was 1.64 (95% confidence interval, 1.43–1.88; p < 0.001) after controlling for health insurance status and age. The total costs of the first round of screening (US$66,609 versus US$65,226; p = 0.293) were similar during the two periods. Higher screening coverage (25.95% versus 25.19%; p = 0.007), higher compliance with age recommendations (92.70% versus 91.69%; p = 0.001), lower over-screening (4.92% versus 10.15%; p < 0.001), and reduced unqualified samples (cytology: 1.48% versus 1.73%, p = 0.099; HR-HPV: 0.57% versus 1.34%, p < 0.001) were observed in the HR-HPV genotyping period.Conclusions:Introduction of an HR-HPV genotyping assay in China could detect more CIN2+ lesions at earlier stages and improve programmatic indicators. Evidence suggests that the introduction of HR-HPV genotyping is likely to accelerate the elimination of cervical cancer in China.

Effectiveness of High-risk Human Papillomavirus Testing for Cervical Cancer Screening in China

Evidence is needed regarding the introduction of high-risk human papillomavirus (hrHPV) testing into China's national cervical cancer screening program. To evaluate hrHPV testing as a new screening modality for the national program. 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. 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. The primary outcomes were cervical intraepithelial neoplasia grade 2 or worse (CIN2+) and CIN3+ yields. The secondary outcome was colposcopy referral rate. 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. 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. Chinese Clinical Trial Registry Identifier: ChiCTR1900022530.

DNA methylation markers as triage test for the early identification of cervical lesions in a Chinese population.

Objective strategies are required in cervical cancer screening. We have identified several DNA methylation markers with high sensitivity and specificity to detect cervical intraepithelial neoplasia 2 or worse (CIN2+) in Dutch women. Our study aims to analyze the diagnostic characteristics of these markers in a Chinese cohort. A total of 246 liquid‐based cytology samples were included, of which 205 women underwent colposcopy due to an abnormal cytology result (atypical squamous cells of undetermined significance [ASCUS] or worse), while 227 were tested high‐risk human papillomavirus (hrHPV) positive. All six individual markers (ANKRD18CP, C13ORF18, EPB41L3, JAM3, SOX1 and ZSCAN1) showed enhanced methylation levels and frequency with increasing severity of the underlying lesion (P ≤ .001). In cytological abnormal women, sensitivity to detect CIN2+ was 79%, 76% and 72% for the three panels (C13ORF18/EBP41L3/JAM3, C13ORF18/ANKRD18CP/JAM3 and ZSCAN1/SOX1, respectively), with a specificity of 57%, 65% and 68%. For the first two panels, these diagnostic characteristics were similar to the Dutch cohort, while for ZSCAN1/SOX1 the sensitivity was higher in the Chinese cohort, but with a lower specificity (both P < .05). In hrHPV‐positive samples, similar sensitivity and specificity for the detection of CIN2+ were found as for the abnormal cytology cohort, which were now all similar between both cohorts and non‐inferior to HPV16/18 genotyping. Our analysis reveals that the diagnostic performances are highly comparable for C13ORF18/EBP41L3/JAM3 and C13ORF18/ANKRD18CP/JAM3 methylation marker panels in both Chinese and Dutch cohorts. In conclusion, methylation panels identified in a Dutch population are also applicable for triage testing in cervical cancer screening in China.

The Potential Benefits of HPV E6/E7 mRNA Test in Cervical Cancer Screening in China.

This study aims to evaluate the clinical performance of the HPV E6/E7 mRNA test in cervical cancer screening in China. A hospital-based study was conducted with mRNA, DNA, and liquid-based cytology (LBC) as primary screening tests. Each woman with a positive result received colposcopy with lesion-targeted-biopsy. Histopathological diagnosis was used as the gold standard. The total agreement of HPV DNA and mRNA was 90.7% (95%CI: 87.9, 92.9) with a kappa value of 0.81. The positive rates of HPV DNA, mRNA, and LBC increased with the severity of histopathology diagnosis, from 25.5, 19.1, and 11.4% in normal to 100.0% in SCC, respectively. The sensitivities for mRNA to detect CIN2+ and CIN3+ were 93.8% (95%CI: 89.7–96.4) and 95.7% (95%CI: 91.3–97.9), respectively, which were not different from HPV DNA testing (95.7% [95%CI: 92.0–97.7], 96.3% [95%CI: 92.1–98.3]), but higher than LBC (80.4% [95%CI: 74.5–85.2] and 88.8% [95%CI: 83.0–92.8]). The specificities for mRNA to detect CIN2+ (79.0% [95%CI: 74.2–83.0]) and CIN3+ (70.5% [95%CI: 65.7–74.9]) were higher than HPV DNA testing (71.0% [95%CI: 65.9–75.7], 62.8% [95%CI: 57.8–67.5]), but lower than LBC (84.5% [95%CI: 80.1–88.0] 79.8% [95%CI: 75.4–83.6]). All tests were more effective in women older than 30 years. HPV mRNA test showed excellent agreement with the DNA test, with similar sensitivity and a higher specificity in detecting high-grade cervical lesions. It is promising that mRNA test could be used for the national cervical cancer screening to reduce false positive without losing sensitivity.

Cost-effectiveness and accuracy of cervical cancer screening with a high-risk HPV genotyping assay vs a nongenotyping assay in China: an observational cohort study

BackgroundNew screening techniques may affect the optimal approachesfor the prevention of cervical cancer. We evaluated the cost-effectiveness and accuracy of alternative screening strategies to provide evidence for cervical cancer screening guidelines in China.MethodsIn total, 32,306 women were enrolled. The current screening with Cervista® high-risk human papillomavirus (HR-HPV) nongenotyping and cytology cotesting (Cervista® cotesting) was compared with PCR-reverse dot blot HR-HPV genotyping and cytology cotesting (PCR-RDB cotesting). All eligible participants were divided into Arm 1, in which both HR-HPV assays were performed, and Arms 2 and 3, in which the PCR-RDB HPV or Cervista® HR-HPV assay, respectively, was performed. Outcome indicators included the cases, sensitivity, negative predictive value (NPV), colposcopy referral rate and cost of identifying cervical intraepithelial neoplasia of grade 2/3 or worse (CIN2+/CIN3+).ResultsAmong the eligible participants, 18.4% were PCR-RDB HR-HPV-positive, while 16.9% were Cervista® HR-HPV-positive, which reflects good agreement (k = 0.73). PCR-RDB cotesting identified more CIN3+ cases than Cervista® cotesting in the first round of screening in Arm 1 (37 vs 32) and Arms 2/3 (252 vs 165). The sensitivity and NPV of PCR-RDB cotesting for identifying CIN3+ in Arm 1 (sensitivity: 94.9% vs 86.5%; NPV: 99.9% vs 99.7%) and Arms 2/3 (sensitivity: 95.1% vs 80.9%; NPV: 99.9% vs 99.6%) were higher than those of Cervista® cotesting, but the cost was similar.ConclusionsThe PCR-RDB HR-HPV genotyping and Cervista® HR-HPV assay results were consistent. PCR-RDB cotesting possesses optimal cost-effectiveness for cervical cancer screening in China, which has the highest number of cases globally but low screening coverage.

Diagnostic Yield and Performance of a Large Population-Based Cervical Cancer Screening Program in High-Risk Rural China.

Primary cervical cancer screening by liquid-based cytology alone or with adjunctive HPV testing are available worldwide. However, little if any information is available about cervical cancer diagnostic yield of population-based cervical cancer screening in China. In response to it, we conducted a large prospective study on 40,000 women cervical cancer screening within six-month period in rural Shanxi Province, where has been reported as the highest cervical cancer rates in China. A standard cross-sectional survey by self-completed questionnaire was collected and followed by the liquid-based cytology screening. Follow-up biopsy with the diagnosis of cervical intraepithelial neoplasia 2 or higher lesion (CIN2+) were analyzed. Of initial 40,000 women participating in this study, 6.76% (2702/40,000) women had ASC-US or higher cytology screening results with ASC/SIL ratio at 6.14 (2381:388). Among them, 1.96% (782/40,000) women were found CIN lesions (95% CI, 1.68-2.23%) on confirmatory biopsies, including 0.55% (218/40,000) CIN2+ and 19 SCCa (47.5/100,000, 95% CI, 29-74/100,000). Women in Yangqu County had lower ASC/SIL ratio, but higher CIN2+ detection rate in comparison with that of Jiexiu County (6.69 vs. 8.84 and 56.7% vs. 43.9%), which reflects the cervical cancer distribution in different populations and regions. Analysis in age-stratified cytology results indicated women aged 60-65 years had the highest incidence of cytologic abnormality among all the age group; likewise, women aged >50 years were at higher risk in developing cervical high grade dysplasia or cancer than women aged <50 years (0.82% vs. 0.49%). This large-scale cervical cancer screening study provided important references as the instructive for establishing the nation-wide cervical cancer screening strategy.

Clinical Performance of Human Papillomavirus Testing and Visual Inspection With Acetic Acid in Primary, Combination, and Sequential Cervical Cancer Screening in China.

World Health Organization guidelines recommend screening with human papillomavirus (HPV) testing followed by either treatment of all HPV-positives, or by visual inspection (VIA) for triage to treatment, citing insufficient evidence to recommend either strategy over the other. We assessed VIA and HPV testing individually, in combination (HPV-VIA cotesting), and as triage models. Three thousand women were screened in Inner Mongolia, China, concurrently with HPV testing and VIA in a real population setting. Screen-positive women underwent colposcopy, and biopsy, if indicated. Accuracy of screening algorithms for cervical intraepithelial neoplasia grade 2 or higher (CIN-2+) was calculated after controlling for verification bias. HPV testing followed by VIA triage for CIN-2+ detection was compared with Hybrid Capture 2 viral loads triage, measured in relative light units/cutoff. CIN-2+ prevalence was 1.0%. Corrected sensitivity, false negative rate, and specificity for CIN-2+, respectively, for primary HPV testing were 89.7%, 10.3%, and 83.3%; 44.8%, 55.2%, and 92·3% for VIA; 93.1%, 6.9%, and 80.2% for HPV-VIA cotesting; and 41.4%, 58.6, and 95.4% for HPV with VIA triage scenarios. Using relative light units/cutoff of 5 or greater to triage HPV-positive women had twice the sensitivity as VIA triage, with comparable specificity for CIN-2+. When VIA performs relatively poorly and HPV testing is available, adding VIA to sequential (ie, HPV followed by VIA triage) or primary (HPV-VIA cotesting) screening does not significantly improve CIN-2+ detection beyond primary HPV screening alone. Sequential screening (ie, HPV followed by VIA triage) reduces sensitivity too low for population-based screening programs. The HPV viral loads could offer an alternative low-resource country triage strategy.

Clinical validation of the Cervista® high-risk human papillomavirus test in Chinese women from Fujian province: a cross-sectional study.

PurposeTo estimate the high-risk human papillomavirus (HR-HPV) prevalence in a hospital-based population using the Cervista® and to determine the clinical value and significance of Cervista for cervical cancer screening in Fujian Province, China.Patients and methodsIn a hospital-based population, a total of 10,771 women from the Fujian Province were screened for cervical cancer and precancerous lesions using the thinprep cytologic test (TCT) and/or the Cervista. Women with HR-HPV infection and/or abnormal TCT were referred for colposcopy and biopsy. Pathological diagnosis was used as the gold standard.ResultsThe overall HR-HPV prevalence was 16.57%. Among 10,229 cases, 976 had abnormal cytology results, of which, the HR-HPV positivity rate was 60.35% in this opportunistic screening population. The most common HR-HPV infection style was a simple infection. The most common species was A9 which was also the most prevalent species in all age. The women with CIN2+ (high-grade squamous intraepithelial lesion [HSIL]), especially cancer, were mostly concentrated in the age from 51 to 60 years old. The peak of CIN1 (low-grade squamous intraepithelial lesion, LSIL) prevalence was in the women aged 31–40. When using CIN1+, CIN2+ and CIN3+ as observed endpoints, the sensitivities were 86.07%, 92.73%, and 93.30% and negative likelihood ratio (NPV) were 99.15%, 99.75% and 99.83%, respectively. Cervista and TCT co-testing achieved the highest sensitivity and the lowest NLR.ConclusionThe Cervista could be easily introduced in clinical practice in combination with TCT for cervical cancer screening in China. Patients with species A9 infection require a more actively clinical intervention.