[Global guidelines for cervical cancer and precancerous lesions treatment: a systematic review].

Objective: To systematically summarize current status and recommendations of the global cervical cancer and precancerous lesions treatment guidelines. Methods: The retrieval for all the Chinese and English literature published before July 8, 2021 was conducted in PubMed, Embase, SinoMed Database, CNKI and Wanfang Database, supplemented by a search of health websites of countries worldwide, with"uterine cervical neoplasms""cervix cancer""cervical neoplasm""cervical precancerous lesions""treat*""guideline*""practice guideline*""consensus" "recommendation*""guidebook*"in English as well as"cervical precancerous lesions""cervical neoplasm""treatment""guideline*""consensus"in Chinese as search keywords. A total of 38 guidelines were included for data extraction and analysis. Results: Guidelines covered Asia, Europe, North America, South America and Oceania. Conservative observation was recommended for the CIN1 population. For the women with CIN2/CIN3, ablation or excision was recommended according to the specific situation and guidelines of developed countries give priority to the latter. In low and middle resource countries, given the availability of medical resources, ablative treatment was recommended as an alternative to excisional treatment if the women were eligible. For women with adenocarcinoma in situ (AIS), cervical conization or total hysterectomy was recommended depending on the patient's desire of fertility. For patients with cervical cancer, most guidelines recommended surgery for early disease and smaller lesions, otherwise concurrent chemoradiotherapy was usually the main treatment modality for advanced cancers. All guidelines recommended long-term follow-up to monitor disease recurrence after treatment. Follow-up methods included human papillomavirus (HPV) testing and/or cytology or colposcopy. Most guidelines recommended follow-up at 6 or 12 months after treatment for cervical precancerous lesions, and 3~4 months for cervical cancer. Conclusions: There are some differences in the treatment and management recommendations for cervical cancer and precancerous lesions issued by different countries and regions around the world. Based on the global treatment guidelines and medical resource of different regions, the treatment and management guidelines for cervical cancer and precancerous lesions suitable for different regions of China should be developed, so as to achieve effective treatment.

[Performance of point-of-care testing for cervical cancer screening].

Objective: To evaluate the performance of point-of-care testing for cervical cancer and precancerous lesions screening. Methods: In September 2020, 197 and 273 women were selected by using simple random sampling method from "self-sampling" cohort and "physician-sampling" cohort established in Xiangyuan county, Shanxi Province, China, respectively. Cervical exfoliated cells were collected by women themselves or gynecologists. All samples were detected by POCT and women with positive result were directly referred for colposcopy. Subsequently, all the samples were detected by careHPV and PCR test. Colposcopy and punch biopsy were performed for women with POCT negative but careHPV or PCR test positive at another visit. Using histopathological diagnosis as the gold standard, we calculated sensitivity, specificity and drew the receiver operating characteristic (ROC) curves. The accuracy of POCT was analyzed and compared to that of careHPV and conventional PCR test in cervical cancer and precancerous lesions screening. Results: The median (Q1 , Q3) age of 470 women was 51 (45, 57) years old. Based on self-sampling, the sensitivity and specificity of POCT for CIN2+ were 100.00% (95%CI: 56.56%-100.00%) and 28.95% (95%CI: 22.97%-35.76%), respectively. Compared with POCT, POCT HPV16/18 test had similar sensitivity and higher specificity of 89.47% (95%CI: 84.30%-93.08%). Self-sampling POCT HPV16/18 test had an AUC of 0.947 (95%CI:0.910-0.985), which was higher than that of careHPV and PCR test. Physician-sampling POCT test had 100.00% sensitivity (95%CI: 64.57%-100.00%) and 55.85% specificity (95%CI: 49.83%-61.70%) for detecting CIN2+. POCT HPV16/18 test had lower sensitivity (71.43%, 95%CI: 35.90%-91.76%) and higher specificity (92.45%, 95%CI: 88.63%-95.06%). POCT HPV16/18 test generally showed similar AUC on both self-collected samples and clinician-collected samples (0.947 vs 0.819, P=0.217). Conclusion: POCT HPV16/18 test is an effective method with relatively high sensitivity and specificity for cervical cancer screening.

[Acceptance evaluation of urine self-sampling, vaginal self-sampling and physician sampling in cervical cancer screening].

Objective: To compare the acceptance of urine self-sampling, vaginal self-sampling and physician sampling in cervical cancer screening. Methods: Questionnaire surveys were conducted in women attending cervical cancer screening in Xiangyuan County and Yangcheng County in Shanxi Province from July to November 2015 and from October to December 2018. Both surveys included the following three parts: feelings and acceptance of women in urine self-sampling, vaginal self-sampling and physician sampling, and the ease evaluation of two self-samplings. Results: There were 3 485 questionnaires were collected finally. The proportions of women felt embarrassed in urine self-sampling, vaginal self-sampling and physician sampling were 2.3% (81/3 472), 7.1% (247/3 472) and 8.6% (299/3 472), and 1.3% (46/3 472), 9.7%(3 37/3 472) and 14.9% (518/3 472) of women felt uncomfortable, and 1.0% (35/3 469), 8.5% (295/3 469) and 15.3% (531/3 469) felt pain, and 98.3% (3 334/3 393), 96.3% (3 267/3 393) and 99.0% (3 360/3 393) thought that the sampling were conducted properly (P<0.05). Based on the feeling during sample collection, 61.2% (1 876/3 064), 39.1% (1 199/3 064) and 66.5% (2 037/3 064) women were willing to use the corresponded sampling methods in cervical cancer screening, respectively (P<0.05). If the accuracy was the same, there were 31.8% (1 109/3 485) women preferred self-sampling and 68.2% (2 376/3 485) preferred physician sampling for cervical cancer screening. Meanwhile, 23.5% (820/3 482) preferred vaginal self-sampling in comparison with 76.5% (2 662/3 482) for urine self-sampling in cervical cancer screening. 86.5% (3 007/3 478) of the women thought urine self-sampling was very easy, comparing 40.9% (1 423/3 478) for vaginal self-sampling. Conclusions: The bad feeling of women during urine self-sampling is less common and less serious than those during physician sampling and vaginal self-sampling, and the acceptance for physician sampling is highest, following by urine self-sampling and vaginal self-sampling. Urine self-sampling is much easier than vaginal self-sampling.

[Accelerating the elimination of cervical cancer in China and building a paradigm for "Healthy China" cancer prevention].

Cervical cancer is a common malignant tumor that seriously threatens the health of Chinese women. The situation of prevention and control is still serious. In the past decade, the Chinese government has made great efforts to cervical cancer prevention and control and achieved remarkably in HPV vaccine development, sound health screening system, and treatment capacity of early cervical cancer and precancerous lesions. However, due to the large population base, unequal allocation of health resources, and uneven service quality across regions, there is still a significant gap to achieve the WHO's goal of eliminating cervical cancer by 2030. In order to fulfill the Global Strategy to accelerate the elimination of cervical cancer, China urgently needs to learn from the international experience, combined with the real situation of cervical cancer prevention and control and the latest research progress in China and to put forward appropriate action recommendations and implementation approaches, which will contribute to promote the cervical cancer elimination process and to build a paradigm for "Healthy China" cancer prevention.

[Global guidelines for cervical cancer screening: a systematic review].

Objective: To systematically summarize and evaluate the current cervical cancer screening guidelines worldwide. Methods: "Cervical cancer/cervical intraepithelial neoplasia", "screening", and "guidelines/recommendations" were searched as keywords in PubMed, Embase, China National Knowledge Infrastructure (CNKI), Wanfang Data for cervical cancer screening guidelines. The language was limited to Chinese and English. A total of 29 guidelines were included before September 1, 2020. The basic information and recommendations of the guidelines issued were summarized. Results: Among the 29 cervical cancer screening guidelines, most guidelines targeted on the population aged 25-65 years. Cytology and human papillomavirus (HPV) testing are two commonly used methods for the cervical cancer screening, and HPV testing is increasingly recommended as the primary screening methods. Most guidelines recommended five years interval for the HPV testing-based screening or co-testing (HPV testing and cytology) based screening and three years for the cytology-based. For managing population with abnormal cervical cancer screening, triage or screening repeatedly to identify high-risk populations were more recommended. Direct colposcopy or treatment were allowed for women with higher risk of cervical intraepithelial neoplasia (CIN) during the screening procedure. Several guidelines involving HPV vaccination population recommended them the same strategy as the general population without vaccination. Conclusion: Currently, most of the cervical cancer screening guidelines applied to the population with the average risk of the CINs and were issued by the developed countries. Primary methods for the cervical cancer screening have gradually changed from the cytology to the HPV testing. There is a lack of recommendations targeting special population on cervical cancer screening in the current guidelines.

[Interpretation of "WHO guideline for screening and treatment of cervical pre-cancer lesions for cervical cancer prevention， second edition"].

Cervical cancer can be eliminated through primary, secondary, and tertiary prevention. Yet it remains one of the gravest threats to women's lives worldwide. In November 2020, the World Health Organization (WHO) officially launched the global strategy to accelerate the elimination of cervical cancer, and underlined that screening and treatment for cervical pre-cancer lesions are two of three key measures for the elimination. In July 2021, WHO issued the second edition of"WHO guideline for screening and treatment of cervical pre-cancer lesions for cervical cancer prevention"to provide important guidance to countries to support them in achieving the target of cervical cancer elimination in all women. This article will interpret the methods for the guideline development, the recommendations/good practice statements on screening and treatment to prevent cervical cancer (including the age to start/stop screening, screening methods, screening interval, the management of screen-positive women and treatment of the precancerous lesions, etc.) and its impact globally, providing reference for the updates of guideline and policy making on cervical cancer prevention and control in China.

[Meta-analysis of annual probability of outcome for different cervical disease states].

Objective: To explore the annual probabilities of outcomes for different cervical disease states. Methods: Cohort studies related to the natural history of cervical cancer were retrieved from PubMed, Embase and China Biomedical Literature Database, and the retrieval time was from the establishment of the database to May 2020. Newcastle-Ottawa scale was used to evaluate the quality of the included literatures. The annual outcome probabilities of different cervical disease states in high-risk human papillomavirus (hrHPV) positive, negative and cervical intraepithelial neoplasia grade 1 (CIN1) population were calculated (95%CI). Random-effects model was used for meta-analysis. Egger's test was used to evaluate publication bias; sensitivity analysis was used to evaluate the robustness of the combined parameters. Meta-regression was used to explore factors associated with the heterogeneity of annual outcome probability. Results: A total of 37 studies were included, including 12, 20 and 15 studies involving hrHPV negative, hrHPV positive and CIN1 population, respectively, with a Newcastle -Ottawa scale (NOS) score of 7.05±1.20. The annual probability (95%CI) of progression to CIN1, CIN2 and CIN3+ in hrHPV-positive population were 0.022 2 (0.014 3, 0.031 0), 0.017 0 (0.012 0, 0.022 0) and 0.016 2 (0.012 6, 0.019 8), respectively. The annual probability (95%CI) of progression to CIN1, CIN2 and CIN3+ in hrHPV-negative population was 0.002 7 (0.000 9, 0.004 6), 0.000 7 (0.000 3, 0.001 1) and 0.000 6 (0.000 3, 0.000 9), respectively. The annual probability (95%CI) of reversal to normal, maintenance of CIN1 status and progression to cervical intraepithelial neoplasia grade 2 or above (CIN2+) in CIN1 population were 0.578 1 (0.369 9, 0.786 3), 0.400 1 (0.167 4, 0.632 9), 0.056 9 (0.034 9, 0.078 9), respectively. Egger's test showed that there was publication bias in the annual outcome probability of hrHPV positive progression to CIN2 and CIN3+ and hrHPV negative progression to CIN2 and CIN1 progression to CIN2+, with t values of 5.50, 2.36, 2.80 and 4.12, respectively (all P values<0.05). Sensitivity analysis showed that when excluding any of the studies, the range of annual probability of progression to CIN1, CIN2 and CIN3+ were 0.016 6-0.024 7, 0.014 9-0.018 9 and 0.013 6-0.017 7 among hrHPV-positive population; 0.002 4-0.003 5, 0.000 6-0.000 9 and 0.000 5-0.000 7 among hrHPV-negative population and the range of annual probability of CIN1 reversal to normal, maintenance as CIN1 and progression to CIN2+ were 0.531 8-0.631 2, 0.321 9-0.443 3, and 0.052 0-0.061 0, respectively. Meta-regression analysis showed that region, population origin, population cytological diagnosis, follow-up time, and NOS score were not associated with the heterogeneity of annual outcome probability (all P values>0.05). Conclusion: The annual outcome probability of different cervical disease states in hrHPV positive population is high, and the CIN1 population only needs close follow-up.

[Global development of human papillomavirus vaccination guidelines: a systematic review].

Objective: To systematically summarize the development of global human papillomavirus (HPV) vaccination guidelines. Methods: The retrieval for all the Chinese and English literature published before August 2020 was conducted in PubMed, Embase and China Biomedical Literature Database, with "papillomavirus vaccines" "wart virus vaccine" "guideline" "practice guideline" "health planning guidelines" "guidelines as topic" "practice guidelines as topic" "immunization programs" in English as well as "papillomavirus vaccines" "HPV vaccine" "guideline" "recommendation" "consensus" in Chinese as search keywords. A total of 18 guidelines were included for data extraction and analysis. Results: The 18 pieces of guidelines included 1 pieces of World Health Organization (WHO) position paper, 6 pieces of guidelines at national or provincial level and other 11 pieces of by academic institutions. In national or provincial guidelines, the recommendation for routine vaccination mainly focused on 11-13 year-old adolescents and the recommendation for catch-up vaccination extends to 17-26 years old. Recommendation of guidelines by academic institutions were similar to the WHO position paper: girls aged 9-14 as the primary target for the routine vaccination; females aged 15-26 years old as the secondary target populations when it's feasible, affordable and cost-effective; women aged over 26 could be vaccinated at an individual level. There were only three guidelines simultaneously updated with the national immunization programme and covered four aspects: the vaccinated population (girls-only to gender-neutral vaccination), the periodic catch-up immunization, the dose schedule updates and the change of vaccine types. Conclusions: It's recommended that the development of Chinese HPV vaccination guidelines refer to global guidelines and updates and take full consideration of the epidemiological evidence, resources and current status of the immunization system in China.

[Effectiveness of the thermal ablation in the treatment of human papillomavirus infection and cervical intraepithelial neoplasia in Chinese women].

Objective: To evaluate the effectiveness of thermal ablation in the treatment of human papillomavirus (HPV) infection and cervical intraepithelial neoplasia (CIN) in Chinese women. Methods: The high-risk HPV-positive women aged 20-65 who were detected through a cervical cancer screening project implemented in three rural sites (Etuoke counties in Inner Mongolia, Xiangyuan and Yangcheng counties in Shanxi Province) and one urban site (Shenzhen) in China were included in this prospective study. Follow up evaluation was performed on HPV positive women who underwent thermal ablation (n=166) as well as received no treatment (n=2 716) in cervical cancer screening program. For women with thermal ablation treatment, HPV test and cytology were used for follow-up with the interval of 6 months or longer after treatment. For women without treatment, HPV test was used for annual follow-up. Women with positive results in either of the HPV tests or abnormal cytology were referred for a colposcopy or biopsy if necessary. The HPV clearance rate and the cure rate of CIN were compared between the two groups. Results: A total of 152 women treated with thermal ablation and 2 539 women without treatment reported for follow-up evaluation with the age M(Q1, Q3) of 42 (36, 48) and 47 (41, 54) years old, and the median time to follow-up time of 23.4 (12.4, 24.5) and 23.5 (12.4, 24.0)months, respectively. The HPV clearance rate in women undergoing thermal ablation was significantly higher than that in women with no treatment (73.0% vs 46.1%, P<0.001). The HPV16, HPV52 and HPV58 clearance rates among women receiving thermal ablation were higher than that in women without treatment with the OR (95%CI) of 2.8 (1.3-6.1), 3.2 (1.3-7.9) and 5.8 (2.1-15.6). For women with histologically confirmed CIN at baseline, cure rates were 77.4%(n=72) for thermal ablation. Cure rates of the thermal ablation were 81.0%(n=47) for CIN grade one (CIN1) and 71.4% (n=25) for CIN grade two or worse (CIN2+). Conclusions: Thermal ablation is effective to clear the HPV infection as well as to treat CIN. Particularly for the HPV genotypes with the paramount attributable proportion to cervical cancer and precancerous in China, the HPV clearance rate was significantly higher than that reported in the women without treatment.

[Cost-effectiveness analysis of cervical cancer screening strategies in urban China].

Objective: To explore the most economically feasible cervical cancer screening strategies in urban China. Methods: A series of Markov models were constructed to evaluate health and economic outcomes of different screening strategies. There were 24 screening strategies including four screening methods: liquid-based cytology (LBC), human papillomavirus (HPV) DNA genotyping, HPV DNA genotyping with LBC triage (HPV DNA+ LBC), HPV DNA genotyping and LBC co-testing (HPV DNA-LBC), along with three intervals (every 1, 3 or 5 years) and two starting age for screening (30 or 35 years old) were compared. Models parameters were obtained from a cervical cancer screening study in urban China and literature reviews. Results: The cumulative incidence and mortality risk of cervical cancer declined over 69% and 82% respectively for each screening strategy as compared with the no screening scenario. LBC every five years starting from 35 years old strategy cost the least (RMB 690 per capita) and could save life years compared with no screening. The cost effectiveness ratios of 24 strategies ranged from -10 903 to 117 992 RMB per life year saved. All strategies were cost-effective compared to no screening. In the incremental cost-effectiveness analysis, LBC every 5 years starting from 30 strategy, HPV DNA genotyping every 3 years starting from 30 strategy, LBC every 3 years starting from 30 strategy and LBC every year starting from 30 strategy were dominant strategies. Conclusions: Screening can effectively prevent cervical cancer. In urban Chinese areas with insufficient socioeconomic resources, LBC every 5 years from 35 years old strategy is recommended. In relatively more affluent areas, LBC every 5 years from 30 years old strategy, LBC every 3 years from 30 years old strategy, HPV DNA genotyping every 3 years from 30 years old strategy, and LBC every year from 30 years old strategy are recommended successively.

[Economic evaluation of fifteen cervical cancer screening strategies in rural China].

Objective: To evaluate the feasible cervical cancer screening strategies in rural China. Methods: The study was based on the health industry scientific research project of National Health Commission in 2015, cervical cancer screening technology and demonstration research suitable for rural areas in China, we collected health economics and epidemiological parameters and established the unscreening model and screening model with Treeage Pro 2011 software. Combining with the data acquired from site investigation, including population screening, treatment-related clinical materials and cost data, we simulated the occurrence and the development of cervical cancer of rural women in China under different screening and intervention programs and predicted the screening effects [cumulative incidence, cumulative risk of disease, life years and quality adjusted life years (QALY) , gains] and costs after 20 years, and using health economic evaluation analysis (cost-effectiveness analysis, cost-utility analysis, cost-benefit analysis). Screening programs included five screening strategies [visual inspection with acetic acid/lugol's iodine (VIA/VILI), careHPV, ThinPrep cytology test (TCT), careHPV+TCT, careHPV+VIA/VILI] and three screening intervals (1-year, 3-year, 5-year), a total of fifteen screening programs. Results: Compared with no screening, fifteen screening programs reduced the cumulative incidence by 22.65%-51.76%. Compared with TCT or VIA/VILI, for the same screening interval, the reduced cumulative incidence, the amounts of life-year saved and QALY and benefits gained of careHPV were the highest. The cost-effectiveness ratios of these screening programs ranged (0.44-3.24)×10(4) Yuan per life-year saved, cost-utility ratios ranged (0.15- 1.01)×10(4) Yuan per QALY, benefit-cost ratios ranged 7.73-59.10. The results of incremental costeffectiveness ratios showed that VIA/VILI every five years, VIA/VILI every three years, careHPV every five years, careHPV every three years and careHPV every year were dominant programs. Conclusions: VIA/VILI screening is cost-effective, careHPV is slightly more expensive but more effective. In rural China, careHPV screening every five years could be recommended. This study provides a basis for the determination of cervical cancer screening methods feasible for rural areas in China.

[Prophylactic human papilloma virus vaccines launch the era of comprehensive cervical cancer control].

The etiology of cervical cancer has been fully demonstrated. Different screening strategies are available for different areas with various level of development. The prophylactic human papilloma virus (HPV) vaccine has launched the era of comprehensive cervical cancer control, which is the milestone in the history of human fighting against cancer. However, cervical cancer is still a major public health issue in the world, especially in developing countries. The main challenge lies in the improvement for the coverage of cervical cancer screening and HPV vaccination. Especially for China with large population, various level of the economic development, and the HPV vaccine later than the world for ten years, how to improve the coverage of cervical cancer screening and HPV vaccination? There is a long way to go for the elimination of cervical cancer.

[Research progression of prophylactic HPV vaccine application].

Prophylactic HPV vaccine was a milestone in the prevention and control of HPV-related diseases, especially cervical cancer. The first HPV vaccine has been marketed in the world for more than 10 years. The follow-up study of HPV vaccine clinical trials further confirms the effectiveness and safety. Since HPV vaccine had been introduced into more and more national immunization programs, the population-level effectiveness of HPV vaccine was increasingly proved: Reduced the incidence of HPV infection, genital warts and high-grade precancerous lesions, and improved the herd immunity effect among non-vaccinated populations. However, improvement of the coverage of HPV vaccine, especially in low-and-middle income countries, is the major challenge in putting the HPV vaccine into practice.

[Risk stratification of type-specific human papillomavirus for cervical precancers: evidence from a cross-sectional study in Shenzhen].

Objective: To analyze the epidemiological genotype features of human papillomavirus (HPV) in cervical infection and their risks for cervical precancers among women in Shenzhen area. Methods: A total of 2 717 individuals ranging in age from 30~59 years were recruited in 18 community health centers of Shenzhen city from March 1 to June 15, 2015 by a cluster sampling method. The results of genotype of HPV, liquid-based cytology (LBC), colposcopy and pathology were analyzed. The clinical sensitivity and specificity as well as positive (PPV) and negative (NPV) predictive values of the combination of different HPV genotype in screening the cervical intraepithelial neoplasia (CIN) 2 and above were estimated. Results: The HPV infection rate in Shenzhen area was 15.9% (432/2 717). The most common HPV genotype was HPV52 (22.9%), followed by HPV16 (12.7%), HPV53 (10.0%), HPV51 (8.6%) and HPV58 (8.1%). Compared with HPV16/18 genotyping, HPV33/16 genotyping had a higher sensitivity (57.1% vs. 42.9%, P<0.05) and an analogous specificity (87.3% vs. 86.9%, P>0.05) in predicting CIN2+ . The sensitivity of combination of HPV33/16 genotyping and low grade squamous intraepithelial lesion (LSIL) positive tested by LBC in predicting CIN2+ was 75.0%, significantly higher than 64.3% of atypical squamous cells of undetermined significance (ASC-US) positive tested by LBC alone (P<0.05). The specificities of these two methods mentioned above in predicting CIN2+ were 83.5% and 89.2%, respectively, without statistical difference (P>0.05). Conclusions: Women infected by HPV have distinct risks for CIN2+ according to different high-risk HPV genotypes. The top five risks were HPV 33, 16, 58, 56, and 68. HPV-positive women triaged by LBC LSIL+ combined with HPV33/16 genotyping may be a potential strategy for cervical cancer screening in developed urban area.

[Research progress of HPV therapeutic vaccine].

Bivalent and quadrivalent HPV vaccine have been approved by CFDA successively in China. However, currently available prophylactic vaccines have no therapeutic effect for established infection or disease. In recent years, based on the application of genomics and proteomics for interpretation of tumor antigen, animal experiments and clinical trials of vaccines aiming at a wide variety of antigens have been conducted. In this review, we summarize about the preclinical and clinical research status of HPV therapeutic vaccine and find that the efficacy of HPV therapeutic vaccine alone or combined with other conventional cancer treatment is satisfying, which has potential clinical application value. As the further research of tumor immune regulation and optimization of strategies for the HPV therapeutic vaccine, the vaccine will play an important role in improving the quality of life in cancer patients and eventually become widely used in clinical practice.

[Comparison of screening performance between primary high-risk HPV screening and high-risk HPV screening plus liquid-based cytology cotesting in diagnosis of cervical precancerous or cancerous lesions].

Objective: To evaluate and compare the screening performance of primary high-risk HPV(HR-HPV) screening and HR-HPV screening plus liquid-based cytology (LBC) cotesting in diagnosis of cervical cancer and precancerous lesions (CIN2+). Methods: We pooled 17 population-based cross-sectional studies which were conducted across China from 1999 to 2008. After obtaining informed consent, all women received liquid-based cytology(LBC)testing, HR-HPV DNA testing. Totally 28 777 women with complete LBC, HPV and biopsy results were included in the final analysis. Screening performance of primary HR-HPV DNA screening and HPV screening plus LBC co-testing in diagnosis of CIN2+ were calculated and compared among different age groups. Results: Among the whole population, the detection rates of primary HR-HPV screening and HR-HPV screening plus LBC co-testing are 3.05% (879 CIN2+) and 3.13%(900 CIN2+), respectively. The sensitivity were 96.4% and 98.7% (χ(2)=19.00, P<0.001), and the specificity were 86.2% and 78.8% (χ(2)=2 067.00, P<0.001), respectively. Areas under the receiver operating characteristic (ROC) curve (AUC) showed that the primary HR-HPV screening performed better than co-testing (AUC were 0.913 and 0.888; Z=6.16, P<0.001). Compared with primary HR-HPV screening, co-testing showed significantly higher colposcopy referral rates (16.5% and 23.6%, respectively, χ(2)=132.00, P<0.001) and the number of colposcopy examination for detecting per CIN2+ (5.4 and 7.6, respectively).In the group aged 25-29, the colposcopy referral rates was 8.7 (10.9%(199 cases) vs 1.3%(23 cases)) times as much as the detection rate of primary HR-HPV screening in diagnosis of CIN2+, and was 12.5 (15.7%(288 cases) vs 1.3%(23 cases)) times as much as the detection rate of HR-HPV screening plus cytology contesting. Conclusion: Compared with primary HR-HPV screening, HR-HPV screening plus cytology co-testing does not show better results in the screening performance for CIN2+ detection, and the cost-effectiveness is not good enough, especially in younger age group.

[Role of HPV viral loads in random biopsy under normal colposcopy].

Objective: To explore the role of HPV viral loads in random biopsy under normal colposcopy. Methods: 908 atypical squamous cells of undetermined significance (ASC-US) and HPV positive women, recruited in cluster sampling in 9 provinces including 5 urban areas and 9 rural areas in China from 1999 to 2008 and meeting the inclusion and exclusion criteria were included in this analysis. According to relative light units/cutoff (RLU/CO) value, subjects were stratified as low (286 cases), intermediate (311 cases) and high (311 cases) viral load groups. Risks of cervical intraepithelial neoplasia grade 3 or worse (CIN3+) among different viral load groups were compared with linear trend Chi-square test. Results: Detection rate of CIN3+ in low, intermediate and high viral load groups were 2.1% (6 cases), 2.6% (8 cases) and 6.8% (21 cases) (Chi-square test for trend χ(2)=8.91, P=0.003) and were 60.3, 74.0 and 201.3 times higher than ASC-US and HPV negative women, respectively. Among 908 subjects, 27.0% (245 cases) were abnormal under colposcopy and 68.6% (623 cases) diagnosed as normal. Under normal colposcopy, detection rate of CIN3+ in low, intermediate and high viral load groups were 0.9% (2 cases), 0.9% (2 cases) and 3.8% (7 cases) (χ(2)=6.42, P=0.040). Conclusion: HPV viral loads display satisfactory risk stratification ability among ASC-US and HPV positive women under normal colposcopy. Women with high HPV viral loads show a significantly increased detection rate of existing CIN3+ and could be recommended to perform random biopsy for histologic diagnosis.

[Study on direct economic burden and influencing factors in patients with cervical cancer and precancerous lesions].

Objective: To account the direct cost of uterine cervix carcinoma treatment in China and to explore the related factors which influence the direct financial burden of the disease. Methods: Data was collected through the medical record system and telephone interviews in 14 county-level hospitals and 9 provincial and municipal hospitals from 14 provinces/municipalities enrolled in the Chinese National Health Industry Research Project in 2015. The direct financial burden of uterine cervix carcinoma treatment consisted of the direct medical cost and the direct non-medical cost of treatment in different pathological cervical cancer stages and precancerous lesions. Multiple liner regression method was used to analyze the factors affecting the costs. Results: The age of the 3 246 patients was (46.40±10.43) years, including 2 423 patients from provincial and municipal hospitals and 823 patients from county-level hospitals. The direct financial burden for one patient of pathological uterine cervix carcinoma stage or precancerous lesion ranged from 10 156.3 yuan to 75 716.4 yuan in provincial and municipal hospitals, and for patients from county-level hospitals, the cost was between 4 927.9 yuan and 47 524.8 yuan per person. There was a wide gap between the direct financial burden of patients in different disease stages. The direct financial burden of patients with precancerous lesions ranged from 4 927.9 yuan per person to 11 243.0 yuan per person, as for patients of pathological uterine cervix carcinoma stages, the direct financial burden was between 29 274.6 yuan and 75 716.4 yuan per person. The factors which influence direct financial burden would include: the levels of the hospital, pathological period, medicare reimbursement, days of treatment, and the methods of treatment (P<0.001). Conclusion: The direct financial burden of diseases in patients with pathological uterine cervix carcinoma stage or precancerous lesion differed in different levels of hospital and pathological periods. In addition, medicare reimbursement, days of treatment, and the methods of treatment all had impact on it.

[Distribution and associated factors of high-risk HPV genotypes infection among HPV-positive women who participated cervical screening test in Shenzhen, 2014-2016, China].

Objective: To analyze the distribution and associated factors of high-risk genotypes of HPV in cervical infection among women in Shenzhen. Methods: The information on sociodemographic characteristics and HPV genotypes of HPV-positive women who participated cervical screening test from January 2014 to December 2016 was downloaded from Shenzhen Maternity and Child Healthcare Management Information System. According to the pathogenicity, the high-risk HPV genotypes were divided into 15 types including HPV 16, 18, 31, 33, 35, 39, 45, 51, 52, 53, 56, 58, 59, 66 and 68; and there were 6 low-risk genotypes including HPV 6, 11, 42, 43, 44, and 81. Chi-square tests were applied to compare the proportions of high-risk HPV infection among women who had different sociodemographic characteristics. A non-conditional logistic regression model was used to analyze the associated factors for high-risk HPV infection. Results: In total, all HIV positives received HPV genotyping, with an average age of (38.08±9.38) years old. There were 9 979 (93.9%) high-risk and 645 (6.1%) low-risk HPV infections. The proportions of HPV infections for high-risk type in each year were 91.5%, 93.8%, and 95.6%, increasing with the screening years (χ(2)=54.79, P<0.001). Multivariate logistic regression analysis showed that compared with women younger than 25 years old, women in other age groups (at age 26 to 30 years, 31 to 35 years, 36 to 40 years, 41 to 45 years, and 50 years or older) had increased risks of high-risk HPV infection, with OR (95%CI) of 1.67 (1.20-2.31), 1.49 (1.09-2.03), 1.71 (1.23-2.37), 1.65 (1.19-2.31), and 1.84 (1.26-2.67), respectively; compared with the married, single women had a decreased risk of high-risk HPV infection (OR (95%CI): 0.71 (0.50-1.00)); women received HPV testing in 2015 and 2016 showed higher risk of high-risk HPV infection than those in 2014 (OR (95%CI): 1.43 (1.17-1.74) and 2.03 (1.68-2.46)). The 5 most common HPV genotypes were HPV52 (25.1%, 2 670 cases), followed by HPV16 (19.2%, 2 041 cases), HPV58 (13.3%, 1 413 cases), HPV18 (9.9%, 1 048 cases), and HPV51 (9.3%, 993 cases). Conclusion: Age, marital status, and screening year were associated with high-risk HPV infections. Besides HPV16 and HPV18, the prevention and control on HPV infections for HPV52, HPV58, and HPV51 should be prioritized in Shenzhen area.