[Infection of human papillomavirus and head and neck cancer].

High-risk human papillomavirus (HPV)-related cancers consist of cervical cancer, anal cancer, penile cancer, vulvar cancer, vaginal cancer, and head and neck cancer (HNC). Of these, the disease burden of HNC is second only to cervical cancer. HNC mostly originates from malignant lesions of squamous epithelial cells and mainly includes oral cavity cancer, pharyngeal cancer (including nasopharyngeal cancer, oropharyngeal cancer, and hypopharyngeal cancer), and laryngeal cancer. Tobacco use, alcohol abuse, and HPV infection are three primary risk factors. Recently, there is an upward trend of HNC incidence globally, especially in high-income countries. In China, the disease burden and trends of HPV-related HNC are still not clear. A few small sample size and single-center studies suggest a high HPV prevalence and increasing trend in HNC. Methodological differences in HPV testing and regional variabilities still exist among these studies. Among the anatomic sites, oropharyngeal cancer has been shown to be caused by HPV infection, but the association of HPV with other sites is still under debate. In addition, there is a paucity of relevant studies. Here, this review narrates the association between HPV infection and HNC, compares the differences between global and Chinese studies, and then explores the importance of HPV infection in various anatomical sites. The main objective is to highlight the research on HPV-related HNC and promote relevant prevention and treatment programs.

[World Health Organization guidance Ethical and Governance of Artificial Intelligence for health and implications for China].

With the explosive growth of deep learning and big data technology, artificial intelligence has penetrated into various fields of medical and health care, bringing efficient and high-quality health services to patients, but also a series of ethical and social governance issues have emerged. In order to avoid and eliminate the foreseeable ethical risks and governance challenges in the development of medical artificial intelligence, the World Health Organization (WHO) first released the Ethical and Governance of Artificial Intelligence for Health guidance on June 28, 2021, aimed to provide a framework for ethical guidelines on the deployment of artificial intelligence in clinical practice. At present, there are still shortcomings and this paper takes Healthy China 2030 agenda and the WHO guidelines as strategic ideas, and proposes to shape a consensus on the ethics of medical artificial intelligence, establish rules for human subjects and ownership of responsibilities, improve the legal and regulatory system, and determine human decision-making and moral subject status, taking into account the cultivation of interdisciplinary talents' ethical literacy and other Chinese inspirations are expected to promote the development of medical artificial intelligence ethics governance.

[WHO global strategy on digital health and its implications to China].

The World Health Organization (WHO) released the global strategy report on digital health (2020-2025) in Geneva in 2019, which established the priority of the digital health strategy and formulated strategic objectives, guiding principles, action framework and implementation plans to promote the development of global digital health, and to achieve universal health coverage and the health-related sustainable development goals. Despite China's rapid development in the field of digital health, there is still a big gap between the realization of the goal of digital health. Therefore, it is urgent to grasp the major historical opportunity and step into a new era of digital health with the support of digital technology platform.

[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.

[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.

Study on the characteristics and mechanism of pulsed laser cleaning of polyacrylate resin coating on aluminum alloy substrates.

The behavior of paint removal with a pulsed laser has been investigated using an Nd:YAG fiber laser. Experimental and theoretical analyses are conducted to reveal the underlying mechanism of the paint removal. The results show that the depth, radius, and volume of the pit formed by a single pulse become larger with increases in the energy density. The ideal parameters for the complete removal of paint have been achieved. During the paint removal, burning occurred over the surface, and the variation in element content has been attributed to the absorption of laser energy. Under the action of the pulsed laser, there was breakage and rearrangement of chemical bonds such as C-C, C-N, and C-O in the molecular chain of the polyacrylate paint coating. Through these analyses, the paint removal mechanism was shown to be based on chemical bond breakage, combustion, and mechanical action provided by the thermal expansion and plasma shock.

[Performance of human papillomavirus typing test in cervical precancer lesions and cervical cancer screening].

Objective: To evaluate the performance of Hybribio human papillomavirus (HPV) typing test kit for high risk HPV-DNA typing detection in screening of cervical precancer lesions. Methods: A total of 9 914 women were recruited in Henan, Shanxi, and Guangdong provinces from June to July 2017. All women underwent HPV DNA test. The women who diagnosed as HPV positive and cytological examination ≥ atypical squamous cells of undetermined significance (ASCUS) or HPV negative and cytological examination≥low-grade squamous intraepithelial lesions (LSIL) underwent colposcopy biopsy and pathological examination. Using the pathological diagnosis as the gold standard, the sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and 95% confidence interval (CI) of high-risk HPV and HPV16/18 tests were calculated. Results: The mean age of 9 914 subjects was (45.0±9.3) years old. Among them, 1 302 subjects were detected as high risk HPV positive, including 211 of HPV16 positive and 64 of HPV18 positive. According to the pathological gold standard of cervical intraepithelial neoplasia grade 2 (CIN2) or worse, the sensitivity and specificity of high risk-HPV and HPV 16/18 for triaging ASCUS women were 90.6% (95%CI: 75.8%-96.8%) and 78.0% (95%CI: 74.5%-81.2%) as well as 56.3% (95%CI: 39.3%-71.8%) and 95.7% (95%CI: 93.8%-97.1%), respectively. The sensitivity and specificity of high risk-HPV and HPV 16/18 for cervical precancer lesions screening were 95.1% (95%CI: 88.1%-98.1%) and 87.6% (95%CI: 86.9%-88.2%) as well as 65.9% (95%CI: 55.1%-75.2%) and 97.8% (95%CI: 97.5%-98.1%), respectively. Conclusions: The Hybribio HPV test kit has a relative high sensitivity and specificity for cervical precancer lesions screening and ASCUS triaging. It is reliable for HPV DNA detection and cervical cancer screening.

[Performance of high-risk HPV typing test in early diagnosis of cervical cancer].

Objective: To evaluate the performance of High-risk HPV typing detection in cervical cancer screening. Methods: A total of 3 231 women were recruited as the subjects of cervical cancer screening from Jiyuan city of Henan provinces from June to July 2017. All women underwent HPV DNA test. The women with cytological examination ≥ASCUS or cytological examination negative and HPV 16/18 positive underwent colposcopy biopsy and pathological examination. Pathological diagnosis was used as the gold standard. Sensitivity, specificity, positive predictive value (PPV), negative predictive value(NPV) as well as corresponding 95% confidence interval (CI) of HR-HPV and HPV 16/18 were calculated. Results: The mean age of 3 231 subjects selected in this study was 46.84±10.00 (21-64) years old. 524 subjects had the positive results of HR-HPV, including 91 of HPV16 and 15 of HPV18. Pathological test result CIN2+ was the gold standard. The sensitivity and specificity of HR-HPV for cervical precancer lesions screening were 93.75 (95%CI: 79.85-98.27) and 84.56% (95%CI: 83.26-85.77), respectively. To compared with HR-HPV, HPV16/18 had low sensitivity (65.63%, 95%CI: 48.31-79.59)and higher specificity (97.44%, 95%CI: 96.83-97.93). After age stratification by age 30 and 45, the sensitivity of HPV 16/18 was same with HR-HPV (100%, 95%CI: 34.24-100.00), the specificity of HPV 16/18 was higher than HR-HPV (98.71%, 95%CI: 96.27-99.56 vs 84.48%, 95%CI: 79.27-88.58) in<30 age group.The sensitivity of HR-HPVin 30-45 and ≥45 age group were higher than HPV16/18 (85.71%, 95%CI: 48.69-97.43 vs 71.43%, 95%CI: 35.89-91.78, 95.65%, 95%CI: 79.01-99.23 vs 60.87%, 95%CI: 40.79-77.84), but the specificity werelower than HPV16/18 (86.89%, 95%CI: 84.58-88.90 vs 98.51%, 95%CI: 97.51-99.11、83.49%, 95%CI: 81.81-85.04 vs 96.80%, 95%CI: 95.94-97.48). Conclusions: HR-HPV detection has relatively high sensitivity and specificity in cervical cancer screening. For >30 years old women, HR-HPV is more recommended in cervical cancer screening. Therefore, HR-HPV detection is an effective method for cervical cancer screening.

[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.

[A long journey of cervical cancer prevention in China].

Cervical cancer is the fourth most common cancer in women worldwide. More than 80% of cervical cancer deaths occur in low- and middle-income countries. Global health faces enormous challenges. Prevention and control of cervical cancer have a promising prospect, owing to the etiology of carcinogenesis being clearly understood, great efficacy of HPV prophylactic vaccine being proved, technologies of early detection and treatment being well-established, and the various screening strategies being available for communities with different social and economic status. In this commentary, we focused on China and discussed the challenges and opportunities faced by the grass-roots hospitals and clinics, considering the large population load in China and unbalanced allocation of scarce healthcare resources across the nation. In the framework of "Healthy China 2030" , much needs to be done to prevent and control cervical cancer in the upcoming 12 years.

[Application of artificial intelligence in diagnosis of medical endoscope].

Through a brief overview of the origin and development of artificial intelligence, the research progress of artificial intelligence in digestive endoscopy, ophthalmoscopy and electronic colposcopy was summarized, and the importance of its application was clarified. This article induced the main problems and suggestions of artificial intelligence in the development of medical endoscopes, and prospected the future application of artificial intelligence in medical endoscopy diagnosis.

[Real-world research on cervical cancer screening program and effect evaluation for Chinese population].

Objective: To evaluate the actual efficacy of cervical cancer and precancerous lesions screening approaches in real-world regions with different economic levels in China. Methods: The demonstrative application and effect evaluation of cervical cancer screening program were conducted in 21 hospitals nationwide from 2015 to 2018. Multi-stage sampling method was adopted to divide the country into 7 large areas according to geographical location. Two to four screening sites of two types of cancer (cervical cancer and breast cancer) were selected in each area, and the grassroots screening sites were implemented under the guidance of superior hospitals. In rural areas, women were initially screened using cytology, human papillomavirus (HPV) testing and visual inspection. The women with positive cytology or visual inspection were referred for colposcopy, and the women with positive HPV infection were randomly referred for reflex cytology or visual inspection, or direct colposcopy examination. In urban areas, women were primarily randomized into cytology or HPV testing groups. The women with abnormal cytology or positive HPV 16/18 infection were directly referred for colposcopy examination, whereas the women with positive infection of the other 12 high-risk subtypes of HPV were referred for reflex cytology or colposcopy. All of recruited women would be follow-up and screened by the baseline screening techniques in the third year while the positive women underwent colposcopy examination. The positive rates, referral rates, the detection rates of grade 2 and above of cervical intraepithelial neoplasia (CIN 2+ ) were compared. Results: A total of 63 931 women were recruited at the baseline. Among them, 11 rural sites included 33 823 women: 15 577, 11 157 and 7 089 women were screened by HPV testing, visual inspection via acetic acid or Lugol's iodine (VIA/VILI) and cytology, respectively. Additionally, 30 108 women were from 10 urban sites: 9 907 and 20 201 women were screened by cytology and HPV subtyping, respectively. The HPV positive rate for urban women was 9.34%, whereas that for rural women was 12.53%. The abnormal rate of cytology for urban women was 5.63%, and that for rural women was 4.24%. The positive rate of VIA/VILI in the rural women was 12.25% Furthermore, the detection rate of CIN2+ at the baseline was 0.56%, and that was statistically higher in HPV-positive group than cytology-positive group (P<0.05). Conclusions: All of screening sites completed the baseline screening tasks as expected. The prevalence of HPV infection is higher in rural women than urban women. The performance of HPV testing is better than cytology for detecting CIN2+ cases. This real-world demonstration study provides evidences for cervical cancer prevention and control in different regions.

[Performance of combined liquid based cytology and HPV nucleic acid test for detecting cervical precancer among women attending screening].

Objective: To evaluate the clinical performance of HPV genotyping with cytology for detecting cervical precancer among women attending co-testing. Methods: A total of 2 883 females who participated in cervical cancer screening program were recruited from Erdos in 2016. All the participants were tested by cytology and HPV genotyping. In 2017, women with abnormal cytology results or HPV positive were followed up. Pathological cervical intraepithelial neoplasia (CIN) 2+ was the study end-point. Clinical performance indexes were calculated, including sensitivity, specificity, positive predictive value, negative predictive value, referral rate and missed cases. Results: INNO-LiPA resulted in a detection rate of 18.87%(544/2 883) for the 14-type high risk HPV. HPV16 was the most common infectious genotype (4.06%), followed by HPV52 (3.61%), HPV51 (2.50%), HPV58 (1.98%), and HPV18 (1.56%). With more HPV genotypes added into the group, sensitivity increased and the specificity decreased. Addition of HPV16, 58, 33, 39, 52, 18, 31 for detection lead to the maximun value of area under the curve (AUC)=0.913 (95%CI: 0.882-0.944). Compared with traditional screening method by cytology, cotesting decreased the number of missed diagnosis. Meanwhile, the fifth method (co-testing: triage of women with HPV16/18+ , cytological minor abnormalities and HPV58, 33, 39, 52, 31+ or cytological high grade abnormalities) did not increase referral rate (8.99% vs. 8.71%, P=0.525), with five cases of missed diagnosis (sensitivity of 92.1% and specificity of 93.2%). Conclusions: Co-testing with triage of women with HPV16/18+ , cytological minor abnormalities and HPV58, 33, 39, 52, 31+ or cytological high grade abnormalities would provide better clinical performance. In co-testing, triage of HPV16/18 was used in women with normal cytology; triage of HPV58, 33, 39, 52 and 31 was used in women with low-grade abnormal cytology; referral colposcopy was used in women with high-grade abnormal cytology, which would provide better clinical performance.

[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.

[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.