Progress of Research on the Relationship between Lung Microbiome and Lung Cancer / 中国肺癌杂志

The microbiota plays an important role in the biological functions of the human body and is associated with various disease states such as inflammation (gastritis, hepatitis) and cancer (stomach, cervical, liver). The Human Microbiome Project painted a panorama of human microorganisms in its first phase, incorporating body parts such as the nasal cavity, oral cavity, intestine, vagina and skin, while the lungs were considered a sterile environment. However, studies in recent years have confirmed the presence of a rich microbial community in the lung, and the association of this lung microbiota with lung disease has become a hot topic of research. Current research has found that patients with lung cancer have a specific microbiota compared to healthy individuals or patients with lung disease. Even in patients with lung cancer, a lung microbiota specific to the tumor site is present. In addition, different pathological types and metastatic status of lung cancer can lead to differences in microbiota. Mechanistic studies have found that the lung microbiota may influence lung cancer development by affecting the immune response. Clinical studies on lung microbiota and immunotherapy are still in the preliminary stage. More relevant studies are needed in the future to provide high-quality evidence to further understand the oncogenic mechanisms of lung microbiota and provide new ideas for clinical treatment. This paper briefly reviews the progress of lung microbiota research in terms of its relevance to lung cancer, possible molecular mechanisms and applications in clinical treatment, and provides an outlook for future research.
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Prophylactic human papilloma virus vaccines launch the era of comprehensive cervical cancer control / 中华预防医学杂志

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.

Cost-effectiveness analysis of cervical cancer screening strategies in urban China / 中华肿瘤杂志

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.

Comparison of high-risk human papillomavirus infection rate and genotype distribution between Han and Mongolian women / 中华流行病学杂志

Objective@#To understand the infection rate and genotype distribution of high risk-human papillomavirus (HR-HPV) and the detection rate of different grades of cervical lesions in Han and Mongolian women in China and provide evidence for the development of screening and vaccination strategies for the prevention and control of cervical cancer in different ethnic groups.@*Methods@#In June 2017, a multicenter, population-based study for cervical cancer screening in low-resource settings in China was conducted in three rural areas: Xiangyuan and Yangcheng counties in Shanxi province, and Etuoke county in Inner Mongolia Autonomous Region. A total of 9 517 women aged 30-65 years were included in the study, and two cervical and vaginal secretion samples were collected from them for HPV and PCR-based HPV DNA tests. The positive samples in any of two tests were used for PCR-based HPV genotyping test by using Sansure-pioneered One-Step Fast Release technology. Women with positive results in any the HPV tests were referred for colposcopy and punch biopsy was given if cervical intraepithelial neoplasia lesion (low-grade lesion or worse) was suspected in colposcopy evaluation. Endocervical curettage was performed if women had an unsatisfactory colposcopy exam (the squamocolumnar junction was not completely visible). Pathological detection result was used as the golden standard of diagnosis.@*Results@#HR-HPV infection rates in Han and Mongolian women were 21.83% (1 842/8 438) and 24.93% (269/1 079), respectively. There were statistical differences in HPV infection rates between the two ethnic groups (χ2=5.328, P=0.021). The detection rate of cervical intraepithelial neoplasia grade 1 in Mongolian women (2.83%) was higher than that in Han women (0.87%), and the difference was statistically significant (χ2=33.509, P<0.001). There were no significant differences in cervical intraepithelial neoplasia grade 2 or worse detection rate between the two ethnic groups [Mongolian woman: 1.04% (11/1 059), Han Woman: 0.95% (80/8 378), χ2=0.069, P=0.793]. Among Han and Mongolian women with cervical intraepithelial neoplasia grade 2 or worse, the three most common HR-HPV types were HPV16, HPV52 and HPV58. There was no significant difference for multiple infection rate between Han and Mongolian women (41.37% vs. 44.35%, χ2=0.764, P=0.382).@*Conclusions@#The results show that HPV infection rate in Mongolian women was higher than that in Han women. Close attention should be paid to HPV16, 52 and 58 in the prevention and control of cervical cancer in Han and Mongolian women.

Economic evaluation of fifteen cervical cancer screening strategies in rural China / 中华妇产科杂志

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)×104 Yuan per life-year saved, cost-utility ratios ranged (0.15-1.01)×104 Yuan per QALY, benefit-cost ratios ranged 7.73-59.10. The results of incremental cost-effectiveness 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.

Economic evaluation of fifteen cervical cancer screening strategies in rural China / 中华妇产科杂志

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)×104 Yuan per life-year saved, cost-utility ratios ranged (0.15- 1.01)×104 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.

Study on direct economic burden and influencing factors in patients with cervical cancer and precancerous lesions / 中华预防医学杂志

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.

Risk stratification of type-specific human papillomavirus for cervical precancers: evidence from a cross-sectional study in Shenzhen / 中华肿瘤杂志

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 progression of prophylactic HPV vaccine application / 中华肿瘤杂志

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.

Research progress of HPV therapeutic vaccine / 中华预防医学杂志

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.

Distribution and associated factors of high-risk HPV genotypes infection among HPV-positive women who participated cervical screening test in Shenzhen, 2014-2016, China / 中华预防医学杂志

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 (χ2=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.

Role of HPV viral loads in random biopsy under normal colposcopy / 中华预防医学杂志

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 χ2=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) (χ2=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.

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 / 中华预防医学杂志

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% (χ2=19.00, P<0.001), and the specificity were 86.2% and 78.8% (χ2=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, χ2=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.

Knowledge and attitudes toward prophylactic human papillomavirus vaccines among the mainland Chinese population / 中国肿瘤临床

To assess knowledge of and attitudes toward prophylactic HPV vaccines among the mainland Chinese population and to determine possible influencing factors in order to provide reference data for policymakers to develop HPV vaccination strate-gies in China. Methods: This large-scale national cross-sectional epidemiological study was conducted from May 2009 to May 2012. The general population, medical personnel, and school students participated in the investigation. Participants’basic information, as well as their knowledge of and attitudes toward HPV vaccines were collected through questionnaires. Chi-square tests and Logistic re-gression were performed for the statistical analysis. Results: A total of 18,677 people responded effectively, with a median age of 32 (ranging from 15 to 79 years). In terms of vaccine awareness, only 24.5% had heard of prophylactic HPV vaccines and 14.1% knew that HPV vaccines can prevent diseases such as cervical cancer. The good news was that 83.5% of respondents were willing to vaccinate themselves, their partners, or their children. People who knew more about vaccines, the rural population, and female participants were more likely to hold positive attitudes toward vaccination (adjusted ORs were 2.81, 2.14, and 1.25, respectively). Those partici-pants who were reluctant to accept HPV vaccination were concerned mainly about the safety of the vaccines (64.7%). Furthermore, 66.3% of the respondents expected the maximum price of the HPV vaccine to be less than 300 RMB. Conclusions: Mainland Chinese people generally know little about HPV vaccines. However, most of them think positively about the vaccinations after learning about them. It is high time for the government to launch HPV and cervical cancer health education or promotional campaigns to eliminate concerns about HPV vaccine safety. Furthermore, discounted or free vaccines are needed.

Multi-center cross-sectional study on type-specific human papillomavirus infection among Chinese women / 中华流行病学杂志

<p><b>OBJECTIVE</b>To study the type-specific prevalence of human papillomavirus (HPV) infection among women in China and to provide evidence for primary prevention and screening of cervical cancer programs.</p><p><b>METHODS</b>From May, 2004 to April, 2007, a population-based multicenter cross-sectional study was conducted by the Cancer Hospital, Chinese Academy of Medical Sciences. Women aged 17-59 years from 4 urban areas and 4 rural areas, were screened, under both liquid based cytological and HPV tests for cervical cancer. Specimens of cervical cell were used for genotyping with Linear Array or enzyme-linked immunesorbent assay. Women showed positive in primary screening were referred to exams for further colposcopy and/or histo-pathological detections.</p><p><b>RESULTS</b>A total of 6723 women were included in the data analysis. The overall prevalence of HPV infection was 15.5%. Two age-specific peaks of prevalence of HPV infection were detected among the different age groups. The first peak occurred in 17-24 year-old women in both rural areas and urban areas, while the second one occurred in 40-44 year-old women in urban areas and in 45-49 year-old women in rural areas. The prevalence of HPV infection increased with the severity of diagnosed cervical intraepithelial lesions by cytological or histo-pathological test (χ(2)=62.857, 22.113, P<0.001). HPV16 (3.2%) was seen the most common high risk HPV type, followed by HPV58 (1.8%) , HPV52 (1.5%) , HPV18 (1.0%) and HPV33 (1.0%) respectively. Other common types would include HPV66 (0.64%) , HPV42 (0.58%) and HPV53 (0.46%). The prevalence of HPV16 infection in rural women was significantly higher than that in urban women (χ(2)=4.696, P< 0.05).</p><p><b>CONCLUSION</b>Prevalence of HPV infection in Chinese women seemed to be high and with two age-specific peaks. HPV16 appeared the most commonly seen type in women with cervical lesions. HPV58 and 18 were the predominant types. Type-specific distribution of HPV infection should be taken into consideration in the development of comprehensive cervical cancer prevention strategies in China.</p>

Value of 4-quadrant biopsies under colposcopy for detecting precancerous lesions in cervical cancer screening / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To evaluate the value of colposcopical 4-quadrant biopsies for detecting precancerous lesion in cervical cancer screening.</p><p><b>METHODS</b>We used the data of a cross-sectional screening study in 1999, in which 1,997 women received cervical cancer screening in Xiang Yuan County, Shanxi province. The sensitivity, specificity and accuracy of both 4-quadrant biopsy and colposcopy directed biopsy to detect high-grade or more severe squamous intraepithelial lesions (HSIL+) were calculated.</p><p><b>RESULTS</b>1,784(89.3%) women who received 4-quadrant biopsies and endocervical curettage were negative. 127(6.4%) women were diagnosed as LSIL, 74(3.7%) women as HSIL and 12(0.6%) cases of squamous cell carcinoma. 1,478(74.0%) women who received biopsies in the sites of abnormal lesions were negative, 463(23.2%) cases of LSIL, 41(2.1%) cases of HSIL, 15(0.8%) cases of squamous cell carcinoma. The positive rate was 26.0%(519/1,997) for colposcopy, and the coincidence rate was 73.7% with pathological diagnosis. Sensitivity and specificity were 81.4% and 76.5% of colposcopy for HSIL+. In total of 519 women were found to be with any abnormal colposcopic appearance. The consistency rate between 4-quadrant biopsies and suspicious lesion-directed biopsies was 96.3%. By suspicious lesion-directed biopsy alone, 14.8% cervical lesions were miss-diagnosed, of which 8.6%(5/58) cases of total HSIL and 24.1%(14/58) cases of all LSIL.</p><p><b>CONCLUSIONS</b>4-quadrant biopsy can detect more HSIL+ lesions and is more accurate than suspicious lesion biopsy alone. As an important triage technique to detect cervical precancerous lesions, it can improve the detection rate of HSIL+ lesions in cervical cancer screening.</p>

Effectiveness of FTA Elute® indicating cartridge in combination with hybrid capture 2 for cervical cancer screening / 中华预防医学杂志

<p><b>OBJECTIVE</b>To evaluate the effectiveness of FTA Elute® Cartridge (GE healthcare, Kent, UK) in combination with hybrid capture 2 (HC2) testing for cervical cancer screening.</p><p><b>METHODS</b>From May to June 2012, 412 women aged 25 to 65 years in Jiangxi Tonggu were enrolled in the study. We used pathological outcome as the gold standard, and the accuracy of the FTA card in combination with HC2 testing was investigated from both physician- and self-sampling, respectively.</p><p><b>RESULTS</b>Physician sampling using the FTA card in combination with HC2 testing showed a comparable sensitivity (12/13) with the liquid based medium, but a higher specificity 69.5% (266/383) vs (77.8%, 298/383) (P < 0.001).When self sampling method was used, the sensitivity and specificity of using the FTA card in combination with HC2 testing with liquid based medium was 10/13 vs 8/13(P = 0.625) and (62.3%, 238/382) vs (75.7%, 289/382) (P < 0.001). The agreement of detection results for HC2 between FTA and liquid-based sampling medium was 86.1% (340/395) and 79.5% (314/395). For physician-collected samples used for HC2 testing to detect CIN2+, the accuracy of the FTA card was superior to that of the liquid-based medium (area under the receiver operating characteristic curve (AUC) = 0.898, 95%CI:0.838-0.958).</p><p><b>CONCLUSION</b>FTA Elute® cartridge in combination with HC2 testing is a promising method of specimen transport for cervical cancer screening programs with a good precision.With further optimization, it could become an effective method for cervical cancer screening in various economic levels of areas.</p>

A prospective study on the prognosis of biopsy-confirmed cervical intraepithelial neoplasia grade 1 and the relationship with high-risk human papillomavirus / 中华预防医学杂志

<p><b>OBJECTIVE</b>To evaluate the prognosis of cervical intraepithelial neoplasia grade 1 (CIN1) at different follow-up time points in Chinese women and the relationship with high-risk human papillomavirus (HR-HPV) infection.</p><p><b>METHODS</b>Biopsy-confirmed CIN1 women were followed up from cervical cancer screening cohorts established during 1999 to 2008 in Xiangyuan county, Yangcheng county, Qinxian county and Wuxiang county, Shanxi Province.In each follow-up visit, participants were examined by visual inspection with acetic acid, liquid-based cytology and HR-HPV DNA testing. Those with any positive results received colposcope and biopsies. The cumulative incidence rates of CIN grade 2 or worse (CIN2+) and CIN grade 3 or worse (CIN3+), regression rates and persistent rates were calculated using pathological findings as a gold standard. The risks of progression related with HR-HPV were evaluated stratified by baseline and follow-up HR-HPV status.</p><p><b>RESULTS</b>A total of 228, 224, 261 and 105 CIN1 women received the 1-year, 2-year, 6-year and 11-year follow-up exams, respectively. The cumulative incidence rate of CIN2+ among baseline HR-HPV positive women was 4.8% (6/126), 10.7% (16/150), 16.9% (29/172) and 35% (19/55) in the above follow-up visits, respectively, and their risk of progression was 2.7(95%CI:0.3-22.0), 2.9 (95%CI:0.7-12.1), 12.0 (95%CI:1.7-86.2) and 30.6 (95%CI:1.9-493.5) times higher than baseline HR-HPV negative women. Moreover, the cumulative incidence of CIN2+ among women with positive HR-HPV both at baseline and follow-up visit was 11% (6/55), 14% (6/42), 17% (10/60) and 50% (13/26) in the above follow-up visits, respectively.No new CIN2+ cases were found among those with negative HR-HPV both at baseline and follow-up visits.</p><p><b>CONCLUSION</b>Given that CIN1 progression is related to HR-HPV infection, different follow-up intervals and strategies for CIN1 should be taken according to HR-HPV infection status.</p>

Value of high risk human papillomavirus viral load in predicting cervical lesions and triaging for high risk (HR)-HPV-positive women / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To evaluate the value of high risk (HR)-HPV viral load in predicting cervical lesions and triaging for HR-HPV positive women.</p><p><b>METHODS</b>The study cohort came from a multicenter cervical cancer screening program. HR-HPV was detected by hybrid capture 2 (HC-2) assay, and viral load was measured by the ratio of relative light units to cut off (RLU/CO). Women were divided into 4 groups according to the RLU/CO value, and CIN diagnostic system was used to describe the severity of cervical lesions. Chi-square trend test was used to analyze the association between viral load and CIN. The absolute and relative risks of CIN2+ in different viral load groups were calculated, and the clinical performance to detect CIN2+ at follow-up by different cut-off values of baseline RLU/CO was also calculated.</p><p><b>RESULTS</b>2 725 women with complete results of both baseline and follow-up were included in this analysis. The severity of cervical lesions increased with the increasing viral load (P < 0.001). In women with normal or CIN1 diagnosis at baseline, the absolute risk of one-year accumulative CIN2+ was 0.11% in the HR-HPV-negative group, compared with 3.14% in the moderate viral load group and 6.09% in the high viral load group, and the relative risk of 29.05 (95%CI: 6.07-138.99) in the moderate viral load group and 56.34 (95%CI: 12.89-246.30) in the high viral load group. Raising cut-off value of baseline HR-HPV viral load to 15.00, RLU/CO decreased the number of women who need to be followed up at one-year from 774 to 412, with the sensitivity of 91.30% and specificity of 47.94% in detecting CIN2+ at follow-up.</p><p><b>CONCLUSIONS</b>The risk of cervical cancer and precancerous lesions increases with the increasing HR-HPV viral load. Raising the cut-off value of HR-HPV viral load can triage for HR-HPV-positive women, therefore help to allocate the health resources more effectively.</p>

Implication of inverse-probability weighting method in the evaluation of diagnostic test with verification bias / 中华流行病学杂志

To evaluate and adjust the verification bias existed in the screening or diagnostic tests.Inverse-probability weighting method was used to adjust the sensitivity and specificity of the diagnostic tests,with an example of cervical cancer screening used to introduce the Compare Tests package in R software which could be implemented.Sensitivity and specificity calculated from the traditional method and maximum likelihood estimation method were compared to the results from Inverse-probability weighting method in the random-sampled example.The true sensitivity and specificity of the HPV self-sampling test were 83.53％ (95％CI:74.23-89.93) and 85.86％ (95％ CI:84.23-87.36).In the analysis of data with randomly missing verification by gold standard,the sensitivity and specificity calculated by traditional method were 90.48％ (95％CI:80.74-95.56) and 71.96％ (95％CI:68.71-75.00),respectively.Thc adjusted sensitivity and specificity under the use of Inverse-probability weighting method were 82.25％ (95％ CI:63.11-92.62) and 85.80％ (95％ CI:85.09-86.47),respectively,whereas they were 80.13 ％ (95％ CI:66.81-93.46) and 85.80％ (95％ CI:84.20-87.41) under the maximum likelihood estimation method.The inverse-probability weighting method could effectively adjust the scnsitivity and specificity of a diagnostic test when verification bias existed,especially when complex sampling appeared.