Objective:To understand the incidence trend and temporal distribution of breast cancer and reproductive system cancers in women in different age groups and areas in China from 2006 to 2017.Methods:Based on the incidences of breast cancer, vulvar cancer, vaginal cancer, cervical cancer, uterine corpus cancer, and ovarian cancer in women, average age at diagnosis and cases in different age groups and areas in China were calculated, standardized through world population. Software Joinpoint 4.5.0.1 was used to calculate average annual percent of change (AAPC).Results:Between 2006 and 2017, the overall age-standardized incidence rate (ASIR) of the six cancers showed an increasing trend from 39.48/100 000 to 51.11/100 000 (AAPC=2.24%, 95% CI: 1.59%-2.89%). The increasing trend was more obvious in rural area (AAPC=4.65%,95% CI:3.67%-5.64%), whereas no significant increase was observed in urban area (AAPC=0.15%,95% CI:-0.26%-0.56%). Except uterine corpus cancer, the incidences of 5 cancers showed increasing trends. The incidences of cervical cancer showed similar upward trends in urban and rural areas. In urban area, the ASIRs of breast cancer, vaginal cancer and vulvar cancer showed no significant increase, while in rural area it showed significant increase. The ASIR of ovarian cancer showed a decreasing trend in urban area and an increasing trend in rural area. The average age at diagnosis increased for all the cancers, except uterine corpus cancer. However, after standardizing through world population, the increases in the standardized average age at diagnosis were observed only in cervical cancer and vaginal cancer from 49.11 and 55.15 years to 52.13 and 58.81 years, respectively. Conclusions:The overall ASIR of breast cancer and reproductive system cancers in women showed increase trend in China in 2006-2017, and the increase trend was more obvious in rural area than in urban area. Meanwhile, the accessibility to medical facilities in rural area needs to be improved to ensure medical care, early diagnosis and early treatment for the purpose of bridging the gap in female cancer incidence between rural area and urban area.

Objective:To evaluate the 10-year protective effect and immunogenicity of quadrivalent human papillomavirus (HPV) vaccine in Chinese women aged 20 to 45 years.Methods:From October 2019 to April 2020, a long-term follow-up study was conducted on the subjects of the Phase III clinical trial of the quadrivalent HPV vaccine (NCT00834106). Participants underwent a questionnaire survey, venous blood sampling, gynecological examination, cervical exfoliated cell pathology examination, and serum neutralizing antibody titers for HPV-6, 11, 16, and 18 were measured using a pseudovirus neutralization assay. The results of the cytological examination and the positive rate and titers of serum antibodies of different cervical exfoliated cells were compared.Results:A total of 889 subjects were followed up, including 240 in the control group, 453 in the vaccination group and 196 in the post-trial vaccination group. The age of the control group was (40±7) years old, which was higher than that of the supplementary vaccination group and the vaccination group [(38±4) and (38±6) years old, respectively] ( P<0.05). There were no statistically significant differences in condom use and sexual frequency among all groups (all P values>0.05). The abnormal proportion of cervical exfoliation cytopathology in the vaccination group was 3.7% (17/453), which was significantly lower than that in the control group [9.6% (23/240)] and post-trial vaccination group [5.6% (11/196)] ( P<0.05). There were two cases of cervical intraepithelial neoplasia (CIN) grade 1 in the vaccination group, two cases of CIN grade 1 and three cases of CIN grade 2 and above in the control group, and no CIN grade 1 and above cases in the post-trial vaccination group. The positive rate of HPV-18 antibody was 35.5% (161/453) in the vaccination group and 76.0% (149/196) in the post-trial vaccination group, which was significantly lower than that of other types ( P<0.05). The neutralizing antibody GMT ratio between the vaccination group and the control group ranged from 2.62 to 25.33 (9.05 to 83.08). Conclusion:Protective neutralizing antibodies are sustained in Chinese women aged 20 to 45 years after ten years of vaccination with quadrivalent HPV vaccine.

Objective:To evaluate the 10-year protective effect and immunogenicity of quadrivalent human papillomavirus (HPV) vaccine in Chinese women aged 20 to 45 years.Methods:From October 2019 to April 2020, a long-term follow-up study was conducted on the subjects of the Phase III clinical trial of the quadrivalent HPV vaccine (NCT00834106). Participants underwent a questionnaire survey, venous blood sampling, gynecological examination, cervical exfoliated cell pathology examination, and serum neutralizing antibody titers for HPV-6, 11, 16, and 18 were measured using a pseudovirus neutralization assay. The results of the cytological examination and the positive rate and titers of serum antibodies of different cervical exfoliated cells were compared.Results:A total of 889 subjects were followed up, including 240 in the control group, 453 in the vaccination group and 196 in the post-trial vaccination group. The age of the control group was (40±7) years old, which was higher than that of the supplementary vaccination group and the vaccination group [(38±4) and (38±6) years old, respectively] ( P<0.05). There were no statistically significant differences in condom use and sexual frequency among all groups (all P values>0.05). The abnormal proportion of cervical exfoliation cytopathology in the vaccination group was 3.7% (17/453), which was significantly lower than that in the control group [9.6% (23/240)] and post-trial vaccination group [5.6% (11/196)] ( P<0.05). There were two cases of cervical intraepithelial neoplasia (CIN) grade 1 in the vaccination group, two cases of CIN grade 1 and three cases of CIN grade 2 and above in the control group, and no CIN grade 1 and above cases in the post-trial vaccination group. The positive rate of HPV-18 antibody was 35.5% (161/453) in the vaccination group and 76.0% (149/196) in the post-trial vaccination group, which was significantly lower than that of other types ( P<0.05). The neutralizing antibody GMT ratio between the vaccination group and the control group ranged from 2.62 to 25.33 (9.05 to 83.08). Conclusion:Protective neutralizing antibodies are sustained in Chinese women aged 20 to 45 years after ten years of vaccination with quadrivalent HPV vaccine.

Objective:To observe and analyze the gene mutation and clinical phenotype of patients with cone and rod dystrophy (CORD).Methods:A pedigree investigarion. Two CORD pedigrees including 2 patients and 6 family members were enrolled in Ningxia Eye Hospital of People' Hospital of Ningxia Hui Automous Region for this study. The patients were from 2 unrelated families, all of whom were probands. Take medical history with best-corrected visual acuity (BCVA), color vision, slit lamp microscopy, indirect ophthalmoscopy, fundus color photography, optical coherence tomography (OCT), autofluorescence (AF), fluorescein fundus angiography (FFA), electroretinogram (ERG). The peripheral venous blood of patients and their parents was collected, whole genome DNA was extracted, Trio whole genome exome sequencing was performed, Sanger verification and pedigree co-segregation were performed for suspected pathogenic mutation sites. According to the law of inheritance, family history was analyzed to establish its genetic type. Mutational loci pathogenicity was analyzed according to the American College of Medical Genetics (ACMG) guidelines and 4 online tools.Results:Two CORD families showed autosomal recessive inheritance. The proband of pedigree 1 was female, 49 years old. Binocular vision loss with photophobia lasted for 9 years and night blindness for 4 years. The BCVA of right eye and left eye were 0.03 and 0.06, respectively. The results of ERG showed that the amplitudes of dark adaptation 0.01 b-wave and dark adaptation 3.0 a-wave and b-wave in both eyes were slightly decreased, and the amplitudes of light adaptation 3.0 a-wave and b-wave were severely decreased. The proband of pedigree 2 was male, 30 years old. Vision loss in both eyes for 4 years. Denying a history of night blindness. The BCVA of right eye and left eye were 0.3 and 0.2, respectively. The results of ERG showed that the amplitudes of dark adaptation 0.01 b-wave and dark adaptation 3.0 a-wave and b-wave in both eyes were slightly decreased, and the amplitudes of light adaptation 3.0 a-wave and b-wave were severely decreased. The color of optic disc in both eyes was light red, the macular area was atrophic, the foveal reflection disappeared, and the peripheral retina was punctate pigmentation. The main fundus changes in 2 patients were macular atrophy. The proband of pedigree 1 carried compound heterozygous variations c.439-2A>G (M1) and c.676delT (p.F226fs) (M2) on CDHR1 gene. Her father and mother carried M2 and M1 heterozygous mutations, respectively. The proband of pedigree 2 carried compound heterozygous variations c.2665dupC (p.L889fs) (M3) and c.878T>C (p.L293P) (M4) on C2orf71 gene. His father and mother carried M4 and M3 heterozygous mutations, respectively. According to ACMG guidelines and on line tools, 4 variations were considered as pathogenic level. Conclusions:M1 and M2 of CDHR1 gene and M3 and M4 of C2orf71 gene are new pathogenic mutations of CORD. All patients presented with the clinical phenotype of decreased visual acuity and macular atrophy.

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.

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.

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.

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.

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.

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.