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ObjectiveTo investigate natural outcome of moderate- and high-risk human papillomavirus (HPV) infection and influencing factors of persistent infection among Kazak women in Xinjiang Uygur Autonomous Region (Xinjiang). MethodsA baseline survey was conducted among 2 000 Kazakh women (25 – 64 years old) recruited using cluster sampling at Tacheng region of Xinjiang during June – August 2018. Relevant information of the women were collected with questionnaire interview, routine gynaecological examination, laboratory test, and biopsy if required. A year later, follow-up detections of HPV infection, cell cycle protein-dependent kinase inhibitor (P16), liquid-based cytology (LBC) were performed among 10% of the women negative for HPV and all the women positive for HPV infection at the baseline survey. An end follow-up survey was conducted among all the participants of the study two years after the baseline survey. SPSS 21.0 statistical software was used to analyze influencing factors for natural regression and persistence of HPV infection. ResultsIn the baseline survey, totally 291 HPV-positive women were detected, with 208 monotypic infections (including 164, 14, and 30 high-, moderate-, and low-risk HPV infections) and 83 multiple infections (80, 16, and 33 high-, moderate-, and low-risk HPV infections). At one-year follow-up detection among 193 baseline moderate- high-risk HPV positive women, 92 (47.67%) were found having persistent infection (with top five strains of HPV33, HPV35, HPV58, HPV18 and HPV16 in baseline detection) and 101 (52.33%) were observed having HPV clearance for strains of HPV45, HPV73, HPV82, and HPV83 in the baseline detection; while at the end follow-up among 186 baseline moderate- high-risk HPV positive women, 77 (41.40%) had persistent infection (with top five strains of HPV35, HPV16, HPV33, HPV18 and HPV59 in baseline detection) and 109 (58.60%) showed HPV clearance. The results of logistic regression analysis revealed that the age of ≤ 20 years at first sex (odds ratio [OR] = 1.85, 95% confidence interval [95%CI]: 1.12 – 3.03), having syphilis infection (OR = 3.09, 95%CI: 1.15 – 8.32), and being menopause (OR = 3.09, 95%CI: 1.91 – 5.00) were risk factors for persistent moderate- and high-risk HPV infection during the two-year follow-up period. ConclusionPersistent moderate- and high-risk HPV infection are more likely to occur for infections of HPV35/HPV16/HPV33/HPV18/HPV59 and main risk factors for the persistent infection include early age at first sex, syphilis infection and menopause among Kazakh women in Xinjiang.

China has the considerable disease burden of cervical cancer, with the mortality and morbidity of cervical cancer showing an increasing and younger trend. Facing to the critical situation of cervical cancer control, it is urgent to explore the new methods that suitable for different resource areas for the early detection and treatment of cervical cancer. Recently, great progress has been made in the field of AI image classification, and scientists have developed many algorithms to identify cervical lesions and conducted corresponding studies on their accuracy. Here, by reviewing the papers published at home and aboard, which studied the applications value of AI in cervical cytology screening, colposcopy examination, diagnosis and treatment of cervical cancer, we summarized and discussed the current progress and challenges for AI's application in the area of cervical cancer control, in order to provide solid evidence for the future use of AI in improving human health.

While HC2 and GP5+/6+ PCR‐EIA were pivotal in test validation of new HPV assays, they represent the first generation of comparator tests based upon technologies that are not in widespread use anymore. In the current guideline, criteria for second‐generation comparator tests are presented that include more detailed resolution of HPV genotypes. Second‐generation comparator tests should preferentially target only the 12 genotypes classified as carcinogenic (IARC‐group I), and show consistent non‐inferior sensitivity for CIN2+ and CIN3+ and specificity for ≤CIN1 compared to one of the first‐generations comparators, in at least three validation studies using benchmarks of 0.95 for relative sensitivity and 0.98 for relative specificity. Validation should take into account used storage media and other sample handling procedures. Meta‐analyses were conducted to identify the assays that fulfill these stringent criteria. Four tests fulfilled the new criteria: (1) RealTime High‐Risk HPV Test (Abbott), (2) Cobas‐4800 HPV test (Roche Molecular System), (3) Onclarity HPV Assay (BD Diagnostics), and (4) Anyplex II HPV HR Detection (Seegene), each evaluated in three to six studies. Whereas the four assays target 14 carcinogenic genotypes, the first two identify separately HPV16 and 18, the third assay identifies five types separately and the fourth identifies all the types separately. [ABSTRACT FROM AUTHOR]

More evidence from population-based cohort studies is required to confirm the application of methylation-based biomarkers in real-world settings. The cross-sectional and 24-month cumulative triage performance of a novel methylation assay targeting the host gene EPB41LE and HPV16/18 DNA L1/L2 regions among hrHPV-positive women was evaluated based on a population-based cohort study from China. Overall methylation positivity was 12.4% among hrHPV-positive women. Methylation-positive women had significantly higher risks of hrHPV persistence at 12M and 24M follow-up (RR12M = 1.9, 95%CI: 1.5–2.6 and RR24M = 1.7, 95%CI: 1.2–2.5). For CIN2+, cross-sectional triage sensitivity of methylation was similar to HPV16/18 (70.6% vs. 64.7%, pexact = 1.000), but was lower than cytology (94.1%), although not significantly (pexact = 0.213). The specificity (91.2%) of methylation was significantly higher than other triage methods (p < 0.001 for all). The longitudinal sensitivity of methylation over 24M follow-up was 56.0%, lower (but not significantly so) than HPV16/18 (64.0%, pexact = 0.688) and cytology (76.0%, pexact = 0.125). Methylation testing showed high positive predictive values for CIN2+ (41.4% at baseline, 50.0% at 24-month), while the CIN2+ risk of methylation negative women (cNPV) remained considerable (2.5% at baseline, 6.9% at 24-month). Study findings indicate that methylation has better specificity and predictive values for the presence or development of cervical precancer and might therefore be considered for the strategy of HPV screening and methylation triage followed by immediate treatment of triage-positive women and delayed follow-up of hrHPV-positive/methylation-negative women. [ABSTRACT FROM AUTHOR]

Introduction: This cross-sectional study evaluated the involvement of patients with advanced colorectal cancer (CRC) in treatment decision-making, assessed the treatment efficacy according to their self-reports, and investigated the influencing factors. Methods: Patients with advanced CRC were recruited from 19 hospitals from March 2020 to March 2021 by a multi-stage multi-level sampling method. A selfdesigned questionnaire was used to collect demographic and clinical characteristics, involvement of CRC patients in treatment decision-making, treatment methods, and self-reported efficacy. Univariate and unordered multinomial logistic regression analyses were used to evaluate the factors affecting the involvement in treatment decision-making and self-reported efficacy. Results: We enrolled 4533 patients with advanced CRC. The average age at diagnosis was 58.7 ± 11.8 years. For the treatment method, 32.4% of patients received surgery combined with chemotherapy, 13.1% of patients underwent surgery combined with chemotherapy and targeted therapy, and 9.7% of patients were treated with surgery alone. For treatment decision-making, 7.0% of patients were solely responsible for decision-making, 47.0% of patients shared treatment decision-making with family members, 19.0% of patients had family members solely responsible for treatment decision-making, and 27.0% of patients had their physicians solely responsible for treatment decision-making. Gender, age, education level, family income, marital status, treatment cost, hospital type, and treatment method were significantly associated with the involvement of patients in treatment decision-making. A total of 3824 patients submitted selfreported efficacy evaluations during treatment. The percentage of patients with good self-reported efficacy was 76.5% (for patients treated for the first time), 61.7% (for patients treated for the second time), and 43.2% (for patients treated after recurrence and metastasis), respectively. Occupation, education level, average annual family income, place of residence, time since cancer diagnosis, hospital type, clinical stage, targeted therapy, and involvement in treatment decision-making were the main influencing factors of self-reported efficacy of treatment. Discussion: Conclusively, CRC patients are not highly dominant in treatment decision-making and more likely to make treatment decisions with their family and doctors. Timely and effective communication between doctors and patients can bolster patient involvement in treatment decision-making. [ABSTRACT FROM AUTHOR]

Background: Cervical cancer screening with cytology suffers from low sensitivity, whereas the efficiency of human papillomavirus (HPV)‐based screening is limited by low specificity. The authors evaluated a novel p16INK4a immunocytology approach in cervical cancer screening compared with HPV‐based and cytology‐based screening. Methods: In total, 2112 women aged 49 to 69 years from Shanxi, China were screened from March to July 2019. HPV testing, liquid‐based cytology (LBC), and p16INK4a immunocytology were performed on samples from all women. Any positive result triggered a referral to colposcopy with biopsy, if indicated. Screening performance for detecting cervical intraepithelial neoplasia grade 2 and 3 or worse (CIN2+/CIN3+) was evaluated using multiple algorithms. Results: p16INK4a had a lower positive rate (10.0%) than LBC abnormality (vs 12.1%; P =.004) and a high‐risk HPV positivity (21.4%; P <.001). For the detection of CIN3+, the relative sensitivity of p16INK4a compared with HPV and LBC was 0.93 (95% CI, 0.82‐1.07) and 1.12 (95% CI, 0.95‐1.32), respectively. The specificity of p16INK4a was significantly higher than that for HPV and LBC, with a relative specificity of 1.13 (95% CI, 1.11‐1.16) and 1.02 (95% CI, 1.01‐1.04), respectively. In addition, p16INK4a alone yielded a clinical performance very similar to that of the current mainstream strategy of using HPV16/18 with reflex cytology (ASC‐US+, atypical squamous cells of undetermined significance or worse). The immediate risk of CIN3+ was 14.6% if p16INK4a results were positive and 0.2% if p16INK4a results were negative. Conclusions: With minimal colposcopy referrals, p16INK4a screening demonstrated promising utility for risk stratification and yielded a better balance between sensitivity and specificity compared with HPV and LBC primary screening. Moreover, with accuracy and efficiency similar to what is achieved using mainstream cotest algorithms, p16 may simplify the screening practice. More evidence will be required before clinical recommendation. This evaluation of a novel p16INK4a test demonstrates that p16INK4a may be a promising alternative to cytology for primary screening. Moreover, with screening efficacy similar to that of mainstream human papillomavirus‐cytology cotest algorithms, p16INK4a screening has great potential to simplify screening practice. [ABSTRACT FROM AUTHOR]

The management of HPV‐positive women becomes particularly crucial in cervical cancer screening. Here we assessed whether detection of E6 or E7 oncoproteins targeting eight most prevalent HPV types could serve as a promising triage option. Women (N = 1,416) aged 50–60 from Shanxi, China underwent screening with HPV testing and liquid‐based cytology (LBC), with any positive results referring to colposcopy and biopsy if necessary. Women with HPV‐positive results received further tests using DNA‐based genotyping, E6 or E7 oncoprotein detection targeting HPV16/18 (for short: E6 (16/18) Test) or HPV16/18/31/33/35/45/52/58 (for short: E6/E7 (8 types) Test), respectively. Among HPV‐positive women, E6/E7 (8 types) oncoproteins had lower positivity (17.37%) compared to DNA‐based genotyping for same eight types (58.30%) and LBC with ASC‐US threshold (50.97%); HPV16 was the genotype showing the highest frequency (8.49%) for oncoprotein detection followed by HPV52 (3.47%), 58 (2.32%), 33 (1.54%), 18 (1.16%), 45 (0.77%), 35 (0.39%) and 31 (0%). For detection of cervical intraepithelial neoplasia Grade 3 or higher (CIN3+), E6/E7 (8 types) Test had similar sensitivity (100.00%) and superior specificity (85.94%) as well as positive predictive value (PPV, 22.22%) compared to both LBC and DNA‐based genotyping (8 types); For detection of CIN2+, E6/E7 (8 types) Test was less sensitive (67.74%) but still more specific (89.47%) and risk predictive with PPV of 46.67%. Notably, E6/E7 (8 types) Test remarkably decreased the number of colposcopies needed to detect one CIN2+ and CIN3+ (2.14 and 4.50). E6/E7 oncoprotein detection showed a good "trade‐off" between sensitivity and specificity with more efficient colposcopy referrals, which is of great importance to maximize the benefits of HPV‐based screening program, especially applicable for the areas with high HPV prevalence and low‐resources. What's new? DNA‐based testing for human papillomavirus (HPV) is a sensitive method to detect HPV infection, but leads to considerable over referral and even overtreatment of HPV‐associated lesions. Here the authors expanded on a previously established DNA test specific for the E6 oncoprotein and showed better performance including higher predictive value of E6/E7 oncoprotein detection with inclusion of eight prevalent HPV types. Improved triage of HPV‐infected women is important especially in resource‐limited areas, helping to make HPV‐based screening programs economically feasible. [ABSTRACT FROM AUTHOR]

Background: The detection of human papillomavirus (HPV) E6/E7 mRNA indicates a risk of further deterioration in cervical lesions. We explored the clinical value of HPV E6/E7 mRNA detection in cervical cancer screening in women positive for HPV or with abnormal thin-prep cytology test (TCT) results in the Xinjiang region of China. Methods: A total of 6,800 women were screened in our hospital for cervical cancer by both TCT and HPV DNA testing from August 2013 to June 2015. Of these, 197 had abnormal cytological or HPV test results and subsequently underwent HPV E6/E7 mRNA detection and histopathological examination, while 101 underwent an HPV DNA typing test. Using pathological results as the gold standard, we compared the accuracies of HPV E6/E7 mRNA detection or HPV DNA type testing alone, in parallel, and in series for diagnosing high-grade cervical lesions. Results: Pathological examination revealed 80 cases of chronic cervicitis, 16 cases of cervical intraepithelial neoplasia (CIN)-I, 50 cases of CIN-II-III, and 51 cases of cervical cancer. The area under the receiver operating characteristic (ROC) curve (AUC) for diagnosing high-grade cervical lesions by HPV E6/E7 mRNA detection was 74.95% (sensitivity, 85.15%; specificity, 66.67%; Youden index, 0.139; positive predictive value, 72.9%; negative predictive value, 81.0%; positive likelihood ratio, 2.555; negative likelihood ratio, 0.222; and post-test probability, 72.9%). Conclusions: HPV E6/E7 mRNA detection is superior to HPV DNA type testing for diagnosing high-grade cervical lesions. [ABSTRACT FROM AUTHOR]

Background The associations between sexual dysfunction (SD) and sleep disorders, sleep quality, and sleep duration remain unclear. Aim To assess the relationship between sleep and SD through a literature review and meta-analysis. Methods The PubMed, Scopus, Embase, Ovid MEDLINE, and Cochrane Library databases were systematically searched from inception to November 10, 2022. Outcomes Pooled relative risks and 95% CIs were used to examine the association of sleep disorders with SD in longitudinal studies. Pooled odds ratios (ORs) and 95% CIs were used to examine the associations between SD and sleep disorders, sleep quality, and sleep duration in cross-sectional studies. Results Forty-three articles, including 11 longitudinal studies and 32 cross-sectional studies, were included in the quantitative analysis. The pooled relative risk of SD in patients with sleep disorders was 1.97 in longitudinal studies (95% CI, 1.46-2.67, P <.001; heterogeneity: I 2 = 95.0%, P <.001), while the pooled OR of SD in patients with sleep disorders was 2.05 in cross-sectional studies (95% CI, 1.76-2.39, P <.001; heterogeneity: I 2 = 91.4%, P <.001). When compared with controls, subjects with poor sleep quality had a 1.49-fold increased risk of SD (OR, 1.49; 95% CI, 1.31-1.71, P <.001; heterogeneity: I 2 = 73.4%, P <.001). In addition, short sleep duration was associated with the risk of SD (OR, 1.14; 95% CI, 1.06-1.22, P <.001; heterogeneity: I 2 = 0.0%, P  = .849). Clinical Implications The risk of SD is significantly increased in patients with sleep disorders and poor sleep quality, indicating that clinicians should monitor sleep among patients with SD. Strengths and Limitations This study is the most comprehensive meta-analysis of the association between sleep and SD to date. However, different sleep disorders may have varying associations with sleep duration and sleep quality; thus, we could not identify the independent effects across the studies. Conclusion Our systematic review and meta-analysis results suggest that sleep disorders, especially obstructive sleep apnea, increase the risk of SD in men and women. Poor sleep quality is significantly associated with SD. Short sleep duration is associated with an increased risk of SD. [ABSTRACT FROM AUTHOR]

More evidence from population-based cohort studies is required to confirm the application of methylation-based biomarkers in real-world settings. The cross-sectional and 24-month cumulative triage performance of a novel methylation assay targeting the host gene EPB41LE and HPV16/18 DNA L1/L2 regions among hrHPV-positive women was evaluated based on a population-based cohort study from China. Overall methylation positivity was 12.4% among hrHPV-positive women. Methylation-positive women had significantly higher risks of hrHPV persistence at 12M and 24M follow-up (RR 12M = 1.9, 95%CI: 1.5-2.6 and RR 24M = 1.7, 95%CI: 1.2-2.5). For CIN2+, cross-sectional triage sensitivity of methylation was similar to HPV16/18 (70.6% vs. 64.7%, p exact = 1.000), but was lower than cytology (94.1%), although not significantly (p exact = 0.213). The specificity (91.2%) of methylation was significantly higher than other triage methods ( p < 0.001 for all). The longitudinal sensitivity of methylation over 24M follow-up was 56.0%, lower (but not significantly so) than HPV16/18 (64.0%, p exact = 0.688) and cytology (76.0%, p exact = 0.125). Methylation testing showed high positive predictive values for CIN2+ (41.4% at baseline, 50.0% at 24-month), while the CIN2+ risk of methylation negative women (cNPV) remained considerable (2.5% at baseline, 6.9% at 24-month). Study findings indicate that methylation has better specificity and predictive values for the presence or development of cervical precancer and might therefore be considered for the strategy of HPV screening and methylation triage followed by immediate treatment of triage-positive women and delayed follow-up of hrHPV-positive/methylation-negative women.

Objective: To investigate the prevalence and genotype distribution of high-risk human papillomavirus (HR-HPV) and the correlation between cervical lesions and analyze the risk factors for HR-HPV infection. Methods: In June 2018, a population-based study for cervical cancer screening in Tuoli county of Xinjiang Uygur Autonomous Region was conducted. A total of 2 000 Kazak women aged 25-64 years were included in the study. Three cervical exfoliated cells samples were collected from them for careHPV, PCR HPV, p16(INK4a), and liquid-based cytology (LBC) tests. Women with any positive test were referred for colposcopy with biopsies taken at abnormal sites. Histo-pathological diagnoses were used as the gold standard. Results: The overall prevalence of HPV was 14.55%, among which the infection rate of HR-HPV was 12.90%, which was even higher in the 50-54 years age group. The most prevalent genotypes of HR-HPV were HPV16 (2.80%), HPV51(2.35%), HPV52 (1.70%), HPV56 (1.50%), and HPV39 (1.20%). The most common HPV infection was a single infection (71.48%). In the age group of 50-54 years, the multiple infection rates were higher, with the majority of double infection (69.88%), and HPV42 and 56 were the most common co-infection types. HPV16 (31.82%), HPV51 (27.27%) and HPV18 (13.64%) were higher in cervical intraepithelial neplasia grade 1, HPV16 (57.14%) was higher in cervical intraepithelial neplasia grade 2, and HPV16 (55.56%) and HPV18 (33.33%) were higher in cervical intraepithelial neplasia grade 3 or worse. Results from the multivariate logistic regression analysis showed that higher education, menopause, and syphilis infection increased the HPV infection. Conclusions: The most common prevalence genotypes of HR-HPV among Kazak women were HPV16, HPV51, and HPV52. The infection rate of HR-HPV among Kazak women was correlated with education level, menopausal status, and syphilis infection. Measures should be taken targeting high-risk factors. This result suggests that STD patients and women aged 50 and above should be encouraged for screening.

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.

Objective: To assess the risk of cervical cancer and high grade cervical intraepithelial in women with negative human papillomavirus (HPV) and cytology atypical squamous cells of undetermined significance (ASC-US) and to provide evidence for clinical management., Methods: We pooled 17 population-based cross-sectional studies which were conducted across China from 1999 to 2008. Totally, 30 371 women aged 17-59 were included in these studies. All women received liquid-based cytology test (LBC), HPV testing (hybrid capture 2 test, HC2) and visual inspection with acetic acid test (VIA). Women with any positive result from above tests were referred to colposcopic examination. Totally, 28 810 women with complete results from HPV, cytology and pathology were included in the final analysis. Women with negative HPV (LBC-/HPV-) or negative cytology (LBC-) results served as the control, respectively. Risk on high grade cervical intraepithelial neoplasia (CIN2+) was calculated for women with HPV negative and ASC-US results (ASC-US/HPV-)., Results: There were 22 003 women with LBC-/HPV-, 24 139 women with LBC-, and 1 834 with ASC-US/HPV- indentified in our study. CIN2+prevalence rates to the above women appeared as 0.05%, 0.36% and 0.16%, respectively. Compared with women with LBC-/HPV- and women with LBC-, the odds ratios (ORs) for CIN2+in women with ASC-US/HPV-were 3.00 (95%CI: 0.85-10.65) and 0.46 (95%CI:0.15-1.45), with adjusted ORs as 4.00 (95%CI: 1.08-14.87) and 0.47(95%CI: 0.15-1.49), respectively., Conclusions: The risk of CIN2+ in women with ASC-US/HPV- was in between the risks of women with LBC-/HPV- or with LBC-. Based on the "equal risk, equal management" principle, women with ASC-US/HPV- were suggested to be followed under the '3-year interval' program, which was the same as for those cytology negative women. However, in areas with limited health resources, the follow-up interval can be extended to 5 years, similar to the management on women with LBC-/HPV-.