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Trial Registration: The LTFU study was registered at the Chinese Clinical Trial Registry, ChiCTR2100052313.

Data investigating the natural history of high-risk human papillomavirus (HR-HPV) infection in mid-adult women compared with young adult women from regions exhibiting a bimodal distribution pattern are scarce. From November 2012 to September 2019, 3681 healthy women aged 18-45 years from the control group of a bivalent HPV vaccine Phase 3 trial in China were followed over 5.5 years. At scheduled visits (Day 0, months 7, 12, 18, 24, 30, 42, 54, and 66), cervical samples were collected for ThinPrep Pap tests and HPV DNA testing, women with abnormal cytology were referred for colposcopy. Data was analyzed using Cox regression model and a competing risk model. Sensitivity analyses were performed among participants attending all scheduled visits. The incidences of HR-HPV persistent infections (over 6 months [6mPIs]) were 35.5 and 29.0 per 1000 person-years (PYs) (hazard ratio [HR] = 1.21, 95% confidence interval [CI]: 1.00, 1.46), and HR-HPV associated CIN grade 2 or greater (CIN2+) were 4.3 and 1.9 per 1000 PYs (HR = 2.31, 95% CI: 1.25, 4.26) in women aged 18-26 and 27-45 years. Competing risk models showed that the cumulative incidence of HR-HPV infections that progressed to CIN2+ was significantly higher in women aged 18-26 than in women aged 27-45 (5.3% vs. 2.9%, Gray's test p = .0291). The cumulative clearance rates of HR-HPV infections in women aged 18-26 and 27-45 were similar (94.7% vs. 95.8%, Gray's test p = .3309) during the study period. In conclusion, although mid-adult women exhibit lower incidences of HR-HPV infection and associated cervical lesions compared to young women, this population continues to face a substantial risk of acquiring causal HPV infections, which may progress to cervical lesion., (© 2024 UICC.)

Background: Cervical cancer is a major health threat in the female population. Human immunodeficiency virus (HIV)-positive women encounter a higher risk of cervical cancer. It is significant to promote cervical cancer screening attendance among HIV-positive women. Little is known about the awareness, attendance, and attitudes toward cervical cancer screening, as well as the associated factors, among Chinese HIV-positive women., Methods: A cross-sectional study was conducted among 411 HIV-positive women attending a large ART clinic in Yunnan, an HIV-endemic province in China. Participants were recruited using the convenient sampling method from January 2019 to August 2020. An interviewer-administered semi-structured questionnaire was utilized to collect information on socio-demographic and behavioral characteristics, clinical characteristics related to HIV infection, awareness, attendance, and attitudes toward cervical cancer screening. Binary logistic regression analyses were used to determine factors associated with awareness, attendance, and attitude toward cervical cancer screening., Results: Some 69.8% (287) of the participants were aware of cervical cancer screening, but only 27.7% (114) had attended screening within 3 years. After receiving a brief health education, 72.3% (297) of the participants exhibited a positive attitude toward cervical cancer screening. Participants with a higher education background and longer duration of antiretroviral therapy were more likely to be aware of cervical cancer screening and have up-to-date screening. The up-to-date screening attendance was also influenced by age, smoking status, and health insurance. Single participants were less likely to show a positive attitude toward cervical cancer screening compared married or cohabiting counterparts. The main facilitators to attending cervical cancer screening were health promotion activity and well-organized programs, while the main barriers were high costs of the service and inadequate awareness., Conclusions: Although most HIV-positive women attending a large ART clinic in Yunnan were aware of cervical cancer screening, the up-to-date attendance was low. It is crucial to conduct health education and promotion through efficient channels to improve awareness and attendance. The discrepancy between awareness and attendance also emphasized the importance of adopting appropriate screening strategies and powerful health policies that can foster the attendance of cervical cancer screening among HIV-positive women. Efforts should be devoted to constructing a comprehensive healthcare system with high accessibility in China for cervical cancer prevention and management for HIV-positive women., Competing Interests: Declarations. Competing interests: The authors declare no competing interests. Ethics approval and consent to participate: Ethical approval was obtained from the Ethics Committee of the National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China (Approval Number: 17–205/1461). All participants in this study were voluntary and provided written informed consent. All methods were performed following relevant guidelines and regulations. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Background: CareHPV is a highly promising screening HPV assay that functions as a simplified and rapid point-of-care test, making it particularly well-suited for low-resource areas. It exhibits high sensitivity for detecting cervical precancerous lesions in cross-sectional study design. However, there is still limited evidence on the long-term protection of careHPV testing in the practical setting., Methods: A government-led cervical cancer screening program was implemented in Ordos City, China, specifically targeting female residents aged 35-64 years since 2016. CareHPV specimens were collected and visual inspection with acetic acid and Lugol iodine (VIA/VILI) was performed in the baseline screening. Women who were HPV-positive or VIA/VILI-suspected cancer at baseline were invited for a one-year follow-up screening. At the same time, those who were HPV-negative were scheduled for a 5-year rescreening. Women diagnosed with cervical intra-epithelial neoplasia grade 2 or worse (CIN2+) would be referred to clinical treatment as per the clinical guidelines. The current study includes participants who had valid baseline screening results and attended follow-ups with valid careHPV results conducted between January 2017 and December 2021, aiming to assess the long-term risk stratification for careHPV. Cumulative incidence rate (CIRs) and hazard ratio (HRs) for CIN2+ were calculated, using survival analysis., Results: Among the 179,306 women enrolled in the baseline screening between 2016 and 2020, 12.60 % tested positive for careHPV, with 657 cases of CIN2+ identified. The final analysis included 18,562 women in our study, of whom 58.54 % were careHPV-positive at baseline. The final analysis consisted of 17,905 women who underwent screening between 2016 and 2020 and attended follow-ups from 2017 to 2021, with valid HPV results, and 657 women who identified as CIN2+ at the baseline. The 5-year CIRs were 0.003 and 0.101 among women who tested negative and positive for baseline careHPV, respectively. The 5-year CIRs for developing CIN2+ during follow-ups were 0.009, 0.009, and 0.11 for the groups of women who transitioned from careHPV-negative to positive (831, 4.64 %), careHPV-positive to negative (6688, 37.35 %), and maintained a stable positive careHPV status (3535, 19.74 %), respectively., Conclusions: Our findings support the long-term safety and protection of careHPV testing in 5-year follow-ups of screening programs. CareHPV represents a viable option for regions with limited healthcare resources., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: This study was supported by the Bill and Melinda Gates Foundation (INV-031449), the CAMS Innovation Fund for Medical Sciences (CIFMS 2021-I2M-1-004), and the National High Level Hospital Clinical Research Funding (2022-PUMCH-D-003)., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: The high price of HPV vaccines remains a significant barrier to vaccine accessibility in China, hindering the country's efforts toward cervical cancer elimination and exacerbating health inequity. We aimed to inform HPV vaccine price negotiations by identifying threshold prices that ensure that a government-funded HPV vaccination programme is cost-effective or cost-saving., Methods: We used a previously validated transmission model to estimate the health and economic impact of HPV vaccination over a 100-year time horizon from a healthcare payer perspective. Threshold analysis was conducted considering different settings (national, rural, and urban), cervical cancer screening scenarios (cytology-based or HPV DNA-based, with different paces of scale-up), vaccine types (four types available in China), vaccine schedules (two-dose or one-dose), mode of vaccination (routine vaccination with or without later switching to high-valency vaccines), willingness-to-pay thresholds, and decision-making criteria (cost-effective or cost-saving). Furthermore, we examined the budget impact of introducing nationwide vaccination at the identified threshold prices., Findings: Using the current market price, national routine HPV vaccination with any currently available vaccine is unlikely cost-effective. Under a two-dose schedule, the prices of the four available HPV vaccine types cannot exceed $26-$36 per dose (44.1%-80.2% reduction from current market prices) depending on vaccine type to ensure the cost-effectiveness of the national programme. Adopting vaccination at threshold prices would require an annual increase of 72.18%-96.95% of the total annual National Immunization Programme (NIP) budget in China. A cost-saving routine vaccination programme requires vaccine prices of $5-$10 per dose (depending on vaccine type), producing a 21.38%-34.23% increase in the annual NIP budget. Adding the second dose is unlikely to be cost-effective compared to a one-dose schedule, with the threshold price approaching or even falling below zero. Rural pilot vaccination programmes require lower threshold prices compared with a national programme., Interpretation: Our study could inform vaccine price negotiation and thus facilitate nationwide scale-up of current HPV vaccination pilot programmes in China. The evidence may potentially be valuable to other countries facing HPV introduction barriers due to high costs. This approach may also be adapted for other contexts that involve the introduction of a pricy vaccine., Funding: CAMS Innovation Fund for Medical Sciences (CIFMS); Bill & Melinda Gates Foundation., Competing Interests: FZ reports receiving grants from GlaxoSmithKline Biologicals, Merck & Co., and Xiamen Innovax Biotech to her institution for conducting clinical trials on the HPV vaccines. YQ reports receiving grants from Merck & Co., and Xiamen Innovax Biotech to his institution for similar clinical trials. YL reports receiving grants from BMGF, WHO, and InnoHK to her institution. MJ reports receiving research grants from NIHR, RCUK, BMGF, WHO, Gavi, Wellcome Trust, European Commission, InnoHK, TFGH, and CDC to his institution. The other co-authors declare no competing interests., (© 2024 The Author(s).)

Cervical cancer is a severe threat to women's health. The majority of cervical cancer cases occur in developing countries. The WHO has proposed screening 70% of women with high-performance tests between 35 and 45 years of age by 2030 to accelerate the elimination of cervical cancer. Due to an inadequate health infrastructure and organized screening strategy, most low- and middle-income countries are still far from achieving this goal. As part of the efforts to increase performance of cervical cancer screening, it is necessary to investigate the most accurate, efficient, and effective methods and strategies. Artificial intelligence (AI) is rapidly expanding its application in cancer screening and diagnosis and deep learning algorithms have offered human-like interpretation capabilities on various medical images. AI will soon have a more significant role in improving the implementation of cervical cancer screening, management, and follow-up. This review aims to report the state of AI with respect to cervical cancer screening. We discuss the primary AI applications and development of AI technology for image recognition applied to detection of abnormal cytology and cervical neoplastic diseases, as well as the challenges that we anticipate in the future., Competing Interests: No potential conflicts of interest are disclosed., (Copyright © 2024 The Authors.)

Background: The region-specific importance of carcinogenic HPV genotypes is required for optimizing HPV-based screening and promoting appropriate multivalent HPV prophylactic vaccines. This information is lacking for Ningbo, one of the first cities of China's Healthy City Innovation Pilot Program for Cervical Cancer Elimination. Here, we investigated high-risk HPV (HR-HPV) genotype-specific distribution and attribution to biopsy-confirmed cervical intraepithelial neoplasia grade 2 or worse (CIN2+) before mass vaccination in Ningbo, China., Methods: A total of 1393 eligible CIN2+ archived blocks (including 161 CIN2, 1107 CIN3, and 125 invasive cervical cancers [ICC]) were collected from 2017 to 2020 in Ningbo. HR-HPV DNA was genotyped using the SPF 10 -DEIA-LiPA 25 version 1 detection system and the SureX HPV 25X Genotyping Kit. Genotype-specific attribution to CIN2+ was estimated using a fractional contribution approach., Results: Ranking by the attributable proportions, HPV16 remained the most important genotype in both cervical precancers and cancers, accounting for 36.8% of CIN2, 53.2% of CIN3, and 73.3% of ICC cases. Among cervical precancers, HPV52 (17.3% in CIN2, 12.7% in CIN3) and HPV58 (13.9%, 14.9%) ranked second and third, while HPV33 (8.3%, 7.9%) and HPV31 (6.5%, 4.1%) ranked fourth and fifth, respectively. However, among ICCs, HPV18 (5.7%) accounted for the second highest proportion, followed by HPV33 (5.4%), HPV58 (4.0%), and HPV45 (3.2%). HPV18/45 together accounted for 46.8% of adenocarcinomas, which was slightly lower than that of HPV16 (47.7%). The remaining HR-HPV genotypes (HPV35/39/51/56/59/66/68) combined accounted for only 6.7% of CIN2, 2.9% of CIN3, and 4.2% of ICC., Conclusions: With Ningbo's strong medical resources, it will be important to continue HPV16/18 control efforts, and could broaden to HPV31/33/45/52/58 for maximum health benefits. However, different strategies should be proposed for other HR-HPV genotypes based on their lower carcinogenic risks., (© 2024. The Author(s).)

Objectives: The aim of the study was to evaluate the clinical performance of HBRT-H14, a real-time PCR-based assay that separates human papillomavirus (HPV) 16 and HPV18 from 12 other high-risk (HR) HPV types, in population according to Chinese guideline., Methods: A total of 9829 eligible women aged 21-64 years from Henan, Shanxi, and Guangdong provinces were performed by HBRT-H14 testing and liquid-based cytology (LBC) screening at baseline and followed up for 3-year. The sensitivity, specificity, positive predictive value (absolute risk), and negative predictive value of LBC diagnosis and HPV testing were calculated for cervical intraepithelial neoplasia grade 2 or worse (CIN2+) Lesions., Results: At baseline, 80 (0.81%) participants were diagnosed with CIN2+. HR-HPV with reflex LBC had a significantly higher sensitivity (78/80, 97.50% [95% CI, 91.34-99.31%] vs. 62/80, 77.50% [67.21-85.27%], McNemar's test p < 0.001), and a slightly lower specificity (8528/9749, 87.48% [86.80-88.12%] vs. 8900/9749, 91.29% [90.72-91.83%], McNemar's test p < 0.001) than LBC with reflex HR-HPV for CIN2+. 7832 (79.6%) participants completed 3-year follow-up and 172 (2.20%) participants were cumulatively diagnosed with CIN2+. Compared with LBC with reflex HR-HPV, HR-HPV with reflex LBC significantly increased the sensitivity (161/172, 93.60% [88.91-96.39%] vs. 87/172, 50.58% [43.18-57.96%], McNemar's test p < 0.001), but marginally decreased the specificity (6776/7660, 88.46% [87.72-89.16%] vs. 6933/7660, 90.51% [89.83-91.15], McNemar's test p < 0.001). In addition, the absolute 3-year risk of CIN2+ in HPV16/18-positive individuals was as high as 33% (80/238), whereas the risk in the HPV-negative population was only 0.16% (11/6787), much lower than those in the negative for intraepithelial lesion or malignancy population (1.21%, 85/7018). Moreover, similar results were found in women ≥30 years old., Discussion: The study has indicated that HBRT-14 has a reliable clinical performance for use in cervical screening. The validated HPV test would improve the quality of population screening., (Copyright © 2024. Published by Elsevier Ltd.)

Competing Interests: Competing interests: We have read and understood BMJ policy on declaration of interests and have the following interests to declare: YLQ and FHZ have received grants through their institution from GlaxoSmithKline Biologicals, Merck and Co, and Xiamen Innovax Biotech Co to undertake clinical trials on the HPV vaccine. Provenance and peer review: Commissioned; externally peer reviewed.

Aims: The optimal sampling methods for detecting human papillomavirus (HPV) in male genital sites remain unclear. This study aimed to assess the performance, acceptability, and comfort of two sampling techniques for male genital HPV detection., Methods and Results: A total of 490 men aged 18-45 were randomly assigned in a 1:1 ratio to undergo either the rub-brush (nail file followed by swab) or brush-only method (swab only) for sampling at external genitalia sites (PGS) and perineum/perianal (PA) sites. HPV distribution, specimen validity (β-globin as a quality reference), and participant acceptability and comfort were evaluated between the two sampling methods. The brush-only method demonstrated non-inferiority in detecting 14 high-risk HPV types (16/18/31/33/35/39/45/51/52/56/58/59/66/68) compared to the rub-brush method in both PGS (18.9% vs. 16.9%) and PA (10.5% vs. 11.9%). Although no significant differences were observed in positive rates for other HPV types, the brush-only method had a significantly higher invalid rate in PA (8.5% vs. 1.5%). Approximately 85.0% of participants reported good acceptability and comfort with both sampling methods, regardless of anatomical sites., Conclusions: This study suggests comparable performance, acceptability and comfort between the two sampling techniques for HPV detection. However, the rub-brush method may offer an advantage in higher sample validity., (© The Author(s) 2024. Published by Oxford University Press on behalf of Applied Microbiology International.)

Background: We analyzed the prevalence and genotype distribution of multiple- or single-type cervical human papillomavirus (HPV) infections in a population of women in mainland China., Methods: PubMed, MEDLINE, and Chinese databases (CNKI, VIP, and Wan Fang) were searched for studies on HPV prevalence and the examination of this relationship. All analyses were performed using STATA (version 12.0). Data from selected studies were extracted into tables, and all included studies were weighted and summarized., Results: Thirty studies were included. The prevalence of single types (10.4%) and multiple types (4.7%) primarily occurred in healthy Chinese women, in which the dominant single-type infection was HPV16 (1.6%), 52 (1.5%), 58 (1.0%), and 18 (0.5%), and the dominant type of multiple infection was HPV16 (0.7%), 52 (0.7%), 58 (0.6%), and 18 (0.3%). The prevalence in North and South China was 14.3%, in which the prevalence of the single type was 10.41% and 8.27%, and the prevalence of multiple types was 4.00% and 6.52%, respectively., Conclusion: Mainland China exhibits unique type-specific single and multiple HPV infections. Overall single or multiple HPV prevalence varied across regions of China, whereas type-specific HPV differences were relatively small., (Copyright © 2024 Copyright: © 2024 Journal of Cancer Research and Therapeutics.)

Accumulating evidence has demonstrated that high-risk human papillomaviruses (HR-HPVs) are involved in the etiology of a subset of oropharyngeal squamous cell carcinoma (OPSCC). In this regard, the International Agency for Research on Cancer (IARC) has recommended direct molecular HPV testing. So far, there is no agreement on the most appropriate method for HPV detection on OPSCC formalin-fixed paraffin-embedded (FFPE) materials. In this study, we aimed to evaluate the performance of the high-sensitive SureX HPV assay in OPSCC FFPE tissues compared with LiPA-25 and p16 ink4a immunostaining. A retrospective series of FFPE primary OPSCC cases were diagnosed between 2008 and 2019 and provided by the Henan Cancer Hospital, China. The level of agreement of two assays was determined using Cohen's Kappa (κ) statistics. A total of 230 FFPE OPSCC samples from tumor resections (n = 160) and diagnostic biopsies (n = 70) were detected. Sixty-six (28.7%) and 70 (30.4%) samples were identified as HPV-DNA-positive by LiPA-25 and SureX, respectively, of which HPV16 was largely the most common type (95.5% vs 94.3%). We found a perfect concordance between LiPA-25 and SureX for HPV-DNA status (κ = 0.906, 95% CI: 0.875-0.937) and for HPV16 (κ = 0.925, 95% CI: 0.897-0.953). In addition, SureX and p16 ink4a immunostaining had a perfect concordance (κ = 0.917, 95% CI: 0.888-0.946). Moreover, the HPV-driven fraction, based on double positivity for HPV-DNA and p16 ink4a , was similar between SureX (63 of 230, 27.4%) and LiPA-25 (60 of 230, 26.1%). Similar results were found in samples from resections and biopsies. SureX and LiPA-25 are comparable. SureX could be used for routine HPV-DNA detection and genotyping on archival OPSCC FFPE tissues., (© 2024 Wiley Periodicals LLC.)

Objective: To assess the clinical values of extended human papillomavirus (HPV) genotyping in triage of high-risk HPV-positive women, focusing on the trade-off between cervical precancer detections and colposcopy referrals., Methods: A bivariate random-effects model was used to estimate the diagnostic accuracy of primary HPV screening with following triage strategies to detect cervical precancers: (i) partial genotyping for HPV16/18 combined with cytological testing at atypical squamous cells of undetermined significance threshold (used as the comparator), (ii) genotyping for HPV16/18/58/52, (iii) genotyping for HPV16/18/58/52/33, (iv) genotyping for HPV16/18/58/33/31, (v) genotyping for HPV16/18/58/52/33/31, and (vi) genotyping for HPV16/18/58/52/33/31/39/51. Internal risk benchmarks for clinical management were used to evaluate the risk stratification of each triage strategy., Results: A total of 16,982 women (mean age 46.1 years, range 17-69) were included in this analysis. For CIN3+ detection, triage with HPV16/18/58/33/31 genotyping achieved lower positivity (6.85% vs. 7.35%, p = 0.001), while maintaining similar sensitivity (91.35% vs. 96.42%, p = 0.32) and specificity (94.09% vs. 93.67%, p = 0.56) compared with the comparator strategy. Similar patterns were observed for CIN2+ detection. Women with a positive HPV16/18/58/33/31 genotyping test had high enough risk for CIN3+ for colposcopy referral, while the risk for women with a negative test was below the 1-year return decision threshold according to internal benchmarks., Conclusions: Our findings suggested extended HPV genotyping is of potential to be used as a triage technique integrated into HPV-based cervical cancer screening, leading to reduced need for colposcopy referral while maintaining similar disease detection and efficient risk stratification., (© 2024 The Author(s). Cancer Medicine published by John Wiley & Sons Ltd.)

Objective The current study aimed to inform the varied and limited research on clinical variables in the context of teletherapy. Questions remain about the comparative quality of therapeutic alliance and clinical outcome in the context of teletherapy compared to in-person treatment. Methods We utilized a cohort design and a noninferiority statistical approach to study a large, matched sample of clients who reported therapeutic alliance as well as psychological distress before every session as part of routine clinical practice at a university counseling center. A cohort of 479 clients undergoing teletherapy after the emergence of the COVID-19 pandemic was compared to a cohort of 479 clients receiving in-person treatment before the onset of the pandemic. Tests of noninferiority were conducted to investigate the absence of meaningful differences between the two modalities of service delivery. Client characteristics were also examined as moderators of the association between modality and alliance or outcome. Results Clients receiving teletherapy showed noninferior alliance and clinical outcome when compared to clients receiving in-person psychotherapy. A significant main effect on alliance was found with regard to race and ethnicity. A significant main effect on outcome was found with regard to international student status. Significant interactions on alliance were found between cohort and current financial stress. Conclusions Study findings support the continued use of teletherapy by demonstrating commensurate clinical process and outcome. Yet, it will be important for providers to be aware of existing mental health disparities that continue to accompany psychotherapy - in person and via teletherapy. Results and findings are discussed in terms of research and clinical implications. Future directions for researching teletherapy as a viable treatment delivery method are also discussed.

Background: Human papillomavirus (HPV) vaccination is a promising step toward cervical cancer elimination. This study was conducted to investigate the knowledge, attitude, and HPV vaccine uptake among female adults in mainland China based on a large e-commerce platform., Methods: We conducted a cross-sectional online survey of female adults between March 4 to April 20, 2022. The survey consisted of sociodemographic information, related knowledge, vaccination uptake, and attitudes toward vaccination. We included women aged 18-45 years in the final analysis. Logistic regressions were conducted to explore influencing factors associated with related knowledge, HPV vaccination uptake, and willingness to be vaccinated., Results: In total, 3,572 female adults (34 years, IQR 30-39) were included in the analysis. The majority of the participants were highly educated (78.7%) with a high monthly family income (79.0%). The median HPV knowledge score was 8.25 out of 11. More than 75% of respondents were unvaccinated, while 95.8% of unvaccinated female adults are willing to be vaccinated. Variables such as age, insurance, vaccination history, and whether one had heard of the HPV vaccine influence HPV vaccination practice (all p-values < 0.05). The main barriers to vaccination were vaccine inaccessibility and the high cost of the vaccine., Conclusion: The findings of our study highlight a moderate knowledge level, poor vaccination rate, and strong willingness to be vaccinated among Chinese female adults who were better educated and wealthier. Targeted health education and practical support should be provided in the future, to reduce gaps between vaccine uptake and vaccine acceptance., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Importance: Limited evidence supports the performance of human papillomavirus (HPV) DNA testing as a primary screening method, followed by triage with visual inspection with acetic acid, in areas with limited health care resources, as suggested by the 2021 World Health Organization guidelines., Objective: To evaluate the performance of visual inspection with acetic acid and Lugol iodine as a triage method for detecting cervical precancerous lesions among HPV-positive women in 1 visit., Design, Setting, and Participants: This cohort study examined the implementation of a government-led cervical cancer screening program conducted from January 1, 2016, to December 31, 2020, in Ordos City, China. Female residents, aged 35 to 64 years, who understood the screening procedures and voluntarily participated were included in the study. Women were excluded if they reported never having had sexual intercourse, were pregnant, had a hysterectomy, or had ever undergone treatment for cervical lesions. Statistical analysis was conducted from December 2022 to December 2023., Exposures: The program used the careHPV DNA assay as the primary screening method, and immediate triage was performed by visual inspection if HPV screening results were positive, with a 5-year screening interval. A colposcopy was performed for the women who had suspected cancer on visual inspection results or who were HPV positive and had abnormal visual inspection results, all in 1 visit., Main Outcomes and Measures: The rate of compliance with colposcopy and the detection rate of cervical intraepithelial neoplasia grade 2 or higher (CIN2+)., Results: The study included 187 863 women (median age, 46 years [IQR, 40-52 years]) who participated in the program and had valid HPV test results. The overall prevalence of HPV positivity was 12.8% (24 070 of 187 863), and the adherence to triage with visual inspection among HPV-positive women was 93.9% (22 592 of 24 070). Among HPV-positive women, the rate of compliance with colposcopy was 65.6% (2714 of 4137), and the CIN2+ detection rate was 2.8% (643 of 22 592)., Conclusions and Relevance: The findings of this cohort study suggest that the implementation of HPV testing, visual inspection, and colposcopy within 1 visit may mitigate losses to follow-up, detect precancerous lesions, and hold significant implications for screening in comparable areas with limited health care resources.

Background: The assessment of human papillomavirus (HPV) genotype distribution in terms of age and cervical lesions could contribute to the adoption of more targeted preventive approaches to specific populations against cervical cancer. The current study was conducted in Ordos City, China, with the aim of analyzing the HPV genotypes prevalence and infection patterns within a hospital-based population., Methods: The analysis included a total of 26,692 women aged 25-64 who underwent cervical cancer screening between January 1st, 2019, and June 30th, 2022, in Ordos City. These women had valid results for both the polymerase chain reaction (PCR)-reverse dot blot (RDB) HPV test and the liquid-based cytology (thinprep cytologic test/TCT). Data were extracted from the database of KingMed Diagnostics laboratories. The prevalence of HPV genotypes within different age groups and cytology diagnoses were calculated., Results: Among 26,692 women, 7136 (26.73%) women were HPV positive, 5696 (21.34%) women were high-risk HPV (HR-HPV) positive, and 2102 (7.88%) women had multiple HPV infections. The most frequently detected HPV genotypes were HPV16 (4.72%) and HPV52 (4.15%), ranking as the first and second most prevalent genotypes, respectively. The prevalence of HR-HPV increased with age groups and severity of cervical lesions. Notably, the positive rate of HR-HPV among women aged 35-64 years showed a decreasing trend over the respective years, ranging from 26.00 to 19.70% (P trend  < 0.001)., Conclusion: In conclusion, the epidemiology of HPV genotypes partly reflects the effectiveness of regional cervical cancer prevention and control efforts in the past. These findings can inform future initiatives concerning HPV vaccination and screening in the region., (© 2024. The Author(s).)

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: Cervical squamous intraepithelial lesion (SIL) and cervical cancer are major threats to females' health and life in China, and we aimed to estimate the economic burden associated with their diagnosis and treatment., Methods: A nationwide multicenter, cross-sectional, hospital-based survey was conducted in 26 qualified hospitals across seven administrative regions of China. We investigated females who had been pathologically diagnosed with SIL and cervical cancer, and included five disease courses ("diagnosis", "initial treatment", "chemoradiotherapy", "follow-up" and "recurrence/progression/metastasis") to estimate the total costs. The median and interquartile range (IQR) of total costs (including direct medical, direct non-medical, and indirect costs), reimbursement rate by medical insurance, and catastrophic health expenditures in every clinical stage were calculated., Results: A total of 3,471 patients in different clinical stages were analyzed, including low-grade SIL (LSIL) (n=549), high-grade SIL (HSIL) (n=803), cervical cancer stage IA (n=226), IB (n=610), IIA (n=487), IIB (n=282), III (n=452) and IV (n=62). In urban areas, the estimated total costs of LSIL and HSIL were [Formula: see text]1,637.7 (IQR: [Formula: see text]956.4-[Formula: see text]2,669.2) and [Formula: see text]2,467.1 (IQR: [Formula: see text]1,579.1-[Formula: see text]3,762.3), while in rural areas the costs were [Formula: see text]459.0 (IQR: [Formula: see text]167.7-[Formula: see text]1,330.3) and [Formula: see text]1,230.5 (IQR: [Formula: see text]560.6-[Formula: see text]2,104.5), respectively. For patients with cervical cancer stage IA, IB, IIA, IIB, and III-IV, the total costs were [Formula: see text]15,034.9 (IQR: [Formula: see text]11,083.4-[Formula: see text]21,632.4), [Formula: see text]19,438.6 (IQR: [Formula: see text]14,060.0-[Formula: see text]26,505.9), [Formula: see text]22,968.8 (IQR: [Formula: see text]16,068.8-[Formula: see text]34,615.9), [Formula: see text]26,936.0 (IQR: [Formula: see text]18,176.6-[Formula: see text]41,386.0) and [Formula: see text]27,332.6 (IQR: [Formula: see text]17,538.7-[Formula: see text]44,897.0), respectively. Medical insurance covered 43%-55% of direct medical costs for cervical cancer patients, while the coverage for SIL patients was 19%-43%. For most cervical cancer patients, the expense was catastrophic, and the extent of catastrophic health expenditure was about twice large for rural patients than that for urban patients in each stage., Conclusions: The economic burden of SIL and cervical cancer in China is substantial, with a significant proportion of the costs being avoidable for patients with LSIL. Even for those with medical insurance, catastrophic health expenditures are also a major concern for patients with cervical cancer, particularly for those living in rural areas., (Copyright ©2023 Chinese Journal of Cancer Research. All rights reserved.)

Cervical cancer is a major public health concern in China, accounting for almost one-fifth of the global incidence and mortality. The recently prequalified domestic bivalent human papillomavirus (HPV) vaccine offers a practical and feasible preventive measure. In response to the global call for action, the National Health Commission issued an Action Plan to eliminate cervical cancer by 2030, with promotion of the HPV vaccination for school-aged girls as a critical step. Despite this, implementation of the vaccination has been patchy, with very low coverage among eligible girls. To address this, from December 2021 to December 2022, a demonstration project was launched in Shenzhen, Guangdong Province, to promote the inclusion of HPV vaccine in local immunisation programme and to address existing barriers to implementation. Using multiple sources of data, this article presents a case study of the demonstration project, analysing its impact on rolling out HPV vaccination among eligible girls and identifying any challenges encountered during implementation. The demonstration project has shown promising results in increasing the HPV vaccination rate, promoting public awareness and acceptance of the domestic HPV vaccine, and establishing a model for quickly scaling up the vaccination at the municipal level. The success of the project can be attributed to several factors, including strong governmental commitment, sufficient funding, multi-sectoral collaboration, ensured vaccine accessibility and affordability, improved vaccination services, and effective health education and communication strategies. Lessons learned from Shenzhen can provide valuable insights for future advocacy and implementation of the vaccination in other areas of China, but challenges must be addressed to achieve universal coverage. These include addressing vaccine hesitancy, expanding the programme to cover a broader age range, and ensuring consistent quality of vaccination services in primary care facilities. Overcoming these challenges will require innovative strategies, public-private partnerships, and sustained funding and resources. Future research should focus on evaluating the long-term effectiveness of the vaccination programme and identifying contextual factors that may impact its implementation in different settings. Overall, the effective control of cervical cancer in China will rely on the "political will" to ensure the incorporation of preventive interventions into policies and universal programme coverage., (© 2023. The Author(s).)

We review developments in molecular triaging options for women who test positive for high-risk human papillomavirus (hrHPV) on self-collected samples in the context of cervical cancer elimination. The World Health Organization (WHO) recommends hrHPV screening as the primary test for cervical screening due to its high sensitivity compared to other screening tests. However, when hrHPV testing is used alone for treatment decisions, a proportion of women of childbearing age receive unnecessary treatments. This provides the incentive to optimize screening regimes to minimize the risk of overtreatment in women of reproductive age. Molecular biomarkers can potentially enhance the accuracy and efficiency of screening and triage. HrHPV testing is currently the only screening test that allows triage with molecular methods using the same sample. Additionally, offering self-collected hrHPV tests to women has been reported to increase screening coverage. This creates an opportunity to focus health resources on linking screen-positive women to diagnosis and treatment. Adding an additional test to the screening algorithm (a triage test) may improve the test's positive predictive value (PPV) and offer a better balance of benefits and risks for women. Conventional triage methods like cytology and visual inspection with acetic acid (VIA) cannot be performed on self-collected samples and require additional clinic visits and subjective interpretations. Molecular triaging using methods like partial and extended genotyping, methylation tests, detection of E6/E7 proteins, and hrHPV viral load in the same sample as the hrHPV test may improve the prediction of cervical intraepithelial neoplasia grade 2 or worse (CIN2+) and invasive cancer, offering more precise, efficient, and cost-effective screening regimes. More research is needed to determine if self-collected samples are effective and cost-efficient for diverse populations and in comparison to other triage methods. The implementation of molecular triaging could improve screening accuracy and reduce the need for multiple clinical visits. These important factors play a crucial role in achieving the global goal of eliminating cervical cancer as a public health problem., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Taghavi, Zhao, Downham, Baena and Basu.)

Rationale and Objectives: This study assessed the role of second-look automated breast ultrasound (ABUS) adjunct to mammography (MAM) versus MAM alone in asymptomatic women and compared it with supplementing handheld ultrasound (HHUS)., Materials and Methods: Women aged 45 to 64 underwent HHUS, ABUS, and MAM among six hospitals in China from 2018 to 2022. We compared the screening performance of three strategies (MAM alone, MAM plus HHUS, and MAM plus ABUS) stratified by age groups and breast density. McNemar's test was used to assess differences in the cancer detection rate (CDR), the false-positive biopsy rate, sensitivity, and specificity of different strategies., Results: Of 19,171 women analyzed (mean [SD] age, 51.54 [4.61] years), 72 cases of breast cancer (3.76 per 1000) were detected. The detection rates for both HHUS and ABUS combined with MAM were statistically higher than those for MAM alone (all p < 0.001). There was no significant difference in cancer yields between the two integration strategies. The increase in CRD of the integrated strategies was higher in women aged 45-54 years with denser breasts compared with MAM alone (all p < 0.0167). In addition, the false-positive biopsy rate of MAM plus ABUS was lower than that of MAM plus HHUS (p = 0.025). Moreover, the retraction in ABUS was more frequent in cases detected among MAM-negative results., Conclusion: Integrated ABUS or HHUS into MAM provided similar CDRs that were significantly higher than those for MAM alone in younger women (45-54 years) with denser breasts. ABUS has the potential to avoid unnecessary biopsies and provides specific image features to distinguish malignant tumors from HHUS., Competing Interests: Declaration of Competing Interest None., (Copyright © 2023 The Association of University Radiologists. Published by Elsevier Inc. All rights reserved.)

Introduction: The pivotal efficacy study assessed efficacy and safety of GSK's AS04-HPV-16/18 vaccine in Chinese women aged 18-25 years up to 6 years. The present extension study, performed 4 years later, offered AS04-HPV-16/18 vaccination to placebo recipients. Vaccine safety and its long-term protective effect were assessed at Year 10., Methods: All 6051 women who received AS04-HPV-16/18 or the placebo during the initial study (NCT00779766) were invited to phase III/IV, open-label, partially controlled extension Year 10 study (NCT03629886). Placebo recipients were offered three-dose AS04-HPV-16/18 vaccination and followed up over 12 months to assess the safety. Cervical samples from all women were examined. Vaccine efficacy (VE) against incident infections and cytological lesions associated with HPV-16/18 and other oncogenic types was assessed as exploratory objective., Results: Among 3537 women (out of 6051) enrolled in the extension study, 1791 women (mean age 32.7 years; standard deviation 1.8 years) received AS04-HPV-16/18 and reported no serious adverse events, potential immune-mediated diseases, or adverse pregnancy outcomes related to vaccination. Among 6051 women, VE against incident HPV-16, -18, and -16/18 infections up to Year 10 was 82.8% (95% confidence interval: 72.5-89.7), 79.8% (64.5-89.2), and 80.8% (72.4-87.0), respectively. VE against HPV-16/18 ASC-US+, CIN1+, and CIN2+ was 92.7% (82.2-97.7), 94.8% (67.4-99.9), and 90.5% (34.6-99.8), respectively., Conclusion: AS04-HPV-16/18 vaccine showed an acceptable safety profile in Chinese women vaccinated at age 26 years or above, and a long-term protection similar to other efficacy trials worldwide., (© 2022 GlaxoSmithKline Biologicals SA. Asia-Pacific Journal of Clinical Oncology published by John Wiley & Sons Australia, Ltd.)

Background: Women with breast cancer and improved survival face some specific quality of life (QOL) issues. Electronic health (eHealth) is a useful tool aiming to enhance health services. However, evidence remains controversial about the effect of eHealth on QOL in women with breast cancer. Another unstudied factor is the effect on specific QOL functional domains. Therefore, we undertook a meta-analysis about whether eHealth could improve the overall and specific functional domains of QOL in women with breast cancer., Methods: PubMed, Cochrane Library, EMBASE, and Web of Science were searched to identify appropriate randomized clinical trials from database inception to March 23, 2022. The standard mean difference (SMD) served as the effect size and the DerSimonian-Laird random effects model was constructed for meta-analysis. Subgroup analyses were conducted according to different participant, intervention, and assessment scale characteristics., Results: We initially identified 1954 articles excluding duplicates and ultimately included 13 of them involving 1448 patients. The meta-analysis revealed that the eHealth group had significantly higher QOL (SMD 0.27, 95% confidence interval [95% CI] 0.13-0.40, p < 0.0001) than the usual care group. Additionally, although not statistically significant, eHealth tended to improve the physical (SMD 2.91, 95% CI -1.18 to 6.99, p = 0.16), cognitive (0.20 [-0.04, 0.43], p = 0.10), social (0.24 [-0.00, 0.49], p = 0.05), role (0.11 [0.10, 0.32], p = 0.32), and emotional (0.18 [0.08, 0.44], p = 0.18) domains of QOL. Overall, consistent benefits were observed in both the subgroup and pooled estimates., Conclusions: eHealth is superior to usual care in women with breast cancer for improved QOL. Implications for clinical practice should be discussed based on subgroup analysis results. Further confirmation is needed for the effect of different eHealth patterns on specific domains of QOL, which would help improve specific health issues of the target population., (© 2023 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Background: Gynecological cancer will become a more important public health problem in future years but limited evidence on gynecological cancer burden in China., Methods: We extracted age-specific rate of cancer cases and deaths during 2007-2016 from the Chinese Cancer Registry Annual Report, and estimated age-specific population size using the data released by National Bureau of Statistics of China. Cancer burden were calculated by multiplying the rates with the population size. Temporal trends of the cancer cases, incidence, deaths, and mortality during 2007-2016 were calculated by JoinPoint Regression Program, and from 2017 to 2030 were projected by grey prediction model GM (1,1)., Results: In China, total gynecological cancer cases increased from 177,839 to 241,800, with the average annual percentage change of 3.5% (95% CI: 2.7-4.3%) during 2007-2016. Cervical, uterine, ovarian, vulva, and other gynecological cancer cases increased by 4.1% (95% CI: 3.3-4.9%), 3.3% (95% CI: 2.6-4.1%), 2.4% (95% CI: 1.4-3.5%), 4.4% (95% CI: 2.5-6.4%), and 3.6% (95% CI: 1.4-5.9%) respectively. From 2017 to 2030, projected gynecological cancer cases are changing from 246,581 to 408,314. Cervical, vulva and vaginal cancers showed evident upward trend, while uterine and ovarian cancer cases are slightly increasing. The increases for age-standardized incidence rates were similar with that of cancer cases. Temporal trends of cancer deaths and mortality were similar with that of cancer cases and incidence during 2007-2030, except that uterine cancer deaths and mortality were declined., Conclusions: With the aging of population and other increased risk factors, the burden of gynecological cancers in China is likely to be grew rapidly in the future, comprehensive gynecological cancer control should be concerned., (© 2023. The Author(s).)

Background: There are no studies extrapolating the incidence and mortality of cervical cancer in China by comparing incidence and deaths pattern between geographic and age groups., Methods: We applied age-period-cohort models to assess region-level trends in incidence and mortality from 2006 to 2016, with piecewise linear regression in a Bayesian framework to predict these trends to 2030., Results: Between 2006 and 2016, age-standardized incidence rates (ASIR) for females aged 15 to 84 years increased by 3.7% (95% confidence interval, 3.1%-4.3%) annually from 11.01 to 16.41 per 100,000 females in China. In the 25 to 39 age groups, the incidence rates decreased in urban regions and inversely increased in rural regions. The age-standardized mortality rates (ASMR) increased from 3.18 to 4.83, with annual increases of about 3.6% (1.5%-5.8%). From 2017 to 2030, the ASIR is expected to increase from 17.13 (15.91-18.46) to 23.22 (20.02-27.01) by 2.5% per year (P < 0.05). Meanwhile, the average age at diagnosis is predicted to grow from 53.1 to 60.5 years. In the 15 to 54 age groups, the incidence rates decreased in urban regions but increased in rural regions. The ASMR is expected to increase consistently from 4.82 (4.38-5.31) to 9.13 (7.35-11.39) by 5.0% per year (P < 0.05)., Conclusions: Cervical cancer incidence and mortality rates are projected to increase in China. In addition, the urban-rural incidence gap is estimated to widen further among young women., Impact: Cervical cancer prevention should consider the trend and diversity in incidence patterns between urban and rural regions., (©2023 American Association for Cancer Research.)

No research has been conducted to explore the variables associated with healthcare providers' (HCPs) knowledge and attitudes toward the human papillomavirus vaccine (HPV) since the vaccine was approved for free use in some Chinese cities. In Shenzhen, southern China, a convenience sample strategy was used to distribute questionnaires to HCPs involved in the government's HPV vaccination program from Shenzhen. There were 828 questionnaires collected in total, with 770 used in the analysis. The mean HPV and HPV vaccine knowledge score was 12.0 among HCPs involved in the government HPV vaccination program (with a total score of 15). the average scores for HPV and HPV vaccine knowledge varied among different types of medical institutions. District hospitals had the highest mean score of 12.4, while private hospitals ranked fourth with a mean score of 10.9. Multivariate logistic regression results revealed significant disparities in the type of license and after-tax annual income across HCPs ( p < 0.05). The future education and training for HCPs should focus on private community health centers (CHCs), HCPs whose license type is other than a doctor, and HCPs with low after-tax annual income.

Objectives: International students attending universities in the United States may encounter psychological distress related to their adjustment and experiences studying in a new context and seek services from university counseling centers. Many centers use the Counseling Center Assessment of Psychological Symptoms (CCAPS) to measure psychological distress in college counseling centers. However, this scale has not been tested for measurement invariance with international students. Our purpose was to explore the measurement invariance of the CCAPS-62 and -34 for international students., Methods: We tested measurement invariance for both versions of the scale using data from over 107,000 university students in psychotherapy at university counseling centers. We also examined construct validity and internal consistency., Results: Invariance testing indicated the measurement models of the CCAPS-62 and -34 are equivalent between both groups., Conclusion: These findings are discussed in light of utilizing this widely-used scale in United States university/college counseling centers with international student clients., (© 2022 Wiley Periodicals LLC.)

Background: Current uptake of HPV vaccination and screening in China is far below World Health Organization 2030 targets for cervical cancer elimination. We quantified health and economic losses of delaying large-scale HPV vaccination and screening implementation in China., Methods: We used a previously validated transmission model to project lifetime health benefits, costs, effectiveness, and timeline for cervical cancer elimination of alternative scenarios, including combining HPV vaccination initiated from 2022 to 2030 with screening in different modalities and coverage increase rates, as well as screening alone. All women living or projected to be born in China during 2022-2100 were considered. We employed a societal perspective., Findings: Regardless of vaccine type, immediate large-scale vaccination initiated in 2022 and achieving 70% coverage of HPV-based screening in 2030 (no-delay scenario) would be the least costly and most effective. Compared with the no-delay scenario, delaying vaccination by eight years would result in 434,000-543,000 additional cervical cancer cases, 138,000-178,000 deaths, and $2863-4437 million costs, and delay elimination by 9-10 years. Even with immediate vaccination, the gradual scale-up of LBC-based screening to 70% coverage in 2070 would result in 2,530,000-3,060,000 additional cases, 909,000-1,040,000 deaths, and $5098-5714 million costs compared with no-delay scenario, and could not achieve elimination if domestic 2vHPV or 4vHPV vaccines are used (4.09-4.21 cases per 100,000 woman in 2100)., Interpretation: Delaying large-scale HPV vaccination and/or high-performance screening implementation has detrimental consequences for cervical cancer morbidity, mortality, and expenditure. These findings should spur health authorities to expedite large-scale vaccine rollout and improve screening., Funding: Bill & Melinda Gates Foundation (INV-031449 and INV-003174) and CAMS Innovation Fund for Medical Sciences (CIFMS) (2021-I2M-1-004)., Competing Interests: YQ and FZ report grants from GlaxoSmithKline Biologicals, Merck & Co, and Xiamen Innovax Biotech to their institution, to undertake clinical trials on the human papillomavirus (HPV) vaccine. MJ has previously received research grants (unrelated to this paper) from the Bill & Melinda Gates Foundation, the National Institute for Health Research, Research Councils UK, Gavi, the Vaccine Alliance, the European Commission, and Wellcome Trust. Other co-authors declare no competing interests., (© 2023 The Authors.)

The appropriate management strategies for BI-RADS category 4a lesions among handheld ultrasound (HHUS) remain a matter of debate. We aimed to explore the role of automated breast ultrasound (ABUS) or the second-look mammography (MAM) adjunct to ultrasound (US) of 4a masses to reduce unnecessary biopsies. Women aged 30 to 69 underwent HHUS and ABUS from 2016 to 2017 at five high-level hospitals in China, with those aged 40 or older also accepting MAM. Logistic regression analysis assessed image variables correlated with false-positive lesions in US category 4a. Unnecessary biopsies, invasive cancer (IC) yields, and diagnostic performance among different biopsy thresholds were compared. A total of 1946 women (44.9 ± 9.8 years) were eligible for analysis. The false-positive rate of category 4a in ABUS was almost 65.81% (77/117), which was similar to HHUS (67.55%; 127/188). Orientation, architectural distortion, and duct change were independent factors associated with the false-positive lesions in 4a of HHUS, whereas postmenopausal, calcification, and architectural distortion were significant features of ABUS (all p < 0.05). For HHUS, both unnecessary biopsy rate and IC yields were significantly reduced when changing biopsy thresholds by adding MAM for US 4a in the total population (scenario #1:BI-RADS 3, 4, and 5; scenario #2: BI-RADS 4 and 5) compared with the current scenario (all p < 0.05). Notably, scenario #1 reduced false-positive biopsies without affecting IC yields when compared to the current scenario for ABUS ( p < 0.001; p = 0.125). The higher unnecessary biopsy rate of category 4a by ABUS was similar to HHUS. However, the second-look MAM adjunct to ABUS has the potential to safely reduce false-positive biopsies compared with HHUS.

Background: Age-specific data on anal, and corresponding cervical, human papillomavirus (HPV) infection are needed to inform female anal cancer prevention., Methods: We centrally reanalyzed individual-level data from 26 studies reporting HPV prevalence in paired anal and cervical samples by human immunodeficiency virus (HIV) status and age. For women with HIV (WWH) with anal high-grade squamous intraepithelial lesions or worse (HSIL+), we also investigated concurrent cervical cytopathology., Results: In HIV-negative women, HPV16 prevalence decreased significantly with age, both at anus (4.3% at 15-24 years to 1.0% at ≥55 years; ptrend = 0.0026) and cervix (7.4% to 1.7%; ptrend < 0.0001). In WWH, HPV16 prevalence decreased with age at cervix (18.3% to 7.2%; ptrend = 0.0035) but not anus (11.5% to 13.9%; ptrend = 0.5412). Given anal HPV16 positivity, concurrent cervical HPV16 positivity also decreased with age, both in HIV-negative women (ptrend = 0.0005) and WWH (ptrend = 0.0166). Among 48 WWH with HPV16-positive anal HSIL+, 27 (56%) were cervical high-risk HPV-positive, including 8 with cervical HPV16, and 5 were cervical HSIL+., Conclusions: Age-specific shifts in HPV16 prevalence from cervix to anus suggest that HPV infections in the anus persist longer, or occur later in life, than in the cervix, particularly in WWH. This is an important consideration when assessing the utility of cervical screening results to stratify anal cancer risk., Competing Interests: Potential conflicts of interest. A. P. O. reports grants made to her institutions from AMC, grant no. 2UM1CA121947 and an UPR/MDACC Partnership grant no. 2U54CA096297 for time and effort support to the present manuscript. She reports NIH grants not related to the current work. She reports consulting fees and payment for lectures from Merck and Co. R. K. was supported by the Canadian Institutes of Health Research (CIHR) for the present manuscript. A. d. P. shared data from the EVVA study for this manuscript. The EVVA study was supported by the CIHR, and the AIDS and Infectious Diseases Network of Fonds de Recherche du Quebec Sante. Payments were made to A. d. P.’s institution. J. M. P. reports grants and personal fees from Merck and Co.; consulting fees from Vir Biotechnology, Antiva Biosciences, and Virion Therapeutics; personal fees Janssen Pharmaceuticals; stock or stock options from Virion Therapeutics and Vir Biotechnology (outside the submitted work); and a leadership role in the International Papillomavirus Society. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2022. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Background: A key barrier to cervical cancer elimination in China is low human papillomavirus (HPV) vaccine uptake, which is limited by supply constraints, high prices, and restriction to two/three-dose schedule. We explored optimal vaccination strategies for maximizing health and economic benefits accommodated to different supply and dose schedules., Methods: We evaluated different HPV vaccine strategies under 4 scenarios with different assumptions about vaccine availability and dose schedules. Each strategy involved different vaccine types, target ages, and modes of delivery. We used a previously validated transmission model to assess the health impact (cervical cancer cases averted), efficiency (number of doses needed to be given to prevent one case of cervical cancer [NND]), and value for money (incremental cost-effectiveness ratio [ICER] and return on investment [ROI]) of different strategies in Chinese females over a 100-year time horizon. All costs are expressed in 2021 dollars. We adopted a societal perspective and discounted quality-adjusted life-years (QALYs), costs and benefits by 3% annually for cost-effectiveness analysis and ROI calculation., Findings: In a supply-constrained and on-label use scenario, compared with no vaccination, two-dose routine vaccination of 14-year-olds would be the optimal, cost-saving strategy for a future national program (NNDs: 150-220, net cost saving: $15 164 million-$22 034 million, ROIs: 7-14, depending on vaccine type). If the one-dose schedule recommended by WHO is permitted in China, then reallocating the second dose from the routine cohorts to add a catch-up vaccination at 20-year-olds would be the most efficient strategy (NNDs: 73-107), and would be cost-saving compared with routine one-dose vaccination only (net cost saving: $4127 million-$6035 million, ROIs: 19-37). When supply constraints are lifted, scaling up vaccination in older females to 26 years could further expand the health benefits and still be cost-saving compared to maintaining the optimal vaccination strategy in the supply-constrained context., Interpretation: Our study provides timely evidence for the current and future HPV vaccination strategy planning in China, and may also be of value to other countries with supply and dose restrictions., Funding: Bill & Melinda Gates Foundation; CAMS Innovation Fund for Medical Sciences (CIFMS)., Competing Interests: YQ and FZ report grants from GlaxoSmithKline Biologicals, Merck & Co, and Xiamen Innovax Biotech to their institution, to undertake clinical trials on the human papillomavirus (HPV) vaccine. Other co-authors declare no competing interests., (© 2022 The Author(s).)

The World Health Organization (WHO) global strategy to eliminate cervical cancer (CxCa) could result in &gt;62 million lives saved by 2120 if strategy targets are reached and maintained: 90% of adolescent girls receiving prophylactic human papillomavirus (HPV) vaccine, 70% of women receiving twice-lifetime cervical cancer screening, and 90% of cervical pre-cancer lesions and invasive CxCa treated. However, the cost and complexity of CxCa screening and treatment approaches has hampered scale-up, particularly in low- and middle-income countries (LMICs), and new approaches are needed. Therapeutic HPV vaccines (TxV), which could clear persistent high-risk HPV infection and/or cause regression of pre-cancerous lesions, are in early clinical development and might offer one such approach. During October 2021 to March 2022, WHO, in collaboration with the Bill and Melinda Gates Foundation, convened a series of global expert consultations to lay the groundwork for understanding the potential value of TxV in the context of current CxCa prevention efforts and for defining WHO preferred product characteristics (PPCs) for TxV. WHO PPCs describe preferences for vaccine attributes that would help optimize vaccine value and use in meeting the global public health need. This paper reports on the main discussion points and findings from the expert consultations. Experts identified several ways in which TxV might address challenges in current CxCa prevention programmes, but emphasized that the potential value of TxV will depend on their degree of efficacy and how quickly they can be developed and implemented relative to ongoing scale-up of existing interventions. Consultation participants also discussed potential use-cases for TxV, important PPC considerations (e.g., vaccine indications, target populations, and delivery strategies), and critical modelling needs for predicting TxV impact and cost-effectiveness., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: From the full list of authors, the following have declared potential conflicts of interest; Celina Schocken is currently conducting consultation work on HPV diagnostics for Roche Diagnostics; Margaret Stanley has provided consultancy services for Merck Pharmaceuticals. Karen Canfell, who is leading the modelling effort for this work is Co-principal investigator (Co-PI) on a cervical cancer trial, funded by VCS (a non-profit foundation) which is also supported by Roche Diagnostics. She also acts as Co-PI for a study on the elimination of CxCa, which is supported by Minderoo Foundation Frazer Family Foundation, which is supplied with equipment and donations from Cepheid Inc. Gina Ogilvie, as part of a regulatory, legislative or judicial process has provided expert opinion or testimony related to the subject of the meetings and work for a commercial entity (not specified), and in addition has held office or other position in which she has represented interests or defended a position relating to the subject matter (unspecified). Luisa Lina Villa provides consultancy services and has spoken on behalf of Merck Pharmaceuticals on the topic of prophylactic HPV vaccines. All participants in the Therapeutic HPV Vaccine PPC Expert Consultations completed WHO Declaration of Interests statements, and their participation in these meetings and commenting on aspects of the PPC development were in accordance with the Organization’s guidelines for Declaration of Interests for WHO experts. Where authors are identified as personnel of the International Agency for Research on Cancer/World Health Organization, the authors alone are responsible for the views expressed in this article and they do not necessarily represent the decisions, policy or views of the International Agency for Research on Cancer/World Health Organization., (Copyright © 2022. Published by Elsevier Ltd.)

Triaging of women positive for high-risk human papillomavirus (hrHPV) on self-collected samples requires a molecular reflex test to avoid recall for cytology or visual tests. We assessed triage performance and predictive value of human gene methylation panel (ZNF671/ASTN1/ITGA4/RXFP3/SOX17/DLX1) alone and with combination of HPV16/18 genotyping in a longitudinal screening study. Out of 9526 women at baseline, 1758 women positive for hrHPV on self-collected samples followed up yearly were included in the current analysis. Satisfactory risk stratification to detect cervical intraepithelial neoplasia grade 2 or worse (CIN2+) was demonstrated by the methylation panel with an odds ratio (OR) of 11.3 among methylation-positive women compared to methylation-negative counterparts. Triaging with methylation panel reduced colposcopy referral rate by 67.2% with sensitivity and specificity of 83.0% and 69.9% to detect CIN2+. The corresponding values for the combining methylation and HPV 16/18 were 96.6% and 58.3%. The cumulative 3-year incident CIN2+ risk was 6.8% (95% CI: 4.9%-8.6%) for hrHPV positive women, which was reduced to 4.5% (95% CI: 2.7%-6.3%) and 2.9% (95% CI: 1.2%-4.5%) for women negative on methylation triaging alone and negative on the combined strategy. The corresponding risk for women positive for both methylation and HPV 16/18 reached 33.7% (95% CI: 19.0%-45.8%). Our study demonstrated the satisfactory triage performance and predictive value of the methylation panel, especially in combination with HPV 16/18 genotyping. The substantially lower risk of CIN2+ among the triage negative women over the next 3 years suggests that the interval for repeat HPV test can be safely extended to at least 2 years., (© 2022 UICC.)

Objective: We assessed the longitudinal risk of developing cervical intraepithelial neoplasia (CINs) with self-sampling human papillomavirus (HPV) tests, based on polymerase chain reaction (PCR) and signal amplification ( care HPV), to explore the appropriate intervals for cervical cancer screening., Methods: A prospective study was conducted in China during 2017-2020. Participants were invited for PCR and care HPV tests with self-samples at baseline. Women positive in either HPV test underwent colposcopy and biopsy if necessary. Women with baseline CIN grade one (CIN1) or less were followed up over 3 years. The absolute risk was assessed by the immediate risk (IR) and cumulative risk (CR), and the relative risk was assessed by the hazard ratio (HR) with a 95% confidence interval (CI)., Results: A total of 8,126 women were included in the final analysis. Women positive for the PCR HPV test had comparable IRs of CIN2+ and CIN3+ to those positive on the care HPV test. With triage by HPV genotyping, women with HPV 16/18 infection had the highest IRs of CIN2+ (21.15%) and CIN3+ (9.67%). For CR, women negative for PCR HPV test had a lower risk of CIN2+ than that reported in women negative on care HPV test (0.57% versus 0.98%, HR = 0.58, 95% CI: 0.38, 0.87), but no significant difference was found in the CRs of CIN3+ between them (0.25% versus 0.39%, HR = 0.64, 95% CI: 0.34, 1.20). Among women with CIN1 or less at baseline, women who were persistent or recurrent positive on care HPV or PCR HPV test had a higher risk of developing CIN3+ (11.36%-14.59%), compared with women remained HPV negative from baseline throughout follow-up (≤0.28%)., Conclusions: Routine screening with 3-year intervals is acceptable for self-sampling HPV tests based on PCR or care HPV test. Women positive on HPV16/18 triaging at baseline or with CIN1 or less at baseline while being persistent or recurrent positive on care HPV or PCR HPV test during 3-year follow-up require immediate colposcopy or treatment., Competing Interests: The authors declare that they have no conflict of interests., (© 2022 Chinese National Cancer Center. Published by Elsevier B.V.)

Objectives: Breast cancer screening guidelines could provide valuable tools for clinical decision making by reviewing the available evidence and providing recommendations. Little information is known about how many countries have issued breast cancer screening guidelines and the differences among existing guidelines. We systematically reviewed current guidelines and summarized corresponding recommendations, to provide references for good clinical practice in different countries., Methods: Systematic searches of MEDLINE, EMBASE, Web of Science, and Scopus from inception to March 27th, 2021 were conducted and supplemented by reviewing the guideline development organizations. The quality of screening guidelines was assessed from six domains of the Appraisal of Guidelines for Research and Evaluation Ⅱ (AGREE Ⅱ) instrument by two appraisers. The basic information and recommendations of the issued guidelines were extracted and summarized., Results: A total of 23 guidelines issued between 2010 and 2021 in 11 countries or regions were identified for further review. The content and quality varied across the guidelines. The average AGREE Ⅱ scores of the guidelines ranged from 33.3% to 87.5%. The highest domain score was "clarity of presentation" while the domain with the lowest score was "applicability". For average-risk women, most of the guidelines recommended mammographic screening for those aged 40-74 years, specifically, those aged 50-69 years were regarded as the optimal age group for screening. Nine of 23 guidelines recommended against an upper age limit for breast cancer screening. Mammography (MAM) was recommended as the primary screening modality for average-risk women by all included guidelines. Most guidelines suggested annual or biennial mammographic screening. Risk factors of breast cancer identified in the guidelines mainly fell within five categories which could be broadly summarized as the personal history of pre-cancerous lesions and/or breast cancer; the family history of breast cancer; the known genetic predisposition of breast cancer; the history of mantle or chest radiation therapy; and dense breasts. For women at higher risk, there was a consensus among most guidelines that annual MAM or annual magnetic resonance imaging (MRI) should be given, and the screening should begin earlier than the average-risk group., Conclusions: The majority of 23 included international guidelines were issued by developed countries which contained roughly the same but not identical recommendations on breast cancer screening age, methods, and intervals. Most guidelines recommended annual or biennial mammographic screening between 40 and 74 years for average-risk populations and annual MAM or annual MRI starting from a younger age for high-risk populations. Current guidelines varied in quality and increased efforts are needed to improve the methodological quality of guidance documents. Due to lacking clinical practice guidelines tailored to different economic levels, low- and middle-income countries (LMICs) should apply and implement the evidence-based guidelines with higher AGREE Ⅱ scores considering local adaption., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Objectives: To explore the prevalence and risk factors of anogenital human papillomavirus (HPV) infection and neoplasia among women living with HIV (WLHIV) in China., Methods: A cross-sectional survey was conducted from 2019 to 2020, 409 WLHIV aged 18 years and older were recruited from an HIV treatment clinic in Yunnan, China. Cervical and anal samples were collected for HPV testing of 15 HPV genotypes and cytological interpretation. Women positive for cervical HPV or cytological abnormalities were recalled for colposcopy examination and biopsy when necessary. Prevalence of anogenital HPV infection and neoplasia were compared by logistic regression., Results: HPV prevalence was 34.2% (140/409) for cervical and 34.7% (142/409) for anal (high-risk HPV being 30.6% (125/409) and 30.3% (124/409), respectively). The most frequent genotypes were HPV-52, HPV-16 and HPV-58 in the cervix, HPV-52, HPV-53 and HPV-39 in the anus, with strong correlation between cervical and anal positivity, both overall and at a type-specific level. Cervical HPV was most associated with short duration of combination antiretroviral therapies (cART) (≤2 vs >2 years, adjusted OR (aOR)=2.25, 95% CI: 1.22 to 4.12) and high initial HIV viral load (≥1000 vs <1000 copies/mL, aOR=1.98, 95% CI: 1.10 to 3.58). Anal HPV was most associated with low nadir CD4 count (<200 vs ≥200 cells/µL, aOR=1.80, 95% CI: 1.01 to 3.22) and low current CD4 count (<350 vs ≥500 cells/µL, aOR=2.06, 95% CI: 1.00 to 4.36). CIN2+ prevalence was 4.6% and associated with low nadir CD4 count (aOR=4.63, 95% CI: 1.24 to 17.25)., Conclusions: Cervical and anal HPV were strongly correlated and, together with associated neoplasia, were highly prevalent among WLHIV in China. Early initiation of cART to avoid severe immunodeficiency should decrease anogenital HPV prevalence and related cancer burden among WLHIV. Incorporating anogenital cancer prevention services into HIV/AIDS care is warranted., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: We aim to evaluate the morbidity and mortality of cancer attributable to human papillomavirus (HPV) infection in China in 2016. Methods: Based on the cancer incidence and mortality rates, national population data, and population attributable fraction ( PAF ) in China, we calculated the number of incidence and death cases attributed to HPV infection in different areas, age groups, and gender in China in 2016. The standardized incidence and mortality rates for cancer attributed to HPV infection were calculated by using Segi's population. Results: In 2016, a total of 124 772 new cancer cases (6.32 per 100 000) were attributed to HPV infection in China, including 117 118 cases in women and 7 654 cases in men. Of these cancers, cervical cancer was the most common one, followed by anal cancer, oropharyngeal cancer, penile cancer, vaginal cancer, laryngeal cancer, oral cancer, and vulvar cancer. A total of 41 282 (2.03 per 100 000) deaths were attributed to HPV infection, of which 37 417 occurred in women and 3 865 in men. Most deaths were caused by cervical cancer, followed by anal cancer, oropharyngeal cancer, penile cancer, laryngeal cancer, vaginal cancer, oral cancer, and vulvar cancer. The incidence and mortality rates of cervical cancer increased rapidly with age, peaked in age group 50-54 years, then decreased obviously. The morbidity and mortality rates of non-cervical cancer increased with age. The cancer case and death numbers in rural areas (57 089 cases and 19 485 deaths) were lower than those in urban areas (67 683 cases and 21 797 deaths). However, the age-standardized incidence rate (ASIR) and age-standardized mortality rate (ASMR) of cervical cancer were higher in rural areas than in urban areas. There were no significant differences in ASIR and ASMR of non-cervical cancers between urban areas and rural areas. Conclusions: The incidence of cancers attributed to HPV infection in China was lower than the global average, but the number of incidences accounted largely, furthermore there is an increasing trend of morbidity and mortality. The preventions and controls of cervical cancer and male anal cancer are essential to contain the increases in cancer cases and deaths attributed to HPV infection.

Background: Information on temporal trends of cancer attributable to human papillomavirus (HPV) in China is limited., Methods: Cancer incidence and mortality during 2007 to 2015 were extracted from the Chinese Cancer Registry Annual Report and the national population from the National Bureau of Statistics. HPV-attributable cancer burden and the average annual percentage change during 2007 to 2015 were estimated and cancer burden during 2016 to 2030 was projected., Results: HPV-attributable cancer cases have increased by 3.8% [95% confidence interval (CI), 2.9%-4.8%] annually from 85,125 to 113,558 and age-standardized incidence rate (ASIR) rose by 3.0% (95% CI, 2.5%-3.5%) from 4.67 to 5.83 per 100,000 persons during 2007 to 2015. Cervical, female anal, and vulva cancer cases have increased by 3.8% (95% CI, 2.8%-4.7%), 6.5% (95% CI, 1.2%-12.2%), and 3.7% (95% CI, 1.6%-5.8%) per year. Male anal and oropharyngeal cancer cases have elevated by 7.5% (95% CI, 2.8%-12.5%) and 4.4% (95% CI, 2.4%-6.3%) annually. The increases of cervical and anal cancer were most rapid among those aged 50 and older. HPV-attributable cancer deaths and mortality rate have risen by 4.7% (95% CI, 2.9%-6.7%) and 3.3% (95% CI, 0.9%-5.8%) respectively. HPV-attributable cancer cases and ASIR are projected to reach 214,077 and 9.35 of 100,000 persons by 2030 respectively, with 87.7% being cervical cancer, and anal cancer cases are expected to triple., Conclusions: HPV-attributable cancer burden has largely increased in the past and will keep rising for the next decade. Cervical cancer control should be the priority and anal cancer prevention should be addressed., Impact: This study supplies fundamental evidence for policy-making on HPV-attributable cancer control., (©2022 American Association for Cancer Research.)

Background: Cervical cancer is a significant public health problem, with 570,000 new cases and 300,000 deaths of women per year globally, mostly in low- and middle-income countries. In 2018 the WHO Director General made a call to action for the elimination of cervical cancer as a public health problem., Main Body: New thinking on programmatic approaches to introduce emerging technologies and screening and treatment interventions of cervical precancer at scale is needed to achieve elimination goals. Implementation research (IR) is an important yet underused tool for facilitating scale-up of evidence-based screening and treatment interventions, as most research has focused on developing and evaluating new interventions. It is time for countries to define their specific IR needs to understand acceptability, feasibility, and cost-effectiveness of interventions as to design and ensure effective implementation, scale-up, and sustainability of evidence-based screening and treatment interventions. WHO convened an expert advisory group to identify priority IR questions for HPV-based screening and treatment interventions in population-based programmes. Several international organizations are supporting large scale introduction of screen-and-treat approaches in many countries, providing ideal platforms to evaluate different approaches and strategies in diverse national contexts., Conclusion: For reducing cervical cancer incidence and mortality, the readiness of health systems, the reach and effectiveness of new technologies and algorithms for increasing screening and treatment coverage, and the factors that support sustainability of these programmes need to be better understood. Answering these key IR questions could provide actionable guidance for countries seeking to implement the WHO Global Strategy towards cervical cancer elimination., (Copyright © 2021. Published by Elsevier Inc.)

Multiple barriers impede the transformation of evidence-based research into implementation of cervical cancer screening in ASEAN countries. This review is the first of its kind to show the disease burden of cervical cancer, progress till date to implement screening and corresponding challenges, and propose tailored solutions to promote cervical cancer prevention in ASEAN. In 2020, approximately 69 000 cervical cancer cases and 38 000 deaths happened in ASEAN, and more than 44% and 63% increases on new cases and deaths are expected in 2040. Only four countries have initiated population-based cervical cancer screening programs, but the participation rate is less than 50% in some countries and even lower than 10% in Myanmar and Indonesia. Inequity and unavailability in service delivery, lack of knowledge and awareness, limited follow-up and treatment capacity, and funding sustainability affect successful scale-up of cervical cancer screening most in ASEAN. Implementing HPV detection-based primary screening, appropriate management of screen-positives, enhancing health education, integrating health services can accelerate reduction of cervical cancer burden in ASEAN. Achieving high screening coverage and high treatment compliance will help ASEAN countries remain aligned to cervical cancer elimination strategies., (Copyright © 2021 Elsevier B.V. All rights reserved.)

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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Given that only a small percentage of human papillomavirus (HPV)-positive women develop cancer, HPV is necessary but insufficient for carcinogenesis. Mucosally transmitted viral cofactors appear to contribute to HPV-related cervical cancer, such as Epstein-Barr virus (EBV), but previous studies have shown inconsistent outcomes. The exact role of EBV in cervical cancer remains unclear, and more studies are needed to determine its involvement. In this study, we describe the prevalence of EBV and HPV coinfection in HIV-positive women and explore how abnormal host immune status induced by viral coinfections modulates epithelial gene expression. We found a significant correlation between EBV-HPV coinfection and the incidence of high-grade cervical intraepithelial neoplasia (CIN2+). RNA sequencing indicated that CIN tissues coinfected with EBV and HPV led to significant changes in the gene expression of epithelial differentiation and development compared to normal tissues with HPV infection alone. In particular, several differentially expressed genes (DEGs) are closely associated with cancer, such as CACNG4, which was confirmed to be upregulated at both the mRNA and protein levels. Therefore, these findings provide some evidence that EBV may act as a cofactor or mediator in HPV-related cervical cancer. Specific genes or proteins, such as CACNG4, may serve as biomarkers that can risk stratify patients based on pathological changes in the cervix., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Feng, Duan, Gao, Zhang, Qiao, Li and Zhao.)

Objectives: To evaluate the clinical performance of liquid-based cytology (LBC), HPV tests and visual inspections with acetic acid or Lugol's iodine (VIA/VILI) as primary screening and triage strategies among Chinese women living with HIV (WLHIV)., Methods: WLHIV aged 18 years and older were recruited from HIV/AIDS treatment clinic in Yunnan, China from 2019 to 2020. Women were screened with self- and physician-sampling for HPV tests, LBC, and VIA/VILI. Women positive for any HPV or with cytological abnormalities were recalled for colposcopy examination and biopsy when necessary. Clinical performance of primary and triage strategies for detecting cervical intraepithelial neoplasia grade 2 or worse (CIN2+) was evaluated., Results: For primary screening, sensitivity of physician-HPV tests was 100%, 89.5%, and 100% for hybrid capture 2 (HC2), cobas, and Sansure HPV, and specificity was 80.4%, 85.1%, and 72.0%, respectively. Self-HPV test achieved considerable performance with physician-HPV. Sensitivity and specificity were 61.1% and 96.3% for LBC (atypical squamous cells of undetermined significance or worse [ASCUS+]), 40.0% and 77.3% for VIA/VILI. For triaging HPV-positive women, LBC (ASCUS+), HPV-16/18 genotyping, and VIA/VILI-elevated specificity with sensitivity declined 30%-50% compared with HPV screening alone. Restricted HPV genotyping triage (HPV-16/18/31/33/45/52/58) demonstrated the optimal accuracy (89.5% sensitivity, 81.9% specificity), and was similar to HPV-16/18 with reflex LBC (ASCUS+). Combination antiretroviral therapies (cARTs) <2 years were associated with decreased specificity of HC2 (aOR: 1.87, 95% CI: 1.22-3.91) and Sansure HPV (2.48, 1.43-4.29)., Conclusions: Self-HPV with restricted genotyping triage is highly recommended for cervical cancer screening for WLHIV in China. Feasible triage to increase HPV specificity among women with short duration of cART is needed., (© 2021 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Background: Although recent studies have suggested that naturally acquired Human papillomavirus (HPV) antibodies are partly protective against subsequent homotypic infection, the extent of protection remains indecisive. Here, we evaluate the protective effect of neutralizing and IgG antibodies simultaneously., Methods: In a cohort of 3634 women aged 18-45 years from the control arm of a phase III trial of the HPV-16/18 bivalent vaccine, participants were tested for neutralizing antibodies by pseudovirion-based neutralization assay (PBNA) and IgG antibodies by enzyme-linked immunosorbent assay (ELISA) at baseline. HPV-16/18 incident and persistent infections were identified using cervical specimens periodically collected during the 5·5 years of follow-up. The protective effects of HPV-16/18 neutralizing and IgG antibodies against homotypic infection were assessed using a Cox proportional hazard model., Findings: For the persistent infection (PI) endpoints of HPV-16/18 lasting for over 6/12 months, a prevalence of type-specific neutralizing antibodies was highly protective (6-month PI: hazard ratio (HR) = 0·16, 95% confidence interval (CI): 0·04, 0·65; 12-month PI: HR = 0·23, 95% CI: 0·06, 0·94), whereas a prevalence of IgG antibodies was associated with minor and non-significant protection (6-month PI: HR = 0·66, 95% CI: 0·40, 1·09; 12-month PI: HR = 0·66, 95% CI: 0·36, 1·20). After increasing the cut-off value to the median IgG level, the risk of 6-month PI was significantly lower in seropositive vs seronegative women (HR = 0·38, 95% CI: 0·18, 0·83)., Interpretation: Naturally acquired antibodies are associated with a substantially reduced risk of subsequent homotypic infection., Funding: NSFC; The Fujian Province Health Education Joint Research Project; Xiamen Science and Technology Major Project; CIFMS; and Xiamen Innovax., Competing Interests: Ting Wu reports grants from National Natural Science Foundation of China (Grant number: 82073562). Youlin Qiao reports grants from Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences (Grant number: 2017-I2M-B&R-03 and 2016-I2M-1–019). Jun Zhang reports grants from The Fujian Province Health Education Joint Research Project (Grant number: 2019-WJ-05). Ningshao Xia reports grants from Xiamen Science and Technology Major Project (Grant number: 3502Z20193009), Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences (Grant number: No. 2019RU022), and Xiamen Innovax Biotech Company. Ting Wu, Youlin Qiao, Jun Zhang, Fanghui Zhao, Wen Chen, Chao Zhao, and Lihui Wei report honoraria and travel expenses of invited lectures for educational events from Xiamen Innovax Biotech Company, outside the submitted work. Zhijie Lin, Bizhen Lin and Huirong Pan are employees of Xiamen Innovax Biotech Company. All other authors declare no conflicts of interest., (© 2021 The Author(s). Published by Elsevier Ltd.)

Objective: To measure the rates of adverse obstetric outcomes in spontaneous delivery in a population of young women with high uptake of the bivalent human papillomavirus (HPV) vaccine., Study Design: This was a population-based ecological study with data from the Aberdeen Maternity and Neonatal Databank, UK. All women born between 1986-1996 with spontaneous singleton live birth at age 20-30 years were included for analysis. Exposure was defined according to maternal year of birth and HPV immunisation eligibility: pre-immunisation cohort (1986-1990), catch-up immunisation cohort (1991-1994) and routine immunisation cohort (1995-1996). Outcomes were defined as spontaneous preterm birth (PTB), low birth weight (LBW) and pre-labour preterm rupture of membranes (pPROM). Generalized estimating equation models were applied, adjusted for deprivation, smoking status, marital status, body mass index, parity, maternal age and year of infant delivery., Results: A total of 6515 spontaneous singleton live births were included in final analysis, with 5134 births included in the pre-immunisation cohort, 1250 in the catch-up immunisation cohort and 131 in the routine immunisation cohort. Compared with the pre-immunisation cohort, no statistically significant reduction on PTB, LBW or pPROM were observed in either immunised cohorts. The adjusted odds ratio (aOR) on PTB was 0.64 (95 % confidence interval, 0.40-1.03) in the catch-up cohort and 0.71 (0.28-1.77) in the routine cohort. The corresponding aOR were 0.88 (0.54-1.45) and 0.51 (0.16-1.62) for LBW and 1.62 (0.58-4.54) and 1.51 (0.21-11.01) for pPROM., Conclusions: We did not observe a significant reduction on PTB, LBW or pPROM among spontaneous singleton live birth in either HPV immunised cohorts, although the additional benefit in improving obstetric outcomes cannot be excluded because of the limits of the sample size and the study design. Further demonstration is warranted when more women in the fully HPV immunised cohorts embark on pregnancy., Competing Interests: Declaration of Competing Interest Fanghui Zhao has received grants through her institution from GlaxoSmithKline Biologicals SA, MSD China and Xiamen Innovax Biotech Co, Ltd to undertake clinical trials or studies on HPV vaccine. Others report no conflict of interest., (Crown Copyright © 2021. Published by Elsevier B.V. All rights reserved.)

Since licensure of human papillomavirus (HPV) vaccine in mainland China, little research has been conducted about healthcare providers' (HCPs) understanding and recommendation of HPV vaccine. A multi-stage convenience sample of Chinese HCPs (N = 5270) were surveyed, involving obstetrician-gynecologists, HCPs from Division of Expanded Program on Immunization (DEPI), Community Health Center (CHC) and other non-HPV closely related professions. Binary logistic regression was conducted to explore factors associated with knowledge and recommendation behaviors. Overall, HCPs showed basic HPV/HPV vaccine knowledge with median (interquartile range) score at 9.5 (7.5-11.6) out of 16 and relatively high recommendation behavior (74.8%). Identified knowledge gaps among HCPs included risk factors of HPV infection, best time to vaccinate, prophylactic functions of HPV vaccine and especially classification of low-risk and high-risk types. Profession-specific analysis in individual knowledge item showed HCPs from CHC were suboptimal on HPV while obstetrician-gynecologists were less competent on HPV vaccine knowledge. Obstetrician-gynecologists also recommended vaccination less frequently than HCPs from DEPI and CHC. Besides being key predictors of recommendation practice (2.74, 95% CI: 2.34-3.21), knowledge shared independent determinants with recommendation behavior on age and ethnicity and additionally associated with education and title by itself. Findings highlight overall and profession-specific gaps on HPV and HPV vaccine knowledge and recommendation practice. Future education and training efforts should be profession-niche-targeting and focus much on HCPs with lower title or education background and from minorities., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)