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The microbiome is able to modulate immune responses, alter the physiology of the human organism, and increase the risk of viral infections and development of diseases such as cancer. In this review, we address changes in the cervical microbiota as potential biomarkers to identify the risk of cervical intraepithelial neoplasia (CIN) development and invasive cervical cancer in the context of human papillomavirus (HPV) infection. Current approaches for clinical diagnostics and the manipulation of microbiota with the use of probiotics and through microbiota transplantation are also discussed.

Background The World Health Organization (WHO) called for global action towards the elimination of cervical cancer. One of the main strategies is to screen 70% of women at the age between 35 and 45 years and 90% of women managed appropriately by 2030. So far, approximately 85% of cervical cancers occur in low- and middle-income countries (LMICs). The colposcopy-guided biopsy is crucial for detecting cervical intraepithelial neoplasia (CIN) and becomes the main bottleneck limiting screening performance. Unprecedented advances in artificial intelligence (AI) enable the synergy of deep learning and digital colposcopy, which offers opportunities for automatic image-based diagnosis. To this end, we discuss the main challenges of traditional colposcopy and the solutions applying AI-guided digital colposcopy as an auxiliary diagnostic tool in low- and middle- income countries (LMICs). Main body Existing challenges for the application of colposcopy in LMICs include strong dependence on the subjective experience of operators, substantial inter- and intra-operator variabilities, shortage of experienced colposcopists, consummate colposcopy training courses, and uniform diagnostic standard and strict quality control that are hard to be followed by colposcopists with limited diagnostic ability, resulting in discrepant reporting and documentation of colposcopy impressions. Organized colposcopy training courses should be viewed as an effective way to enhance the diagnostic ability of colposcopists, but implementing these courses in practice may not always be feasible to improve the overall diagnostic performance in a short period of time. Fortunately, AI has the potential to address colposcopic bottleneck, which could assist colposcopists in colposcopy imaging judgment, detection of underlying CINs, and guidance of biopsy sites. The automated workflow of colposcopy examination could create a novel cervical cancer screening model, reduce potentially false negatives and false positives, and improve the accuracy of colposcopy diagnosis and cervical biopsy. Conclusion We believe that a practical and accurate AI-guided digital colposcopy has the potential to strengthen the diagnostic ability in guiding cervical biopsy, thereby improves cervical cancer screening performance in LMICs and accelerates the process of global cervical cancer elimination eventually.

Background Female-specific cancers, particularly breast, cervical, ovarian, and uterine cancers, account for nearly 40% of all cancers in women. This study aimed to analyze the global epidemiological trends of these cancers from 1990 to 2021, offering insights into their evolving patterns and providing valuable information for health policymakers to allocate healthcare resources more effectively. Methods Data from the Global Burden of Disease Study 2021 (GBD 2021) were used to comprehensively assess the global incidence, mortality, and disability-adjusted life years (DALYs) of female-specific cancers. Age-standardized rates facilitated cross-regional comparisons, accounting for differences in population size and demographics. The socio-demographic index (SDI) was employed to categorize regions and evaluate correlations between cancer burden and economic level. In addition, risk factors attributable to female-specific cancer deaths and DALYs were assessed based on the comparative risk assessment model of the GBD project. Results From 1990 to 2021, the global burden of female-specific cancers increased at varying rates. In 2021, breast cancer accounted for 2.08 million incident cases, 0.66 million deaths, and 20.25 million DALYs globally. In comparison, cervical, ovarian, and uterine cancers had lower burdens, with 0.67 million, 0.30 million, and 0.47 million incident cases, respectively. Age-standardized rates of breast, ovarian, and uterine cancers showed positive correlations with SDI, while cervical cancer exhibited a negative correlation. Attributable risk factors for breast cancer-associated deaths in 2021 included dietary risks, high body-mass index (BMI), high fasting plasma glucose, alcohol use, tobacco use, and low physical activity. Additional risk factors were unsafe sex and tobacco use for cervical cancer, high BMI and occupational risks for ovarian cancer, and high BMI for uterine cancer. Conclusions The burden of female-specific cancers has increased in recent decades, with significant demographic and regional discrepancies. These findings highlight the urgent need for targeted public health interventions to mitigate the global impact of these cancers.

Cervical cancer is the leading cause of cancer deaths among Sub-Saharan African women. This systematic review aimed to identify information sources and their relation to cervical cancer knowledge, literacy, screening, and attitudes. Peer-reviewed literature was searched on 2 March 2022, and updated on 24 January 2023, in four databases—CINAHL Plus, Embase, PubMed, and Web of Science. Eligible studies included those that were empirical, published after 2002, included rural women, and reported on information sources and preferences. The quality of the selected articles was assessed using the Mixed Methods Appraisal Tool. Data extraction was conducted on an Excel spreadsheet, and a narrative synthesis was used to summarize findings from 33 studies. Healthcare workers were the most cited information sources, followed by mass media, social networks, print media, churches, community leaders, the Internet, and teachers. Community leaders were preferred, while healthcare workers were the most credible sources among rural women. There was generally low cervical cancer knowledge, literacy, and screening uptake, yet high prevalence of negative attitudes toward cervical cancer and its screening; these outcomes were worse in rural areas. A content analysis revealed a positive association of health information sources with cervical cancer literacy, knowledge, screening, and positive screening attitudes. Disparities in cervical cancer prevention exist between rural and urban Sub-Saharan African women.

Background Colposcopy diagnosis and directed biopsy are the key components in cervical cancer screening programs. However, their performance is limited by the requirement for experienced colposcopists. This study aimed to develop and validate a Colposcopic Artificial Intelligence Auxiliary Diagnostic System (CAIADS) for grading colposcopic impressions and guiding biopsies. Methods Anonymized digital records of 19,435 patients were obtained from six hospitals across China. These records included colposcopic images, clinical information, and pathological results (gold standard). The data were randomly assigned (7:1:2) to a training and a tuning set for developing CAIADS and to a validation set for evaluating performance. Results The agreement between CAIADS-graded colposcopic impressions and pathology findings was higher than that of colposcopies interpreted by colposcopists (82.2% versus 65.9%, kappa 0.750 versus 0.516, p  < 0.001). For detecting pathological high-grade squamous intraepithelial lesion or worse (HSIL+), CAIADS showed higher sensitivity than the use of colposcopies interpreted by colposcopists at either biopsy threshold (low-grade or worse 90.5%, 95% CI 88.9–91.4% versus 83.5%, 81.5–85.3%; high-grade or worse 71.9%, 69.5–74.2% versus 60.4%, 57.9–62.9%; all p  < 0.001), whereas the specificities were similar (low-grade or worse 51.8%, 49.8–53.8% versus 52.0%, 50.0–54.1%; high-grade or worse 93.9%, 92.9–94.9% versus 94.9%, 93.9–95.7%; all p  > 0.05). The CAIADS also demonstrated a superior ability in predicting biopsy sites, with a median mean-intersection-over-union (mIoU) of 0.758. Conclusions The CAIADS has potential in assisting beginners and for improving the diagnostic quality of colposcopy and biopsy in the detection of cervical precancer/cancer.

Laparoscopic/robotic radical hysterectomy has been historically considered oncologically equivalent to open radical hysterectomy for patients with early cervical cancer. However, a recent prospective randomized trial (Laparoscopic Approach to Cervical Cancer, LACC) has demonstrated significant inferiority of the minimally invasive approach. The aim of this study is to evaluate the oncologic outcomes of combined laparoscopic-vaginal radical hysterectomy. Between August 1994 and December 2018, patients with invasive cervical cancer were treated using minimally-invasive surgery at the Universities of Jena, Charité Berlin (Campus CCM and CBF) and Cologne and Asklepios Clinic Hamburg. 389 patients with inclusion criteria identical to the LACC trial were identified. In contrast to the laparoscopic/robotic technique used in the LACC trial, all patients in our cohort underwent a combined transvaginal-laparoscopic approach without the use of any uterine manipulator. A total of 1952 consecutive patients with cervical cancer were included in the analysis. Initial International Federation of Gynecology and Obstetrics (FIGO) stage was IA1 lymphovascular space invasion (LVSI+), IA2 and IB1/IIA1 in 32 (8%), 43 (11%), and 314 (81%) patients, respectively, and histology was squamous cell in 263 (68%), adenocarcinoma in 117 (30%), and adenosquamous in 9 (2%) patients. Lymphovascular invasion was confirmed in 106 (27%) patients. The median number of lymph nodes was 24 (range 2–86). Lymph nodes were tumor-free in 379 (97%) patients. Following radical hysterectomy, 71 (18%) patients underwent adjuvant chemoradiation or radiation. After a median follow-up of 99 (range 1–288) months, the 3-, 4.5-, and 10-year disease-free survival rates were 96.8%, 95.8%, and 93.1 %, and the 3-, 4.5-, and 10-year overall survival rates were 98.5%, 97.8%, and 95.8%, respectively. Recurrence location was loco-regional in 50% of cases with recurrence (n=10). Interestingly, 9/20 recurrences occurred more than 39 months after surgery. The combined laparoscopic-vaginal technique for radical hysterectomy with avoidance of spillage and manipulation of tumor cells provides excellent oncologic outcome for patients with early cervical cancer. Our retrospective data suggest that laparoscopic-vaginal surgery may be oncologically safe and should be validated in further randomized trials.

Background Cervical cancer screening participation remains insufficient in most countries. Our aim was to evaluate whether offering a HPV self-sampling kit, either mailed directly to the woman’s home or using timely opt-in procedures for ordering the kit, increased screening participation compared with a standard second reminder. Methods In this randomized, controlled effectiveness trial, 9791 Danish women aged 30–64 who were due to receive the second reminder were equally randomized to either: 1) direct mailing of a second reminder and a self-sampling kit (directly mailed group); 2) mailing of a second reminder that offered a self-sampling kit to be ordered by e-mail, text message, phone, or webpage (opt-in group); or 3) mailing of a second reminder to attend regular cytology screening (control group). In an intention-to-treat analysis, we estimated the participation rate at 180 days post intervention, by returning a self-sample or attending regular cytology screening. We calculated the proportion of women with a positive HPV self-sample who attended for cervical cytology triage at the general practitioner within 90 days. Results Participation was significantly higher in the directly mailed group (38.0%) and in the opt-in group (30.9%) than in the control group (25.2%) (participation difference (PD): 12.8%, 95% CI: 10.6–15.0% and PD: 5.7%, 95% CI: 3.5–7.9%, respectively). Within 90 days, 107 women (90.7%, 95% CI: 83.9–95.3%) with a HPV-positive self-sample attended follow-up. Conclusions Offering the opportunity of HPV self-sampling as an alternative to regular cytology screening increased participation; the direct mailing strategy was the most effective invitation strategy. A high compliance with follow-up was seen. Trial registration Current Controlled Trials NCT02680262 . Registered 10 February 2016.

Abstract Objective To assess CIN3+ risk in a Chinese cohort of outpatients undergoing contesting screening and to evaluate the portability of the American Society for Colposcopy and Cervical Pathology (ASCCP) risk-based management, which was primarily developed using data from the Kaiser Permanente of Northern California (KPNC) cohort. Methods Females aged 25-65 years who were screened with cytology and high-risk human papillomavirus (hrHPV) co-testing between 2011 and 2020 at Wuhan Union Hospital (WHUH) were retrospectively studied. The risks of immediate and 3-year CIN3+ were estimated via prevalence-incidence mixture models. Portability was evaluated via the ratio of the observation risk in the WHUH cohort to the expected risk in the KPNC cohort (O/E) and its 95% CI. Results A total of 96 318 females were included, and 16.83% of the women tested hrHPV-positive at initial screening, who had a CIN3+ immediate risk of 14.14%. The CIN3+ immediate risk varied between subgroups of positive HPV16 (34.09%), HPV18 (13.38%), other HPV types (6.71%), and negative hrHPV (0.12%). Compared to the KPNC cohort, our cohort exhibited a significantly higher CIN3+ immediate risk (1.42% vs 0.46%; O/E, 3.09; 95% CI, 2.92-3.26) and disproportionately increased cancer immediate risks in most subgroups requiring immediate colposcopy or treatment, as well as higher 3-year CIN3+ risks in women with hrHPV-negative ASC-US/NILM. Yet, the action threshold suggested by ASCCP, a CIN3+ immediate risk of 4%, showed good portability to our cohort. Conclusions Despite the higher risks in our cohort, the ASCCP clinical action threshold remains portable. For women with minimal abnormalities or normal results, shortened follow-up intervals should be considered.

Introduction Africa has one of the highest burdens of cervical cancer in the world. The unacceptably high incidence and mortality rates could be reduced through implementing a comprehensive approach to its prevention and control that includes screening, which however, is low in most low-and-middle-income countries. Hence, this systematic review aims at exploring factors that prevent women from utilising cervical cancer screening services in the region. Methods A mixed method systematic review was conducted. A search was performed on PubMed (Medline), EMBASE, CINAHL (EBSCOHOST) and Scopus databases for articles published until May 2019 without time, language or study design limits. Two reviewers critically appraised the included studies independently using the standard quality assessment criteria for evaluating primary research papers. Results of the quantitative and mixed methods studies were transformed into qualitative data and synthesised using thematic analysis. Results From a potential 2 365 studies, 24 from 11 countries met the eligibility criteria and were selected; eight qualitative, 13 quantitative, and three that used the mixed-method approach. The primary barriers were identified as poor access to screening services, lack of awareness and knowledge on cervical cancer and screening, and socio-cultural influences. Service providers perceived lack of skills, screening equipment and supplies, and staff shortages as the major barriers to the provision of screening services. Conclusion Barriers to cervical cancer screening in Africa are multifaceted and require a holistic approach that will address them concurrently at the health system, individual, interpersonal, community and structural levels. Political will complimented by stakeholder involvement is required in the development and implementation of strategies that will ensure acceptability, availability, accessibility, and affordability of screening to minimise barriers in accessing the service.

Background Primary cervical cancer screening and treating precancerous lesions are effective ways to prevent cervical cancer. However, the coverage rates of human papillomavirus (HPV) vaccines and routine screening are low in most developing countries and even some developed countries. This study aimed to explore the benefit of an artificial intelligence-assisted cytology (AI) system in a screening program for a cervical cancer high-risk population in China. Methods A total of 1231 liquid-based cytology (LBC) slides from women who underwent colposcopy at the Chinese PLA General Hospital from 2018 to 2020 were collected. All women had received a histological diagnosis based on the results of colposcopy and biopsy. The sensitivity (Se), specificity (Sp), positive predictive value (PPV), negative predictive value (NPV), false-positive rate (FPR), false-negative rate (FNR), overall accuracy (OA), positive likelihood ratio (PLR), negative likelihood ratio (NLR) and Youden index (YI) of the AI, LBC, HPV, LBC + HPV, AI + LBC, AI + HPV and HPV Seq LBC screening strategies at low-grade squamous intraepithelial lesion (LSIL) and high-grade squamous intraepithelial lesion (HSIL) thresholds were calculated to assess their effectiveness. Receiver operating characteristic (ROC) curve analysis was conducted to assess the diagnostic values of the different screening strategies. Results The Se and Sp of the primary AI-alone strategy at the LSIL and HSIL thresholds were superior to those of the LBC + HPV cotesting strategy. Among the screening strategies, the YIs of the AI strategy at the LSIL + threshold and HSIL + threshold were the highest. At the HSIL + threshold, the AI strategy achieved the best result, with an AUC value of 0.621 (95% CI, 0.587–0.654), whereas HPV testing achieved the worst result, with an AUC value of 0.521 (95% CI, 0.484–0.559). Similarly, at the LSIL + threshold, the LBC-based strategy achieved the best result, with an AUC of 0.637 (95% CI, 0.606–0.668), whereas HPV testing achieved the worst result, with an AUC of 0.524 (95% CI, 0.491–0.557). Moreover, the AUCs of the AI and LBC strategies at this threshold were similar (0.631 and 0.637, respectively). Conclusions These results confirmed that AI-only screening was the most authoritative method for diagnosing HSILs and LSILs, improving the accuracy of colposcopy diagnosis, and was more beneficial for patients than traditional LBC + HPV cotesting.