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• This review can better inform discussions with HR-HPV+ women and answer their questions about alternatives to surveillance. • This paper is the first of its kind to compile treatment options for women with HPV persistence and low-grade changes only. • Meta-analysis showed some therapies may lead to earlier HR-HPV resolution and CIN regression compared with natural clearance. In 2021, the World Health Organisation (WHO) updated its guidelines for cervical screening from cytology testing to primary high-risk human papillomavirus (HR-HPV) testing. This change in testing has effectively led to a 'new disease' as women are now aware of having a virus that induces changes that can cause cancer, which they would have been unaware of previously. While current management involves a 'watch and wait' approach and no active treatment, the anxiety associated with having HR-HPV may prompt some women to seek 'treatments' outside the screening programme. ● to identify potential treatment options available for women with persistent HR-HPV and/or low-grade cervical intraepithelial neoplasia (CIN), i.e. ≤CIN 1. ● to determine the clinical effectiveness of these treatments, namely by: ◦ HR-HPV clearance rate, and/or: ◦ CIN regression. We searched MEDLINE, PubMed, EMBASE, Web of Science and the Cochrane Library. We included cohort studies and randomised controlled trials (RCTs) only. Records (n = 2135) were screened in Rayyan by two independent reviewers. Quality assessment was conducted using the ROBINS-I tool and the ROB-2 tool. 12 studies (four cohort studies and eight RCTs) were included: six oral medications, two topical medications, one vaccination, and three non-surgical device treatments. Meta-analysis revealed that some therapeutic interventions, including vaginal gels, photodynamic therapy, and some oral medications, may lead to earlier resolution of persistent HR-HPV and regression of low-grade CIN when compared with natural clearance. This review can better inform discussions with HR-HPV+ women and answer their questions about alternatives to surveillance. [ABSTRACT FROM AUTHOR]

• Paiteling is effective and able to clear persistent high-risk human papillomavirus in a short period. • Single high-risk human papillomavirus infections have a higher clearance rate than mixed infections. • Paiteling has a higher clearance rate for low-grade squamous intraepithelial lesions than carbon dioxide laser. • Persistent high-risk human papillomavirus infection is prevalent in older adults. This study aims to evaluate the therapeutic outcomes of Paiteling and CO2 laser therapy on high-risk human papillomavirus. We retrospectively analyzed the data of 558 patients with HR-HPV low-grade squamous intraepithelial neoplasia (CIN1) from 2021 to 2023. Patients were selected and put into two groups: Paiteling and CO2 laser. Out of the 558 patients who were included in our final study, 239 (42.8 %) were treated with Paiteling, and 319 (57.2 %) were treated with CO2 laser vaporization. The mean age was 49.55 ± 12.10 years old. We observed that 27 (4.83 %) were younger than 30 years and 531 (95.1 %) were older than 30 years. We reviewed the patient's results at intervals of 3 months, 6 months, 12 months, and 24 months after each therapy. The results of the recurrence rate, effective viral clearance rate, and the effectiveness of both therapies on low-grade cervical lesions were determined using multivariate and univariate cox-regression analysis. The Kaplan-Meier curve was used to determine the HR-HPV conversion rate of each therapy. The median time for HR-HPV clearance was 6.00 months (95 % CI: 4.26–6.89) in the Paiteling group and 9.00 months (95 % CI: 15.92–22.67) in the CO2 laser group. There was a significant difference between the two groups (χ2 = 25.118, p-Value = 0.000). The HR-HPV clearance rate during 6–12 months for Paiteling and CO2 laser was 100 (55.6 %) and 80 (44.4 %), respectively. The clearance rate for both therapies from 6 to 18 months was statistically significant (6–12 months: p < 0.010, 12–18 months: p < 0.011). The Paiteling HR-HPV negative rate over 24 months 214 (89.5 %) is higher than CO2 laser 176 (55.2 %). Paiteling has a 5.4 % re-infection rate, which is marginally lower than the 5.6 % rate for CO2 lasers. The clearance rate for both therapies from 12 to 18 months [Paiteling: 20 (4.7 %) to 10 (3.6 %) and CO2 laser: 22 (8.4 %) to 15 (4.2 %)] was also significant (p < 0.011). The percentage of persistent Hr-HPV clearance rate for Paiteling patients was higher than carbon dioxide laser vaporization. No severe side effects were reported by the Paiteling patients compared to laser vaporization. This is due to the fact that Paiteling, as a traditional Chinese medicine, is a topical, non-invasive medicine, thus preserving the integrity of the cervix. Paiteling is an effective noninvasive therapy that can clear persistent HR-HPV associated with cervical low-grade squamous lesions in a relatively shorter period of time compared to CO2 laser ablation. [ABSTRACT FROM AUTHOR]

Purpose: Human papillomavirus (HPV) is the most common sexually transmitted infection, responsible for multiple HPV-related diseases, including almost all cervical cancers. The highly effective HPV vaccination has been recommended under the German HPV national immunization program (NIP) since 2007 and is reimbursed by health insurances. Vaccination uptake rates, however, remain suboptimal and data on the real-world impact of HPV vaccination in Germany are lacking. This study aims to demonstrate the population-level impact of Germany's NIP on HPV-related anogenital diseases among young women. Methods: Retrospective claims data analysis using a classic impact study design comparing disease prevalence among 28- to 33-year-old women before and after introduction of the HPV-immunization program in Germany. Claims data representing approximately two thirds of German health insurances were used. HPV-related disease outcomes included cervical cancer and high grade precancers (cervical intraepithelial neoplasia (CIN) 2+), anogenital warts, as well as vulvar, vaginal, and anal precancer/cancer. Results: Significant declines were seen for CIN2+, anogenital warts, and vaginal precancer/cancer. Prevalence of CIN2+ declined 51.1% from 0.92% (95% CI = 0.78%, 1.08%) to 0.45% (95% CI = 0.38%, 0.53%). There was a 38.6% decline in anogenital warts prevalence from 0.44% (95% CI = 0.36%, 0.54%) to 0.27% (95% CI = 0.22%, 0.32%) and 75.0% decline in vaginal precancer/cancer prevalence from 0.04% (95% CI = 0.02%, 0.07%) to 0.01% (95% CI = 0.00%, 0.02%). Conclusion: The German HPV-immunization program has led to significant declines in female anogenital disease among young women in Germany, highlighting the importance of the vaccination. Moreover, the data suggest that increasing vaccination coverage in Germany could further strengthen the public-health impact of its HPV-immunization program. [ABSTRACT FROM AUTHOR]

Objective: Over the past decade, liquid‐based cytology has replaced conventional cytology for cervical cancer screening in many countries, including Japan. We aimed to evaluate the efficacy of liquid‐based cytology using a large database and compare two major liquid‐based cytology platforms, SurePath and ThinPrep, to conventional cytology. Methods: Cervical cancer screening data were collected from the Japan Cancer Society between 2015 and 2019. The efficacy of liquid‐based and conventional cytology in detecting cervical intraepithelial neoplasia (CIN) was evaluated. Detection rates and positive predictive values were compared using a Poisson regression model. Results: We collected data of 3,918,149 participants, including 2,248,202 conventional cytology, 874,807 SurePath and 795,140 ThinPrep smears. The detection rate of CIN2 or more was 1.14 times higher using SurePath than that using conventional cytology (95% confidence interval [CI], 1.09–1.20; p < 0.001). Contrastingly, the detection rate of CIN2 or more was 0.91 times lower using ThinPrep (95% CI, 0.86–0.96; p < 0.001). The detection rates of CIN3 or more did not differ significantly between SurePath and conventional cytology (detection rate ratio, 1.04; 95% CI, 0.97–1.12; p = 0.224). The positive predictive value ratios of CIN2 or more were 0.80 using SurePath (95% CI, 0.76–0.84; p < 0.001) and 0.83 using ThinPrep (95% CI, 0.79–0.87; p < 0.001) compared with conventional cytology. Conclusions: Liquid‐based cytology, particularly SurePath, was useful for detecting CIN2 or higher in population‐based cervical cancer screening. Further widespread use of liquid‐based cytology methods would lead to efficient detection of cervical precancerous lesions. [ABSTRACT FROM AUTHOR]

Objective: We aimed to investigate differences between HPV‐16 mono‐ and HPV‐16/18 co‐infections in terms of cervical dysplasia and invasive cancer. Methods: This multicentre, retrospective study spanned from December 2017 to December 2020, involving women who visited gynaecological oncology clinics for colposcopy with either HPV‐16 or HPV‐16/18 positivity. A total of 736 patients, 670 in Group 1 (HPV‐16 positivity) and 66 in Group 2 (HPV‐16/18 positivity), were compared for the presence of CIN2+ lesions detected by colposcopic biopsy or endocervical curettage (ECC). Exclusions included hysterectomized patients, those with prior gynaecological cancers, and patients with HPV positivity other than types 16 and 18. Results: Among the included patients, 42.4% had a diagnosis of CIN2+ lesions. The cytology results demonstrated abnormal findings in 45.3% in Group 1 and 42.2% in Group 2, with no significant difference between the groups. ECC revealed CIN2+ lesion in 49 (8.7%) patients in group 1, while only 1 (1.7%) patient had CIN2+ lesion in group 2. There was no difference between 2 groups in terms of ECC result (p = 0.052). In group 1, 289 (43.1%) patients had CIN2+ lesion, while 23 (34.8%) patients had CIN2+ lesions in group 2. There was no difference between group 1 and 2 in terms of diagnosis of CIN2+ lesions (p = 0.19). Conclusion: This multicentre retrospective study found no significant differences between HPV‐16 mono‐ and HPV‐16/18 co‐infections regarding cervical pathologies. Larger studies are needed to validate and further explore these findings. [ABSTRACT FROM AUTHOR]

Cancer is a multifactorial disease characterized by the loss of control in the expression of genes known as cancer driver genes. Cancer driver genes trigger uncontrolled cell replication, which leads to the development of malignant tumors. A cluster of signal transduction pathways that contain cancer driver genes involved in cellular processes, such as cell proliferation, differentiation, apoptosis and dysregulated organ growth, are associated with cancer initiation and progression. In the present study, three signal transduction pathways involved in cervical cancer (CC) development were analyzed: The Hippo pathway (FAT atypical cadherin, yes-associated protein 1, SMAD4 and TEA domain family member 2), the Notch pathway [cellular-MYC, cAMP response element-binding binding protein (CREBBP), E1A-associated cellular p300 transcriptional co-activator protein and F-Box and WD repeat domain containing 7] and the nuclear factor erythroid 2-related factor 2 (NRF2) pathway [NRF2, kelch-like ECH-associated protein 1 (KEAP1), AKT and PIK3-catalytic subunit α]. Tumor samples from patients diagnosed with various stages of CC, including cervical intraepithelial neoplasia (CIN) 1, CIN 2, CIN 3, in situ CC and invasive CC, were analyzed. The mRNA expression levels were analyzed using reverse transcription-quantitative PCR assays, whereas protein expression levels were assessed through immunohistochemical tissue microarrays. High mRNA expression levels of c-MYC and AKT and low expression levels of NRF2 and KEAP1 were associated with a decreased survival time of patients with CC. Additionally, increased expression levels of c-MYC were detected in the invasive CC stage. At the protein level, increased NRF2 expression levels were observed in all five stages of CC samples compared with those in the cancer-free control samples. AKT1 was found to be dysregulated in the CIN 1 and CIN 2 stages, PI3K in the in situ and invasive stages, and CREBBP in the CIN 3 and in situ stages. In summary, the present study demonstrated significant changes in proteins of the Notch and NRF2 pathways in CC. NRF2 was overexpressed in all cervical cancer stages (cervical intraepithelial neoplasia, in situ CC and invasive CC). The present study makes an important contribution to the possible biomarker proteins to be analyzed for the presence of premalignant and malignant lesions in the cervix. [ABSTRACT FROM AUTHOR]

Introduction: Emerging evidence suggests that the vaginal microbiota is closely associated with cervical cancer. However, little is known about the relationships among the vaginal microbiota, vaginal metabolites, and cervical lesion progression in women undergoing cervical dysplasia. Methods: In this study, to understand vaginal microbiota signatures and vaginal metabolite changes in women with cervical lesions of different grades and cancer, individuals with normal or cervical dysplasia were recruited and divided into healthy controls (HC) group, low-grade squamous intraepithelial lesions (LSIL) group, high-grade squamous intraepithelial lesions (HSIL) group, and cervical cancer (CC) group. Vaginal secretion samples were collected for 16S rRNA gene sequencing, liquid chromatography coupled with mass spectrometry (LC-MS)-based metabolomics, and integrated analysis. Results: The results demonstrated that bacterial richness and diversity were greater in the CC group than the other three groups. Additionally, Lactobacillus was found to be negatively associated with bacterial diversity and bacterial metabolic functions, which increased with the degree of cervical lesions and cancer. Metabolomic analysis revealed that distinct metabolites were enriched in these metabolite pathways, including tryptophan metabolism, retinol metabolism, glutathione metabolism, alanine, aspartate, and glutamate metabolism, as well as citrate cycle (TCA cycle). Correlation analysis revealed positive associations between CC group-decreased Lactobacillus abundance and CC groupdecreased metabolites. Lactobacillus iners was both negative to nadB and kynU genes, the predicted abundance of which was significantly higher in the CC group. The linear regressionmodel showed that the combination of the vaginalmicrobiota and vaginal metabolites has good diagnostic performance for cervical cancer. Discussion: Our results indicated a clear difference in the vaginal microbiota and vaginal metabolites of women with cervical dysplasia. Specifically altered bacteria and metabolites were closely associated with the degree of cervical lesions and cancer, indicating the potential of the vaginal microbiota and vaginal metabolites as modifiable factors and therapeutic targets for preventing cervical cancer. [ABSTRACT FROM AUTHOR]

Objective: The research focused on a comparative analysis of triage strategies for women with Atypical Squamous Cells of Undetermined Significance (ASC-US) before and after receiving the HPV vaccine, aiming to optimize cervical cancer prevention strategies, especially in resource-limited healthcare settings. Materials and methods: Between September 2018 and December 2023, 7,511 women aged 21 years or older who underwent liquid-based cytology for cervical cancer screening were recruited. Women diagnosed with ASC-US were included in the study. All participants underwent HPV testing and liquid-based cytology examination, and those with abnormal results were referred for colposcopy. Women with abnormal colposcopy findings underwent further histopathological examination. The gold standard for diagnosis was pathological, with cervical intraepithelial neoplasia grade 2 or higher (CIN2+) on histology as the endpoints. In the final analysis, 933 women with ASC-US were enrolled as the unvaccinated group, with 179 of them testing positive for HPV 16/18. Assuming that all women would receive the bivalent vaccine targeting HPV 16/18 in the post-vaccine era, and given that the vaccine protection rate is 100% against HPV 16/18, then 754 women excluding those of HPV 16/18 positive would comprise the vaccinated group. Results: In the unvaccinated group, the overall HPV positivity rate was 59.27% among ASC-US women, with a 100% HPV prevalence rate among those with CIN2+ lesions. The combination genotyping model of HPV16/18 showed the highest specificity (81.77%) and the lowest referral rate (32.37%). In the vaccinated group, the HPV positivity rate was 49.61% among ASC-US women, with a 100% HPV prevalence rate among those with CIN2+ lesions. The specificity of HPV33/58 was the highest (86.99%), and the colposcopy referral rate was lowest (27.54%), with statistical significance. Sensitivity, positive predictive value, and negative predictive value were not statistically significant. Conclusion: HPV16/18 demonstrated a more efficacious triaging effect in the unvaccinated group. HPV33/58 will potentially replace HPV16/18 as the priority screening genotyping among vaccinated populations. [ABSTRACT FROM AUTHOR]

Transitioning to an individualized risk-based approach can significantly enhance cervical cancer screening programs. We aimed to derive and internally validate a prediction model for assessing the risk of cervical intraepithelial neoplasia grade 3 or higher (CIN3+) and cancer in women eligible for screening. This retrospective study utilized data from the Estonian electronic health records, including 517,884 women from the health insurance database and linked health registries. We employed Cox proportional hazard regression, incorporating reproductive and medical history variables (14 covariates), and utilized the least absolute shrinkage and selection operator (LASSO) for variable selection. A 10-fold cross-validation for internal validation of the model was used. The main outcomes were the performance of discrimination and calibration. Over the 8-year follow-up, we identified 1326 women with cervical cancer and 5929 with CIN3+, with absolute risks of 0.3% and 1.1%, respectively. The prediction model for CIN3 + and cervical cancer had good discriminative power and was well calibrated Harrell's C of 0.74 (0.73–0.74) (calibration slope 1.00 (0.97–1.02) and 0.67 (0.66–0.69) (calibration slope 0.92 (0.84–1.00) respectively. A developed model based on nationwide electronic health data showed potential utility for risk stratification to supplement screening efforts. This work was supported through grants number PRG2218 from the Estonian Research Council, and EMP416 from the EEA (European Economic Area) and Norway Grants. [ABSTRACT FROM AUTHOR]

This post hoc analysis explored the age-specific risk of cervical precancer in women infected with human papillomavirus (HPV), using data from a cohort of 7263 participants aged 21-71years undergoing cervical screening. We found a slightly varied prevalence of high-risk HPV (hrHPV) in different age, with highest in women under 30 years old (9.28% for 13 hrHPVs tested by HC2-HPV, 10.82% for 14 hrHPVs tested by DH3-HPV). However, the prevalence of cytology abnormalities peaked in age 30–39 years (~ 3.6%). A total of 5840 women completed 3-year follow-up. Among them, 558 were positive for HC2 assay and 583 were positive for DH3-HPV at baseline. Of note, the 3-year cumulative risks for cervical intraepithelial neoplasia grade 2+ (CIN2+) or grade 3+ (CIN3+) in women infected with high-risk HPV did not increase with age but declined (e.g., 41.67%, 27.78%, 26.42%, 15.98%, and 18% for CIN2 + risk in HC2-positive women at year 25–29, year 30–39, year 40–49, year 50–59, and year 60–71, respectively). If stratified by the median age, younger women (25–48 years) positive with HC2-HPV at baseline had a higher 3-year CIN2+/CIN3 + risk than older women (49–71 years) [26.55% (95%CI = 21.8-31.92%) vs. 18.28% (95%CI = 14.11-23.34%), P = 0.019; 15.52% (95%CI = 11.81-20.14%) vs. 9.7% (95%CI = 6.71-13.83%), P = 0.039]. Similarly, for women positive with DH3-HPV at baseline, younger group had a higher 3-year CIN2+/CIN3 + risk than older group [26.44% (95%CI = 21.73-31.75%) vs. 17.01% (95%CI = 13.11-21.78%), P = 0.006; 15.25% (95%CI = 11.6-19.8%) vs. 9.03% (95%CI = 6.24-12.9%), P = 0.021]. These findings indicate the potential value of age-specific risk assessment in cervical cancer screening. [ABSTRACT FROM AUTHOR]

Introduction: To establish clinical trial readiness for dystonia, a crucial step is to develop a Patient-Centered Outcome (PCO) measure to capture therapeutic response in focal dystonia such as in cervical dystonia (CD). Botulinum neurotoxin (BoNT) is the gold standard treatment for focal dystonia and yields improvement; yet the therapy may not meet all patient expectations as there is a high rate of discontinuation. A PCO that can measure therapeutic response, including the waxing and waning benefit of BoNT, across multiple domains and is easy to use on a frequent basis in the home environment is critical. Methods: A modified iterative Delphi process based on FDA (Food and Drug Administration) guidelines was used to develop and select items to document patient symptoms and response to treatment. Potential items then were improved using patient focus groups, validated for content with specialist panels, and confirmed items based on a patient survey. Using data from 200 CD patients in the Dystonia Coalition Natural History Database, initial PCO items were identified. Utilizing Random Forests, prospective items were analyzed for their contribution to the overall severity scores on the clinical and patient-centered outcome scales. Items that were repetitive were merged. Iterative meetings with a specialist panel consisting of neurologists, physical therapists, and Patient Advocacy Group (PAG) representatives as well as virtual focus groups of CD patients were held. An online survey was conducted with over 600 CD patients participating. Finally, specialist panel members provided input for a content validity ratio (CVR) with iterations until there was good agreement as to the relevance and clarity of the items. Results: PCO measures tailored for CD were successfully developed. The PCO consists of 16 items covering three domains (motor, disability, and psychosocial) and reflects the input of international specialist panels, more than 800 CD patients, and PAGs (patient advocacy groups) following FDA guidance. The PCO is simple enough to be used in an app-based format compatible with smartphones and tablets. Conclusion: This comprehensive CD PCO measure was developed through the combination of using robust existing patient centered data (from previous Dystonia Coalition Projects); active engagement with PAGs to provide the patient voice; and use of virtual focus groups and online surveys. This PCO will be used in a prospective study to characterize the therapeutic response to BoNT over time. This will provide peak effect size as well as capturing the "yoyo" effect during BoNT treatment; and will prepare for a future trials. [ABSTRACT FROM AUTHOR]

Cervical intraepithelial neoplasia (CIN) is a collective term for specific precancerous lesions associated with cervical cancer (CC). Given the current poor prognosis, it is imperative to diagnose CIN at an early stage and identify the markers linked to its pathogenesis and prognosis, despite the disease's documented slow course and numerous levels of cellular alterations. We explored the expression level of the new marker apolipoprotein B mRNA-editing enzyme-catalytic polypeptide-like 3G (APOBEC3G, A3G) and its regulatory effect on CIN. Cell proliferation were assessed using Cell Counting Kit-8 (CCK-8) and 5-ethynyl-2'-deoxyuridine (EdU) staining. Apoptosis rate was detected by flow cytometry. We used immunofluorescence to determine light chain 3B (LC3B) expression. Western blotting was used to detect Bcl2-Associated X (Bax), B-cell lymphoma 2 (Bcl-2), Cleaved caspase-3, p62, LC3-II/LC3-I, transforming growth factor-beta (TGF-β) and decapentaplegic homolog 2 (Smad2) expressions. A3G knockdown significantly inhibited cervical intraepithelial neoplasia cell proliferation, significantly increasing the apoptosis rate and the Bax/Bcl-2 ratio. Also, Cleavedcaspase- 3 and LC-II expressions were significantly increased, and p62 expression was decreased. The TGF-β/Smad2 signaling pathway was significantly inhibited. In cervical intraepithelial neoplasia, APOBEC3G inhibits apoptosis and autophagy of W12 cells through TGFβ/Smad2 signaling pathway. In conclusion, we determined that APOBEC3G has a regulatory effect on CIN, which opens a new way to explore its pathogenesis and improve the accuracy of prognosis. [ABSTRACT FROM AUTHOR]

Persistent infection with human papillomavirus (HPV) is a key driver in the development of cervical cancer (CC). We aimed to elucidate the relationship between preoperative high-risk HPV status and prognosis of cervical intraepithelial neoplasia (CIN) in patients undergoing cervical conization. We retrospectively analyzed data from 2546 patients with CIN who underwent HPV deoxyribonucleic acid (DNA) testing and cervical conization in two individual years, i.e., 2009 and 2013, at 205 Japanese institutions. Patients were categorized into five groups based on their high-risk HPV status: highrisk HPV negative (Group 1); HPV 16/18 positive (Group 2); positive for HPV types 31, 33, 35, 45, 52 or 58 (Group 3); other high-risk HPV positive (Group 4); and unconfirmed high-risk HPV status (Group 5). Logistic and Cox regression analyses were conducted for statistical assessment. The distribution of participants across Groups 1 to 5 was 8.1%, 26.3%, 20.1%, 3.0% and 42.5%, respectively. Cervical conization identified CC in 3.9% (99 patients) of the cohort. Multivariate analysis revealed that diagnostic conization, preoperative diagnosis of CIN grade 3 and HPV 16/18 positivity were significant risk factors for post-conization CC. Notably, no correlation was found between preoperative HPV status and post-conization recurrence in patients without CC. HPV types 16 and 18 emerged as significant independent risk factors for CC development following conization. The study findings underscore the need for vigilant management of this patient group. However, the presence of high-risk HPV before conization was not correlated with the risk of recurrence. [ABSTRACT FROM AUTHOR]

Perinatal care provides important health care opportunities for many individuals at risk for cervical cancer. Pregnancy does not alter cervical cancer screening regimens. ASCCP risk-based management has a colposcopy threshold of a 4% immediate risk of cervical intraepithelial neoplasia (CIN) 3 or cancer, but the actual risk can be considerably higher based on current and past screening results. Improving cervical cancer outcomes with diagnosis during pregnancy rather than postpartum and facilitating further evaluation and treatment postpartum for lesser lesions are the perinatal management goals. Although colposcopy indications are unchanged in pregnancy, some individuals with lower risk of CIN 2-3 and reliable access to postpartum evaluation may defer colposcopy until after delivery. Cervical intraepithelial neoplasia diagnosed in pregnancy tends to be stable, with frequent regression postpartum, though this is not universal. Colposcopic inspection during pregnancy can be challenging. Although biopsies in pregnancy are subjectively associated with increased bleeding, they do not increase complications. Endocervical curettage and expedited treatment are unacceptable. Treatment of CIN 2-3 in pregnancy is not recommended. Excisional biopsies in pregnancy are reserved for suspicion of malignancy that cannot be confirmed by colposcopic biopsy and when excisional biopsy results would alter oncologic or pregnancy care. Surveillance of high-grade lesions in pregnancy uses human papillomavirus-based testing, cytology, and colposcopy, with biopsy of worsening lesions every 12-24 weeks from diagnosis until postpartum evaluation. Mode of delivery does not definitively affect persistence of CIN postpartum. Postpartum care may involve a full colposcopic evaluation or expedited excisional procedure if indicated. [ABSTRACT FROM AUTHOR]

Background: Computer‐assisted screening (CAS) shows equal performance compared to manual screening, although results are heterogeneous. Furthermore, using CAS may save costs through a potentially increased screening productivity of technicians, therefore also offering a solution for temporary and structural capacity shortage. We evaluated the circumstances under which CAS will be cost‐effective compared to manual cytology triage in a primary HPV‐based cervical screening programme. Methods: Microsimulation model MISCAN‐Cervix was used to evaluate 198 different CAS scenarios with varying probabilities to detect cervical intraepithelial neoplasia grade 1 (CIN1) and CIN3 and cost reductions per test, compared to manual cytology triage. Cost‐effectiveness was evaluated by costs per (quality‐adjusted) life year ((QA)LY) gained. Results: CAS will be cost‐effective in all scenarios, except for the following combinations: (1) no cost reduction and an increased probability of detecting CIN1, (2) a cost reduction of €2 per test and an increased probability of detecting CIN1 from 4% onwards or (3) a cost reduction of €4 per test and an increased probability of detecting CIN1 from 6% onwards, compared to manual cytology triage. All CAS scenarios with any reduction in the probability of detecting CIN1 (i.e., increased CIN2+ specificity), or a reduction in costs from €6 per test onwards suggested a more cost‐effective strategy compared to manual cytology triage. Conclusion: As we based our analysis on a realistic range in costs and test performance, the implementation of CAS is likely to be cost‐effective. Our results can be used as a guideline to advise when to choose CAS instead of manual cytology triage. Computer‐assisted screening (CAS) is an evident substitute for manual cytology screening as a triage test in a primary HPV‐based setting. This is the first study investigating under which circumstances CAS is cost‐effective in a primary HPV‐based screening programme. We showed that in case of increased CIN2+ specificity and cost reduction from €6 per test, CAS was more cost‐effective than manual cytology triage. So, implementing CAS is likely to be cost‐effective in primary HPV‐based screening, which can guide decision‐making. [ABSTRACT FROM AUTHOR]

Objective: This study aims to analyse high‐grade intraepithelial lesions (LIEHG) observed in a screening programme from 2010 to 2018 to more accurately describe them and formulate recommendations for best practices in the context of screening evolution following the introduction of an HPV test in primary cervical cancer screening in 2020. Methods: This study included 305,940 asymptomatic women aged 25–65 years. The eligible population was invited to undergo a screening cervico‐uterine‐smear every 3 years. If this smear was normal, the woman received a new invitation. In the case of a positive screen, the patient underwent further diagnostic procedures, such as colposcopy and biopsy to confirm the diagnosis. Only those diagnosed with LIEHG and above proceeded to treatment. The diagnoses associated with LIEHG were those related to the WHO Classification of tumours of the uterine cervix. Results: Positive smears led to the diagnosis of 3230 LIEHG. The prevalence of LIEHG in the screened population was 0.4%. The LIEHG distribution varied significantly according to the age of the women. The probability of diagnosing LIEHG in young women was 12.2% at 25–29 years. This probability decreased by half after 50 years. We observed that the type of smear was significantly associated with LIEHG detection. The positive predictive value for diagnosing LIEHG was 70.3% for high‐grade squamous intraepithelial lesion (HSIL) smears and 35.1% for atypical squamous cells cannot exclude HSIL (ASC‐H) smears. Conclusion: In the study population, the prevalence of LIEHG was high in women under 35 years. Low‐grade smears were correlated with the risk of LIEHG and should prompt screening facilities to allocate resources to ensure active follow‐up of LSIL and ASC‐US smears. Adherence to cytological screening recommendations was associated with a reduced risk of LIEHG in multivariate analysis. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the sensitivity of human papillomavirus (HPV) tested urine to detect high‐grade cervical precancer (cervical intraepithelial neoplasia grade 2+ [CIN2+]) using two urine collection devices. Design: Randomised controlled trial. Setting: St Mary's Hospital, Manchester, UK. Population: Colposcopy attendees with abnormal cervical screening; a total of 480 participants were randomised. Matched urine and cervical samples were available for 235 and 230 participants using a first‐void urine (FVU)‐collection device and standard pot, respectively. Methods: Urine was self‐collected and mixed with preservative – randomised 1:1 to FVU‐collection device (Novosanis Colli‐pee® 10 mL with urine conservation medium [UCM]) or standard pot. Matched clinician‐collected cervical samples were taken before colposcopy. HPV testing used Roche cobas® 8800. A questionnaire evaluated urine self‐sampling acceptability. Main outcome measures: The primary outcome measured sensitivity of HPV‐tested urine (FVU‐collection device and standard pot) for CIN2+ detection. Secondary outcomes compared HPV‐tested cervical and urine samples for CIN2+ and evaluated the acceptability of urine self‐sampling. Results: Urine HPV test sensitivity for CIN2+ was higher with the FVU‐collection device (90.3%, 95% CI 83.7%–94.9%, 112/124) than the standard pot (73.4%, 95% CI 64.7%–80.9%, 91/124, p = 0.0005). The relative sensitivity of FVU‐device‐collected urine was 0.92 (95% CI 0.87–0.97, pMcN = 0.004) compared with cervical, considering that all women were referred after a positive cervical HPV test. Urine‐based sampling was acceptable to colposcopy attendees. Conclusions: Testing of FVU‐device‐collected urine for HPV was superior to standard‐pot‐collected urine in colposcopy attendees and has promising sensitivity for CIN2+ detection. General population HPV testing of FVU‐device‐collected urine will establish its clinical performance and acceptability as an alternative to routine cervical screening. [ABSTRACT FROM AUTHOR]

Simple Summary: We studied how different types of high-risk human papillomavirus (HR-HPV) are distributed in early and advanced precancerous cervical lesions to better understand cervical cancer risks. A total of 559 cases were analyzed with results from a diagnostic test for HR-HPV and a special immunostaining method (DS) that helps identify cervical precancer potential that could enhance the effectiveness of the secondary cervical cancer prevention The investigation included a corresponding histology result from a colposcopic biopsy. The study found significant differences in the presence of HPV 16 and positive staining results between advanced lesions and those that were either negative or less severe. However, no significant difference was found between negative and less severe lesions. This study highlights the importance of understanding HPV type distribution and the use of dual staining in detecting and assessing the risk of cervical precancers. Background: Determining the distribution of high-risk human papillomavirus (HR-HPV) types in histologic low-(LSIL) and high-grade (HSIL/CIN2+) squamous intraepithelial lesions through a diagnostic process in a cervical cancer prevention provides one of the key etiological factors behind further progression and persistence. Incorporating novel high-grade cervical lesion biomarkers such as p16/Ki67 dual staining (DS) alongside HPV typing has become important in detecting cervical precancers. Methods: Among 28,525 screening tests and 602 histology results, 559 cases with HR-HPV and histology results obtained from colposcopic biopsy were retrospectively analyzed, together with DS status. The χ2 test with Bonferroni correction evaluated the differences in HR-HPV type prevalence and DS positivity across three histologic study groups. Results: A statistically significant difference in the prevalence of HPV 16 was observed between negative and HSIL/CIN2+ (p = 0.00027) groups, as well as between the LSIL/CIN1 and HSIL/CIN2+ groups (p = 0.00041). However, no significant difference was found between the negative and LSIL/CIN1 groups. Similarly, the DS positivity difference was significant between the negative and HSIL/CIN2+ (p < 0.0001) and between the LSIL/CIN1 and HSIL/CIN2+ groups (p < 0.0001), but there was no significant difference between the negative and LSIL/CIN1 groups. Conclusions: The study highlights the heterogeneous nature of HPV-related cervical pathologies, and the distinct risks associated with different cervical lesion grades, emphasizing the importance of HR-HPV type distribution and DS status. [ABSTRACT FROM AUTHOR]

This study aimed to describe the prevalence of high‐risk human papillomavirus (HR‐HPV) types in the anal canal in a cohort of people living with HIV (PLWHIV) with a history of malignancy. Setting: Referral tertiary care hospital for adult patients with cancer. Methods: We reviewed data of patients from the AIDS Cancer Clinic on antiretroviral therapy in chronic control who were consecutively referred for high‐resolution anoscopy (HRA), where they underwent anal evaluation, collection of specimens for anal cytology and anal human papillomavirus (HPV) followed by HRA with directed biopsy if needed. Results: A total of 155 patients were included; 149 (96.1%) were men, all of them men who have sex with men (MSM); the median age was 39 (IQR 32‐47) years; 105 (67.7%) with Kaposi sarcoma, 40 (25.8%) with non‐Hodgkin lymphoma and 10 (6.4%) with other neoplasms; only 7 (4.5%) had active cancer. The prevalence of HR‐HPV infection was 89% (n=138) (95% CI 83–93) with at least one HR‐HPV infection, and 62% (96) had coinfection with at least two types; the median HR‐HPV types of coinfection were 3 (IQR 2–4). The number of patients infected with HPV 16 was 64 (41.3%, 95% CI 33.8–49.3), HPV 18 was 74 (47.7%, 95% CI 39.9–55.7) and with both 35 (22.6%). Some 59 patients (38%) had high‐grade squamous intraepithelial lesions (HSIL) and 49 (31.6%) had low‐grade squamous intraepithelial lesions (LSIL). The prevalence of HR‐HPV and HSIL among patients aged ≤35 and >35 years was the same. Conclusions: In this cohort of PLWHIV with a history of malignancy we found a high prevalence of HR‐HPV 16 and 18 and anal HSIL, even in persons aged ≤35 years. These data highlight the importance of anal cancer screening in PLWHIV and history of malignancy. [ABSTRACT FROM AUTHOR]

Aim: The importance of human papillomavirus (HPV) co‐testing using physician‐, self‐, and urine‐collected samples to predict cervical intraepithelial neoplasia (CIN) grade 1–2 prognoses has not been previously reported. Therefore, this study aimed to investigate outcomes of patients with CIN 1–2 who simultaneously underwent physician‐, self‐, and urine‐collection sampling tests. Methods: This study was conducted in Japan between October 2019 and November 2022 and examined the proportion of cases with CIN 1–2 progressions, the percentage of cases with persistent CIN 1–2, and the outcome differences according to the results of physician‐, self‐, and urine‐sampling tests. Results: There were 105 and 59 CIN 1 and 2 cases, respectively, with progression or persistence in 27 (29.3%) and 21 (50.0%) cases, respectively. The median follow‐up was 20 and 12 months, respectively. Progression and persistence of CIN 1 were significantly associated with HPV‐positive physician‐ and self‐collected samples. No significant difference was observed between cases with CIN 2 who had HPV‐positive and HPV‐negative results using any sampling method. Conclusions: Physician‐ and self‐testing for HPV are crucial for predicting disease progression risk in CIN 1 cases. Future research with an extended observation period and consideration of the progression risks is warranted. [ABSTRACT FROM AUTHOR]

Cervical cancer (CC) results from a subsequent process, starting from the infection of normal cervical epithelium with oncogenic human papillomavirus and gradually progressing to cervical intraepithelial neoplasia (CIN), before finally developing into invasive cervical cancer (ICC). Over recent decades, dietary micronutrients have gained much attention due to their pivotal role in cancer prevention. We reviewed several relevant literature studies to investigate the protective roles of dietary nutrient intake in CC. Dietary intake of vitamin C, green-yellow vegetables, and provitamin A carotenoids that are rich sources of antioxidants may widely inhibit the process of CC development, whereas vitamins A and D might be more helpful in preventing the early events in the disease development. Vitamin E, lycopene, and folate are more effective for the treatment of high-grade CIN. Fruits exert their protective effects in the late stages of the cancer process, thus playing a vital role in ICC prevention. Polyphenols, flavonoids, and polyunsaturated fatty acids are more often used in cases of CC in combination with chemotherapy and radiotherapy. Thus, as a primary prevention strategy, the health benefits of various nutrients in CC must be clarified by vitro and in vivo approaches rather than epidemiological studies. [ABSTRACT FROM AUTHOR]

• In Reunion Island, incidence and mortality of cervical cancer are high. • HPV vaccination coverage is low. • HPV genotypes contained in the nonavalent vaccine are more frequent. • Infection with HPV genotypes contained in the vaccine lead to more severe cervical dyplasia. The primary objective of this study was to assess the prevalence and genotypes of human papilloma virus (HPV) in Reunion Island. Study design. In this retrospective study, data were collected from the database of microbiology and anatomopathology laboratories from August 1st 2020 to July 31st 2021. The overall prevalence of human papillomavirus (HPV) in Reunion Island was 14.5 %. The most common HPV genotypes in Reunion Island, were as follows: cluster of HPV 56 + 59 + 66, representing 3.3 % of all samples, cluster of HPV 35 + 39 + 68 (3.2 %), HPV 16 (2.9 %), HPV 33 + 58 (2.3 %) and HPV 52 (2.2 %). HPV types contained in the vaccine accounted for 59.3 % of HPV-positive samples and significantly resulted in more severe cytological lesions compared to HPV types that were not included in the vaccine (p < 0.01). Cervical dysplasia were identified in 57.3 % of HPV-positive cases. Multiple infections were detected in 23.2 % of the cases and were more frequent among younger women (<30 years) and in pathological smears (p < 0.001). In this study, we highlighted that HPV genotypes contained in the vaccine are the most represented in Réunion Island and are the most likely to generate significant cytological abnormalities. Therefore, continuous efforts are necessary to increase HPV vaccination coverage, which is currently in the island among the lowest in developed countries, despite the high mortality rate associated with cervical cancer. Furthermore, considering the inequal offensive capacity of each HPV, identifying patients' HPV infection subtype, could allow customized management and follow-up. [ABSTRACT FROM AUTHOR]

Purpose: Cervical cancer is the fourth most common cancer in women worldwide. A successful screening concept for cervical cancer reduces the incidence and mortality of cervical cancer. Quality indicators (QIs) derived from the screening guidelines for cervical cancer and used by the certified dysplasia units and dysplasia consultancies are evaluated in this paper. The aim of this paper is to present the current data from the annual reports of these units and consultancies. Methods: The results of the basic data and indicators for the audit year 2022 in the gynaecological dysplasia consultancies and units are presented. In 2022, 84 dysplasia consultancies and 42 units were audited. 40 units and 84 consultancies are included in the annual report. QI outcomes for patients treated in certified dysplasia units and dysplasia consultancies are analysed. Median, overall proportion, and standard deviation were calculated for each QI. Results: The indicator year 2021 was analysed, which was audited in 2022 and evaluated in 2023. A total of nine QIs were analysed. Most target goals were met by the 84 certified dysplasia consultancies and by the 40 dysplasia units. The QIs evaluated are implemented to a very high degree. The targets for the three QIs were achieved by both the dysplasia consultancies and the units in at least 95% of the certified centres (QI 1: 100%, QI 2: 95%, QI 3: 100%; QI 1: 100%, QI 2: 97%, QI 3: 100%, respectively). The presentation of patients to the tumour board by the consultancies/units is working; the units are attending the tumour board more regularly than in previous years. Where the target was not met, the auditors issued deviations or reduced the duration of the certificate. The cases are discussed intensively in the sense of an individual case analysis and with the determination of measures on-site. Conclusions: The targets for the various indicators were largely met by the dysplasia consultancies and units in the 2022 audit year. The certification of gynaecological dysplasia consultancies/units which have to cooperate with certified gynaecological cancer centres, has for the first time ensured the continuity of healthcare from prevention and early diagnosis to treatment of gynaecological cancers. [ABSTRACT FROM AUTHOR]

Purpose: This study aims to investigate the psychological distress experienced by patients with an initial diagnosis of abnormal Pap smears or dysplastic changes of the cervix uteri. It investigated whether patients' age, education, information level and approach to information acquisition have an impact on their psychological distress. Methods: A total of 364 female patients, aged 20–80 years, referred to the special dysplasia consultation hour at the Department of Obstetrics and Gynecology, Wuerzburg, completed a questionnaire containing validated items to assess information level, information acquisition, information needs and psychological distress, including a distress thermometer. Data from questionnaires and medical reports were used for analysis. Results: The study found that 56.9% of patients experienced psychological distress before their first visit. Patients under 44 years of age, especially those with concerns about fertility and sexuality, and those with lower levels of education showed higher levels of distress (p-value = 0.018 and p-value = 0.037). 40.9% of patients felt poorly informed and 53.7% of patients wanted more information before their visit. Correlational analysis showed that the method of obtaining information correlated with the desire for more information (p-value < 0.001). Those who received information via the Internet felt less informed, wanted more information and experienced more anxiety. Conclusion: These findings highlight the need for improved patient education strategies and effective doctor-patient communication to address the knowledge gap and reduce patient distress. In addition, healthcare providers should ensure that patients have access to reliable online resources for accurate information. [ABSTRACT FROM AUTHOR]

Background: Minimally-invasive 5-aminolevulinic acid photodynamic therapy (ALA-PDT) is used for treating cervical high-grade squamous intraepithelial lesions (HSIL/CIN2). The purpose of this study was to analyze the factors affecting the efficacy of ALA-PDT in the treatment of cervical HSIL/CIN2 in order to guide physicians in making appropriate treatment decisions. Methods: A retrospective study including 69 female patients with pathologically diagnosed HSIL/CIN2 was conducted. Patients were given six doses of 20% ALA-PDT at 7–14-day intervals. Cytology, HPV testing, colposcopy, and pathology were performed before treatment and at 6-month follow-up after treatment to assess efficacy. The main outcome of this study was the regression of HSIL/CIN2 and the clearance of high-risk HPV (hrHPV) infection after ALA-PDT treatment. Clinicopathological characteristics were collected to analyze the factors affecting the effectiveness of ALA-PDT treatment for HSIL/CIN2. Results: Between the successful and failed lesion regression group, there was a significant difference in sleeping disorders (p < 0.05). Between the successful and failed hrHPV clearance group, no statistically significant factors were found. With sensitivity values of 0.556 and 0.778, respectively, multivariate analysis showed that current smoking and sleeping disorders were independent prognostics of failure in lesion regression after ALA-PDT treatment. Conclusions: Smoking and sleep disorders were independent risk factors for failure in HSIL/CIN2 regression following ALA-PDT, suggesting the need for careful consideration of ALA-PDT for patients with these conditions. [ABSTRACT FROM AUTHOR]

In this comprehensive review supported by clinical examples, the authors explore the topic of cervical cancer in pregnancy, with emphasis on potential pre-cancer progression, the possibility of coexisting preinvasive and invasive disease, and neoadjuvant chemotherapy. This manuscript addresses the challenges of managing cervical cancer in pregnant women with a pregnancy-preserving approach, including the importance of screening, the timing of surgery, and the impact of pregnancy on the course of the disease. The first case study illustrates the potential for a benign cervical lesion to transform into a malignant one during pregnancy and the possible coexistence of preinvasive lesions together with early-stage cervical cancer. It also questions the rationale behind the non-treatment of pregnant patients initially diagnosed with CIN 2/3 during pregnancy. The second presented clinical example shows the histologically confirmed response to neoadjuvant chemotherapy, resulting in a radiologically diagnosed FIGO stage IIA1 being downgraded to adenocarcinoma in situ in the histology report after surgery performed six weeks postpartum. The treatment of cervical cancer, which is becoming increasingly prevalent among pregnant women, and the necessity for an individualized diagnostic and therapeutic approach represent significant challenges for contemporary medicine. Discrepancies in therapeutic options proposed among centers within the same region lead to the conclusion that there is a need for centralization and unification of evidence-based management in referral centers with both high-level oncological and perinatal care. [ABSTRACT FROM AUTHOR]

The concordance rate between conization and colposcopy‐directed biopsy (CDB) proven cervical high‐grade squamous intraepithelial lesion (HSIL) were 64−85%. We aimed to identify the risk factors associated with pathological upgrading or downgrading after conization in patients with cervical HSIL and to provide risk‐stratified management based on a machine learning predictive model. This retrospective study included patients who visited the Obstetrics and Gynecology Hospital of Fudan University from January 1 to December 31, 2019, were diagnosed with cervical HSIL by CDB, and subsequently underwent conization. A wide variety of data were collected from the medical records, including demographic data, laboratory findings, colposcopy descriptions, and pathological results. The patients were categorized into three groups according to their postconization pathological results: low‐grade squamous intraepithelial lesion (LSIL) or below (downgrading group), HSIL (HSIL group), and cervical cancer (upgrading group). Univariate and multivariate analyses were performed to identify the independent risk factors for pathological changes in patients with cervical HSIL. Machine learning prediction models were established, evaluated, and subsequently verified using external testing data. In total, 1585 patients were included, of whom 65 (4.1%) were upgraded to cervical cancer after conization, 1147 (72.4%) remained having HSIL, and 373 (23.5%) were downgraded to LSIL or below. Multivariate analysis showed a 2% decrease in the incidence of pathological downgrade for each additional year of age and a 1% increase in lesion size. Patients with cytology > LSIL (odds ratio [OR] = 0.33; 95% confidence interval [CI], 0.21–0.52), human papillomavirus (HPV) infection (OR = 0.33; 95% CI, 0.14–0.81), HPV 33 infection (OR = 0.37; 95% CI, 0.18–0.78), coarse punctate vessels on colposcopy examination (OR = 0.14; 95% CI, 0.06–0.32), HSIL lesions in the endocervical canal (OR = 0.48; 95% CI, 0.30–0.76), and HSIL impression (OR = 0.02; 95% CI, 0.01–0.03) were less likely to experience pathological downgrading after conization than their counterparts. The independent risk factors for pathological upgrading to cervical cancer after conization included the following: age (OR = 1.08; 95% CI, 1.04–1.12), HPV 16 infection (OR = 4.07; 95% CI, 1.70–9.78), the presence of coarse punctate vessels during colposcopy examination (OR = 2.21; 95% CI, 1.08–4.50), atypical vessels (OR = 6.87; 95% CI, 2.81–16.83), and HSIL lesions in the endocervical canal (OR = 2.91; 95% CI, 1.46–5.77). Among the six machine learning prediction models, the back propagation (BP) neural network model demonstrated the highest and most uniform predictive performance in the downgrading, HSIL, and upgrading groups, with areas under the curve (AUCs) of 0.90, 0.84, and 0.69; sensitivities of 0.74, 0.84, and 0.42; specificities of 0.90, 0.71, and 0.95; and accuracies of 0.74, 0.84, and 0.95, respectively. In the external testing set, the BP neural network model showed a higher predictive performance than the logistic regression model, with an overall AUC of 0.91. Therefore, a web‐based prediction tool was developed in this study. BP neural network prediction model has excellent predictive performance and can be used for the risk stratification of patients with CDB‐diagnosed HSIL. [ABSTRACT FROM AUTHOR]

Introduction: DNA methylation-based biomarkers have been investigated as useful tools in the carcinogenesis process, including the triage of HPV-associated cancers. In this context, we conducted a systematic review and meta-analysis focused on evaluating the changes in the level of DNA methylation in cases of pre-cancerous (i.e., anal intraepithelial neoplasia, AIN-1, -2., -3) and cancerous (i.e., squamous cell carcinoma, SCC) anal lesions. Methods: A research in the PubMed, Scopus, and Web of Science databases was carried out, following the PRISMA 2020 protocol, using the following keywords: "anal cancer", "anal intraepithelial neoplasia", "methylation", and "epigenetic". All observational studies that reported the level of DNA methylation by grade of anal lesions and for different target genes were included. The QUADAS-2 tool was used to assess the studies' quality, whereas pooled prevalence, sensitivity, specificity, and diagnostic odds ratio (DOR) were employed to verify the accuracy of the test in the detection of high-grade lesions. Results: Eight studies met the inclusion criteria, involving a total of 1555 clinical samples. The prevalence of methylation-positive samples by histological grading was 27%, 45%, 54%, and 98% for AIN1, AIN2, AIN3, and SCC, respectively. Similar results were observed for the DOR, with higher ORs in more severe lesions. The pooled AUC (95%CI) for the diagnosis of ≥AIN2 was 0.68 (0.63–0.73). Conclusions: The present review and meta-analysis support the introduction of DNA methylation-based biomarkers in the triage of subjects with low-grade anal lesions and in the monitoring of treatment outcomes. Standardized protocols and a prospective study design are needed to implement methylation tests in clinical practice. [ABSTRACT FROM AUTHOR]

Low‐grade cervical intraepithelial neoplasia (CIN1) is an early stage of cervical cancer development. Previously, we reported that exposure to polycyclic aromatic hydrocarbons (PAHs) increases the risk of cervical precancerous lesions, especially in females with a high‐risk human papillomavirus (HR‐HPV) infection. However, the effects of PAHs on CIN1 progression remain unclear. A community‐based prospective cohort study was conducted to evaluate the role of exposure to PAHs in the progression of CIN1. A total of 564 patients diagnosed with CIN1 were followed‐up at 6, 12, and 24 months, post‐diagnosis, to determine CIN1 reversion, persistence, and progression. Exposure to PAHs was determined by the urine 1‐hydroxipayrene (1‐OHP) level. Our results showed that the 1‐OHP level was significantly higher in patients with CIN1 persistence/progression than in those with reversion (P <.05). High exposure to PAHs increased the risk of CIN1 persistence/progression, with hazard ratios (HR), 95% confidence intervals (CI) of (1.62, 1.24–2.67), (1.98, 1.42–2.75), and (2.37, 1.61–3.49) at 6, 12, and 24 months, post‐diagnosis, respectively. The effect was enhanced with HR‐HPV positivity, as determined at 6 (1.82, 1.24–2.67), 12 (3.02, 1.74–5.23), and 24 (2.51, 1.48–4.26) months, post‐diagnosis. Moreover, the predictive value of exposure to PAHs for CIN1 persistence/progression was higher in HR‐HPV‐positive patients than in HR‐HPV‐negative patients. The results revealed that exposure to PAHs facilitated the malignant progression of CIN1 and hindered its reversal, particularly in patients with HR‐HPV infection. Our findings provide novel insights into early prevention and intervention targeting the initiation and progression of cervical neoplasia. [ABSTRACT FROM AUTHOR]

ABSTRACT Objective Design Setting/Sample Methods Main Outcome Measures Results Conclusion To compare the performance of cytology, HPV16/18 genotyping and PAX1/SOX1 methylation for the triage of high‐risk HPV‐positive cervical samples.Retrospective analyses of archival samples collected from a large‐scale prospective randomised controlled trial.HPV‐positive women recruited from the general cervical screening population.403 HPV‐positive samples including 113 normal, 173 low‐grade cervical intraepithelial neoplasia (LG‐CIN), 114 HG‐CIN and three cervical cancers. All samples were assessed by liquid‐based cytology, HPV genotyping and PAX1/SOX1 methylation.AUC (area under the curve), sensitivity and specificity for cytology, HPV16/18 genotyping and PAX1/SOX1 methylation for high‐grade (HG) premalignant cervical lesions.PAX1 was more sensitive than cytology and HPV16/18 genotyping in detecting a HG lesion (CIN2+). The sensitivity for PAX1, SOX1, cytology and HPV16/18 were 73.5% (95% CI: 65.5–81.5), 41.9% (95% CI: 32.9–50.8), 48.7% (95% CI: 39.7–57.8) and 36.8% (95% CI: 28.0–45.5), respectively, and their respective specificities were 70.3% (95% CI: 65.0–75.6), 83.6% (95% CI: 79.3–87.9), 77.6% (95% CI: 72.8–82.5) and 67.1% (95% CI: 61.7–72.6), respectively. Overall, PAX1 gave the best AUC at 0.72. Adding SOX1 to PAX1 did not improve the AUC (0.68). Three hundred and twenty‐two women who did not have a HG lesion at baseline were followed up for two rounds of screening. Fewer women developed a HG lesion with a normal baseline PAX1 compared to women with a normal baseline cytology or negative HPV16/18 (8.4% vs. 14.5% and 17.5%, respectively).PAX1 triage for referral to colposcopy in HPV‐positive women may be superior to cytology and HPV16/18 genotyping. [ABSTRACT FROM AUTHOR]

Introduction: We report head-to-head comparison of the bivalent and quadrivalent HPV vaccine efficacies against immediate precursors of cervical cancer from 15 years' country-wide cancer registry follow-up of phase III trial cohorts and an age-aligned cohort of unvaccinated women. Methods: These individually and/or clusterrandomized cohorts of HPV6/11/16/18- and HPV16/18-vaccinated and unvaccinated women were enrolled, respectively, in 2002, 2004, and 2003/2005. The trial cohorts comprised initially 16- to 17-yearold HPV6/11/16/18-vaccinated FUTURE II (NCT00092534) participants (866) and HPV16/18-vaccinated PATRICIA (NCT00122681) and 012 trial (NCT00169494) participants (2,465), and 16,526 initially 16- to 19-year-old unvaccinated controls. After active 4-year clinical follow-up, passive, country-wide Finnish Cancer Registry (FCR) follow-up for cervical intraepithelial neoplasia grade 3 (CIN3) and adenocarcinoma in situ (AIS) was based on consented use of unique personal identifiers and started 6 months after the end of the FUTURE II and PATRICIA trials in 2007 and 2009, and ended at the end of 2019. The follow-up with altogether 229,020 follow-up years was age-aligned to ensure that similarly aged cohorts were passively followed up for 15 years post=vaccination for the intention-to-treat analyses of vaccine efficacy. Results: Overall, we identified 5 and 16 CIN3 (no AIS) cases in the HPV6/11/16/18 and HPV16/18 cohorts, respectively, during the FCR-based follow-up. In the unvaccinated cohort, we identified 281 CIN3 cases, 20 AIS cases, and 13 cases with invasive cervical cancer. Vaccine efficacies against CIN3+ were 68.4% and 64.5% for the quadrivalent and the bivalent vaccines, respectively, with overlapping confidence intervals. Discussion: Long-term follow-up of randomized, initially adolescent HPVvaccinated and unvaccinated cohorts shows, in this head-to-head setting, that the bivalent and quadrivalent HPV vaccines are equally effective against immediate precursors of cervical cancer. [ABSTRACT FROM AUTHOR]

Introduction: The management of patients with low-grade cervical intraepithelial neoplasia (CIN1) remains controversial. We analyzed the pathological upgrading rates of patients with CIN1 undergoing conization, identifying influencing factors, and compared their outcomes to those of patients with CIN1 receiving follow-up only. Methods: This retrospective study included 466 patients with CIN1 confirmed by histopathology and treated with conization. Postoperative pathological upgrading was determined and its influencing factors were identified. We also analyzed post-conization outcomes, examining the rate of persistent/recurrent CIN1 and its influencing factors, and comparing these results to those of patients receiving follow-up only. Results: The pathological upgrading rate of patients with CIN1 after conization was 21.03% (98/466), and the influencing factors were preoperative high-risk human papillomavirus (HR-HPV) infection and cytological results. The upgrading rates of HR-HPV positive and negative patients were 22.05% and 0.00%, respectively (χ² = 5.03, P=0.03). The upgrading rate of patients with cytological results negative for intraepithelial lesion malignancy was 10.94%, while the upgrading rates of atypical squamous cells, cannot exclude high-grade lesion(ASC-H) and high-grade squamous intraepithelial lesion(HSIL) groups were 47.37% and 52.94%, respectively (χ² = 22.7, P=0.03). Persistent/recurrent CIN1 rates in the conization group were 21.24%, 15.97%, and 6.67% at 6, 12, and 24 months, respectively, significantly lower than those in the follow-up only group. The CIN2 progression rate in the conization group (0.26%) during the 24-month follow-up period was also significantly lower than that in the follow-up only group (15.15%; χ² = 51.68, P<0.01). The only factor influencing postoperative persistent/recurrent CIN1 was preoperative HR-HPV status. No patients who were HR-HPV negative preoperatively exhibited persistent/recurrent CIN1, compared with 25.55% of those who were HR-HPV positive preoperatively (χ² = 4.40, P=0.04). Discussion: The risk of progression to CIN2+ in the medium term is higher in patients with CIN1 receiving follow-up than in those undergoing conization. Doctors should refer to the guidelines but comprehensively consider age, fertility requirements, preoperative HR-HPV and cytological results, follow-up conditions, and other factors to select the most appropriate treatment strategy for patients with CIN1. [ABSTRACT FROM AUTHOR]

Background: The prognostic significance of Treg and Th17 cells, as well as their ratio (Th17/Treg), in cervical cancer remains a topic of debate. Our study aimed to clarify their association with patient survival and clinical outcomes in cervical cancer through a comprehensive meta-analysis. Materials and methods: We conducted a comprehensive search in PubMed, Embase, and Web of Science to identify eligible studies. Studies related to cervical cancer and involving Treg cells or Th17 cells were included. For prognostic analysis, we collected Hazard Ratio values of patient survival. For studies focusing on clinical characteristics, we selected mean and standard deviation values for further analysis. This study was registered at PROSPERO (ID:CRD42024546507). Results: Out of the 2949 records initially retrieved, we ultimately included 21 studies in our analysis. High levels of Treg cells were found to be correlated with shorter survival in patients with cervical cancer. Subgroup analysis revealed that the prognostic effect of Treg cells on cervical cancer was not influenced by their source or definition. However, analyses of different survival measures indicated that only Overall Survival showed a correlation with Treg cell levels. Additionally, Treg cells were associated with clinical staging. High-grade Th17 cells were associated with lymphatic metastases and advanced clinical stage. The Th17/Treg ratio was found to be elevated in both cervical intraepithelial neoplasia and cervical cancer patients compared to controls. Discussion: Despite limitations such as heterogeneity among selected studies and inadequate subgroup analyses, our study contributes to a deeper understanding of the significance of Treg cells in the onset and progression of cervical cancer. It also provides valuable insights for future research in immunotherapy. [ABSTRACT FROM AUTHOR]

Background: The risk of cervical cancer progression in high-risk human papillomavirus (HR-HPV)-positive women is associated with cervical lesion severity and molecular heterogeneity. Classification systems based on p16 and Ki67 expression cumulative scores (0–3 each)—p16/Ki67 collectively known as an immunoscore [IS]—are an accurate and reproducible method for grading cervical intraepithelial neoplasia (CIN) lesions. Meanwhile, DNA methylation is an early event in the development of cervical cancer. Hence, this study evaluated the relationship among CIN, p16/Ki-67 IS, and PAX1/ZNF582 methylation. Methods: In this study, 414 HPV-positive paraffin-embedded specimens were collected, and PAX1/ZNF582 methylation and the p16/ki67 IS were determined. A total of 43 invalid samples were excluded and 371 were included in the statistical analyses. There were 103 cervicitis, 95 CIN1, 71 CIN2, 89 CIN3, and 13 squamous cell carcinoma (SCC) cases. The association between PAX1/ZNF582 methylation and p16/Ki6 immunohistochemical staining scores was analyzed. Results: The ΔCp of PAX1m (PAX1 methylation) and ZNF582m (ZNF582 methylation) decreased with cervical lesion severity (Cuzick trend test, all P < 0.001). The severity of the cervical lesions and p16, Ki67, and p16/Ki67 IS showed an increasing trend (Multinomial Cochran-Armitage trend test, all P < 0.001). The prevalence of PAX1m/ZNF582m increased with an increase in the IS of p16, Ki67, and p16/Ki67 (Cochran-Armitage trend test, all P < 0.001). In cervical SCC, the IS was 5–6, and the PAX1m/ZNF582m was positive. Meanwhile, heterogeneity was observed in CIN lesions: 10 cases had an IS of 3–4 and were PAX1m/ZNF582m-positive in ≤ CIN1; 1 case had an IS of 0–2 and was PAX1m/ZNF582m-positive in CIN2/3. Conclusions: Significant heterogeneity was observed in CIN lesions for p16 and Ki67 immunohistochemical staining scores and PAX1/ZNF582 methylation. This may help clinicians personalize the management of CIN based on the predicted short-term risk of cancer progression, minimizing the rate of missed CIN1 diagnoses and incorrect treatment of CIN2/3. [ABSTRACT FROM AUTHOR]

Background Due to the heterogeneity of risk for invasive anal cancer (IAC) among people with human immunodeficiency virus (PWH), we investigated predictors of IAC and described outcomes among those with a cancer diagnosis. Methods Using a longitudinal inception cohort of anal cancer screening, we evaluated risk factors and outcome probabilities for incident IAC in Cox models. Screening included anal cytology and digital anorectal examination, and, if results of either were abnormal, high-resolution anoscopy. Results Between 30 November 2006 and 3 March 2021, a total of 8139 PWH received care at the University of California, San Diego, with 4105 individuals undergoing screening and subsequently followed up over a median of 5.5 years. Anal cancer developed in 33 of them. IAC was more likely to develop in patients with anal high-grade squamous intraepithelial lesions (aHSILs) on initial or subsequent follow-up cytology (hazard ratio, 4.54) and a nadir CD4 cell count ≤200/µL (2.99). The joint effect of aHSILs and nadir CD4 cell count ≤200/µL amplified the hazard of IAC by 9-fold compared with the absence of both. PWH with time-updated cytology aHSIL and CD4 cell counts ≤200/µL had 5- and 10-year probabilities of IAC of 3.40% and 4.27%, respectively. Twelve individuals with cancer died, 7 (21% of the total 33) due to cancer progression, and they had clinical stage IIIA or higher cancer at initial diagnosis. Conclusions PWH with both aHSIL and a nadir CD4 cell count ≤200/µL have the highest risk of IAC. PWH who died due to IAC progression had clinical stage IIIA cancer or higher at diagnosis, highlighting the importance of early diagnosis through high-resolution anoscopic screening. [ABSTRACT FROM AUTHOR]

Objectives: Optical coherence tomography (OCT) has recently been used in gynecology to detect cervical lesions in vivo and proven more effective than colposcopy in clinical trials. However, most gynecologists are unfamiliar with this new imaging technique, requiring intelligent computer-aided diagnosis approaches to help them interpret cervical OCT images efficiently. This study aims to (1) develop a clinically-usable deep learning (DL)-based classification model of 3D OCT volumes from cervical tissue and (2) validate the DL model's effectiveness in detecting high-risk cervical lesions, including high-grade squamous intraepithelial lesions and cervical cancer. Method: The proposed DL model, designed based on the convolutional neural network architecture, combines a feature pyramid network (FPN) with texture encoding and deep supervision. We extracted, represent, and fused four-scale texture features to improve classification performance on high-risk local lesions. We also designed an auxiliary classification mechanism based on deep supervision to adjust the weight of each scale in FPN adaptively, enabling low-cost training of the whole model. Results: In the binary classification task detecting positive subjects with high-risk cervical lesions, our DL model achieved an 81.55% (95% CI, 72.70–88.51%) F1-score with 82.35% (95% CI, 69.13–91.60%) sensitivity and 81.48% (95% CI, 68.57–90.75%) specificity on the Renmin dataset, outperforming five experienced medical experts. It also achieved an 84.34% (95% CI, 74.71–91.39%) F1-score with 87.50% (95% CI, 73.20–95.81%) sensitivity and 90.59% (95% CI, 82.29–95.85%) specificity on the Huaxi dataset, comparable to the overall level of the best investigator. Moreover, our DL model provides visual diagnostic evidence of histomorphological and texture features learned in OCT images to assist gynecologists in making clinical decisions quickly. Conclusions: Our DL model holds great promise to be used in cervical lesion screening with OCT efficiently and effectively. [ABSTRACT FROM AUTHOR]

Background: Cervical cancer is the leading cause of cancer deaths in Gambian women. Current estimates indicate that 286 women are annually diagnosed with cervical cancer with a fatality rate of 70%. In an attempt to address this, in 2019 the quadrivalent HPV vaccine was incorporated into the Gambia's Expanded Programme on Immunisation. The study aims to retrospectively assess the prevalence and distribution of high-risk HPV genotype in archived, formalin fixed paraffin embedded cervical biopsy tissues diagnosed with cervical cancer in the Gambia from year 2013–2022. Method: A total of 223 samples with histologically diagnosis of cervical cancer with adequate tissues were sectioned and deparaffinised, followed by HPV DNA extraction and the detection of HR-HPV by real-time multiplex PCR. The human β-globin gene was amplified in 119 samples, which were subsequently tested for HPV DNA. Results: HPV was prevalent in 87.4% (104 of 119) cervical cancer cases, 12.6% (15/119) samples tested negative. Amongst cervical cancer cases, HPV 16 genotype was the most frequent type accounting for 53.8% (56 /104), followed by other HR-HPV genotypes 17.3% (18/104), and HPV genotype 18 was 15.4% (16/104). Furthermore, multiple HPV infections involving HPV 16 and /or 18 was detected in 14 cases as follows: HPV genotypes 16 and 18 (3.8%, 4 /104), HPV 16 and other HR-HPV (6.7%, 8/104), and HPV 18 and other HR-HPV (1.9%, 2/104). A significant association between age and diagnosis with cervical cancer (p = 0.02), and HPV genotype 16 (p = 0.04) was observed. Conclusion: There was no difference in the distribution of HPV 16 and 18 genotypes in cervical cancer cases in The Gambia in comparison with the global distribution. However, the high prevalence of cervical cancer cases with other HR-HPV, and combined infections of HPV 16 with other HR-HPV genotypes seen in this study, clearly shows that the nonavalent HPV vaccine could be more beneficial for The Gambia. This study provides The Gambia with a baseline data to use in policy decisions regarding future evaluation of the quadrivalent HPV vaccine in the country. [ABSTRACT FROM AUTHOR]

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 SPF10-DEIA-LiPA25 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. [ABSTRACT FROM AUTHOR]

Objective Methods Results Conclusions To explore the effectiveness of HPV 16/18 E7 oncoprotein in detecting high‐grade cervical intraepithelial neoplasia (CIN) and predicting disease outcomes in HPV 16/18‐positive patients.The present study was a cross‐sectional study with a 2‐year follow up. We collected 915 cervical exfoliated cell samples from patients who tested positive for HPV 16/18 in gynecologic clinics of three tertiary hospitals in Beijing from March 2021 to October 2022 for HPV 16/18 E7 oncoprotein testing. Subsequently, 2‐year follow up of 408 patients with baseline histologic CIN1 or below were used to investigate the predictive role of HPV 16/18 E7 oncoprotein in determining HPV persistent infection and disease progression.The positivity rate of the HPV 16/18 E7 oncoprotein assay was 42.06% (249/592) in the inflammation/CIN 1 group and 85.45% (277/324) in the CIN2+ group. For CIN2+ detection, using the HPV 16/18 E7 oncoprotein assay combined with HPV 16/18 testing, the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were 85.45%, 57.94%, 52.57%, and 87.95%, respectively. During the 2‐year follow up, the sensitivity, specificity, PPV, and NPV for predicting persistent HPV infection were 48.44%, 58.21%, 34.64%, and 71.18% in the baseline inflammation and CIN1 group.As a triage method for high‐grade CIN screening in HPV 16/18‐positive patients, HPV 16/18 E7 oncoprotein demonstrated a relatively high NPV, making it suitable for clinical use in triaging HPV 16/18‐positive cases and potentially reducing the colposcopic referral rate. HPV 16/18 E7 oncoprotein exhibited a preferably predictive value in determining HPV infection outcomes and disease progression. [ABSTRACT FROM AUTHOR]

Despite widespread cervical cancer (CC) screening programs, low participation has led to high morbidity and mortality rates, especially in developing countries. Because early-stage CC often has no symptoms, a non-invasive and convenient diagnostic method is needed to improve disease detection. In this study, we developed a new approach for differentiating both CC and cervical intraepithelial neoplasia (CIN)2/3, a precancerous lesion, from healthy individuals by exploring CC fatty acid metabolic reprogramming. Analysis of public datasets suggested that various fatty acid metabolizing enzymes were expressed at higher levels in CC tissues than in normal tissues. Correspondingly, 11 free fatty acids (FFAs) showed significantly different serum levels in CC patient samples compared with healthy donor samples. Nine of these 11 FFAs also displayed significant alterations in CIN2/3 patients. We then generated diagnostic models using combinations of these FFAs, with the optimal model including stearic and dihomo-γ-linolenic acids. Receiver operating characteristic curve analyses suggested that this diagnostic model could detect CC and CIN2/3 more accurately than using serum squamous cell carcinoma antigen level. In addition, the diagnostic model using FFAs was able to detect patients regardless of clinical stage or histological type. Overall, the serum FFA diagnostic model developed in this study could be a powerful new tool for the non-invasive early detection of CC and CIN2/3. [ABSTRACT FROM AUTHOR]

BACKGROUND: Cervical cancer (CC) is a common female malignancy, with a global incidence rate second only to breast cancer. OBJECTIVE: To propose a new idea for early treatment and auxiliary diagnosis of CC by exploring the diagnostic and prognostic implications of serum miR-182 in CC. METHODS: We enrolled 70 CC patients, 35 cervical intraepithelial neoplasia (CIN) patients and 35 healthy controls (HCs), who visited The First Affiliated Hospital of Hainan Medical College Hospital between January 2015 and April 2016. miR-182 expression was quantified by real-time quantitative PCR and compared among the three groups. The correlation of serum miR-182 expression with patients' clinical features was evaluated. The receiver operating characteristic curve (ROC) and the Kaplan-Meier method were used to evaluate the early diagnostic value and prognostic value of serum miR-182. Cox regression analysis was performed to determine serum miR-182 expression and its important role in predicting CC patients' prognosis. RESULTS: Serum miR-182 expression was determined to be 0.345 ± 0.094, 0.369 ± 0.076, and 0.586 ± 0.157 in CC patients, CIN patients, and HCs, respectively (P < 0.001). Serum miR-182 expression had an obvious association with lymph node metastasis and pathological differentiation (P < 0.05). The area under the ROC curve (AUC) of serum miR-182 was 0.709 (95% CI: 0.622–0.795), the critical value was 0.456, the sensitivity was 81.4%, and the specificity was 52.9%. CC patients were grouped as either the low- (miR-182 < 0.3) or high-level group (miR-182 ⩾ 0.03) based on serum miR-182 levels, and a Cox regression model of OS was established. Serum miR-182 expression was identified as a factor independently influencing CC patients' OS (P = 0.028); the death risk of the high-level group was 3.246 times that of the low-level group. CONCLUSION: Serum miR-182 expression is not only a biomarker for early diagnosis of CC, but also one of the independent factors influencing the survival and prognosis of CC patients. [ABSTRACT FROM AUTHOR]

Simple Summary: Women treated for cervical precancers (CIN2/3) have an increased risk for recurrent lesions and therefore require post-treatment monitoring. Standard follow-up care based on hrHPV-DNA/cytology co-testing has high sensitivity but limited specificity. Host cell methylation correlates highly with CIN2/3 and may thus be a more suitable marker than hrHPV, particularly since HPV infection is not confined to women with the disease. Here, we show that in combination with cytology, the methylation markers comprising GynTect® are as sensitive as hrHPV for the detection of recurrent CIN2/3 lesions but are more specific. A reduction in the rate of false positive results would not only be more cost-effective but may also reduce the number of women requiring re-treatment. These findings must be verified in a sufficiently large validation study. Post-treatment follow-up in women with CIN3 is mandatory due to relapse in up to 15% of patients within 2 years. Standard follow-up care based on hrHPV-DNA/cytology co-testing has high sensitivity but limited specificity. The aim of our proof-of-concept case-control study was to evaluate the performance of the methylation test GynTect® for the detection of recurrent CIN2/3 during follow-up. Residual clinical material from a recent, prospective, multicenter, observational study was available for further analysis. We studied a sample of 17 cases with recurrent CIN2/3 diagnosed within 24 months of follow-up and 31 controls without recurrence. DNA from cervical scrapes at baseline (immediately before CIN3 surgery) and up to three follow-up visits were analyzed for hrHPV and GynTect® methylation status. Cytology data were available from the previous study. Overall, 12 cases and 21 controls were GynTect-positive at baseline. In these subgroups, single test sensitivity at first follow-up was 67% (95% CI 39–87%) for GynTect® compared to 83% (95% CI 55–96%) for hrHPV (p = 0.50). Single test specificity was significantly higher for GynTect® (90%, 95% CI 71–98% vs. 62%, 95% CI 40–80%) (p = 0.03). In a co-testing setting, both hrHPV/cytology and GynTect®/cytology detected all recurrences. Specificity for GynTect®/cytology was higher than for hrHPV/cytology, but this difference was not statistically significant. In conclusion, for initially GynTect-positive patients, both hrHPV and GynTect® tests detected recurrent disease with similar sensitivity, but the GynTect® assay has a higher specificity. Incident hrHPV infection and/or persisting multifocal hrHPV infections without clinical disease are most likely responsible for the poorer specificity of the hrHPV test. A future prospective validation study will have to show whether GynTect®/cytology co-testing can outperform hrHPV/cytology co-testing in post-treatment surveillance. [ABSTRACT FROM AUTHOR]

Cervical cancer related to high-risk human papillomavirus (HR-HPV) is the second female cancer in Mauritania (Northwest Sahelian Africa). We assessed the distribution of HPV genotypes in Mauritanian women with high-grade cervical intraepithelial neoplasia (CIN2/3) or invasive cervical cancer (ICC). A prospective study was conducted in the Centre Hospitalier National, Nouakchott, Mauritania, to collect cervical biopsies among women suspected of CIN2/3 or cancer. HPV DNA detection and genotyping were carried out from formalin-fixed, paraffin-embedded biopsies using multiplex PCR (Human Papillomavirus Genotyping Real-Time PCR Kit, Bioperfectus Technologies Co., Taizhou, China). Fifty biopsies were included from women (mean age: 56.7 years) suffering from CIN2/3 (28.0%) and ICC (72.0%) which corresponded to 32 (64.0%) squamous cell carcinomas (SCC) and 4 (8.0%) adenocarcinomas (ADC). HPV DNA detection was successful in 47 (94.0%) samples. The most prevalent HR-HPV genotypes were HPV-45 (40.4%), HPV-16 (38.3%), HPV-39 and HPV-52 (23.4%), HPV-33 (17.0%), HPV-18 (14.9%), HPV-35 (4.2%), and HPV-56 (2.1%). The majority (93.6%) of HPV-positive biopsies contained at least one HPV type covered by the 9-valent Gardasil-9® vaccine, and 40.9% were infected by multiple vaccine HPV genotypes. To eradicate cervical cancer in Mauritania, prophylactic HPV vaccination must be combined with primary molecular screening of cervical HR-HPV infection. [ABSTRACT FROM AUTHOR]

Implementation of primary human papillomavirus (HPV) testing has been slow in the United States perhaps because of concerns of decreased sensitivity compared with concurrent HPV and cytology testing ("cotesting"). We used the National Breast and Cervical Cancer Early Detection Program and the Kaiser Permanente of Northern California cohort to quantify potential trade-offs with primary HPV compared with cotesting in 4 US populations with differing precancer or cancer prevalence. In all settings, cotesting required more lab tests and more colposcopies compared with primary HPV testing. Additional cervical intraepithelial neoplasia grade 3 or cancer immediately detected from cotesting vs primary HPV decreased with decreasing population-average cervical intraepithelial neoplasia grade 3 or cancer prevalence from 71 per 100 000 screened among never or rarely screened individuals in the National Breast and Cervical Cancer Early Detection Program (prevalence = 1212 per 100 000) to 4 per 100 000 screened among individuals with prior HPV-negative results in Kaiser Permanente of Northern California (prevalence = 86 per 100 000). These data suggest that cotesting confer an unfavorable benefit-to-harm ratio over primary HPV testing. [ABSTRACT FROM AUTHOR]

Human papillomavirus (HPV) infections are common among reproductive-age women. The use of primary HPV testing has proven more effective in identifying high-grade precancerous lesions, leading to better clinical outcomes in women. HPV integration into the host genome is a multifactorial process. Various host, viral, and environmental cofactors, such as smoking, cervicovaginal microbiota, estrogen levels, and coinfection with HIV, influence this process. The disruption of the E2 gene is identified as a hallmark of HPV integration and cancer development, leading to the overexpression of oncogenic proteins (E6/E7) and the formation of superenhancers, thereby contributing to cellular transformation and cervical neoplasia. HPV integration results in host genomic instability, chromosomal rearrangements, loss of function in tumor suppressor genes, and epigenome dysregulation. Countless efforts have been made to eradicate cervical cancer worldwide, including improving disease screening and human papillomavirus (HPV) vaccination programs. Nevertheless, cervical cancer still claims the lives of more than 300 000 women every year. Persistent infections with high-risk HPV genotypes 16 and 18 are the main cause of cancer and may result in HPV integration into the host genome. The central dogma is that HPV integration is an important step in oncogenesis, but in fact, it impedes the virus from replicating and spreading. HPV causing cervical cancer can therefore be perceived as a failed evolutionary viral trait. Here we outline the occurrence and mechanisms of HPV integration and how this process results in oncogenic transformation. [ABSTRACT FROM AUTHOR]

Objective: To compare the cost‐effectiveness of different treatments for cervical intraepithelial neoplasia (CIN). Design: A cost‐effectiveness analysis based on data available in the literature and expert opinion. Setting: England. Population: Women treated for CIN. Methods: We developed a decision‐analytic model to simulate the clinical course of 1000 women who received local treatment for CIN and were followed up for 10 years after treatment. In the model we considered surgical complications as well as oncological and reproductive outcomes over the 10‐year period. The costs calculated were those incurred by the National Health Service (NHS) of England. Main outcome measures: Cost per one CIN2+ recurrence averted (oncological outcome); cost per one preterm birth averted (reproductive outcome); overall cost per one adverse oncological or reproductive outcome averted. Results: For young women of reproductive age, large loop excision of the transformation zone (LLETZ) was the most cost‐effective treatment overall at all willingness‐to‐pay thresholds. For postmenopausal women, LLETZ remained the most cost‐effective treatment up to a threshold of £31,500, but laser conisation became the most cost‐effective treatment above that threshold. Conclusions: LLETZ is the most cost‐effective treatment for both younger and older women. However, for older women, more radical excision with laser conisation could also be considered if the NHS is willing to spend more than £31,500 to avert one CIN2+ recurrence. [ABSTRACT FROM AUTHOR]

Introduction: Active surveillance for cervical intraepithelial neoplasia grade 2 (CIN2) has been implemented recently in many countries, including the Nordic countries. In Denmark, the only eligibility criterion for active surveillance for CIN2 is that the woman should be of reproductive age. With this study, we aimed to evaluate clinical and socioeconomic characteristics in women with CIN2 managed by active surveillance or large loop excision of the transformation zone (LLETZ) and to evaluate temporal changes in the clinical management of CIN2. Material and Methods: We conducted a Danish nationwide study using data from healthcare registries. All female residents aged 18–40 years, diagnosed with incident CIN2 from January 1, 1998, to February 29, 2020, were included. We collected data on age, index cytology result, year of CIN2 diagnosis, region of residence, civil status, HPV vaccination status, and socioeconomic position indicators. The variables were tabulated overall and by management group (active surveillance vs. LLETZ). To evaluate time trends, we used joinpoint regression to calculate the annual percentage change (APC), including 95% confidence intervals (CI). Results: Of the 27 536 women with CIN2 included, 12 500 (45.4%) underwent active surveillance, and 15 036 (54.6%) underwent a LLETZ. Women undergoing active surveillance were younger, more often HPV‐vaccinated, and more likely to have a normal/low‐grade index cytology result than women undergoing LLETZ. Socioeconomic position indicators did not differ. Over time, the proportion of women undergoing active surveillance increased from 21.7% in 2004 to 73.6% in 2019 (APC 9.7, 95% CI 8.1–11.4). The proportion of women undergoing active surveillance aged <30 declined over time (APC −2.2, 95% CI −2.9 to −1.5). The proportion of women with normal/low‐grade index cytology increased slightly to 51.6% in 2019 (APC 0.8, 95% CI 0.4–1.3). Conclusions: The use of active surveillance for CIN2 has increased over the past two decades in Denmark. Observed differences in characteristics between women undergoing active surveillance vs LLETZ are likely related to indications for clinical management. [ABSTRACT FROM AUTHOR]

Introduction: In Denmark, where human papillomavirus (HPV) ‐based cervical cancer screening is being implemented, the aim of this pilot implementation study was to test a specific screening algorithm, assess follow‐up examination attendance, and measure the proportion of precancer lesions found in relation to the number of women referred for colposcopy. Material and Methods: From May 2017 to December 2020, 36 417 women in the uptake area of the Department of Pathology, Vejle Hospital, Region of Southern Denmark, were included in the HPV group. Women positive for HPV16/18 irrespective of cytology and women positive for other high‐risk HPV (hrHPV) types having concomitant abnormal cytology were referred directly to colposcopy. Women positive for other hrHPV types and normal cytology were referred to repeat screening after 12 months, and hrHPV negative to routine screening after three years. We obtained information on screening results and subsequent histological diagnosis from the Danish Pathology Databank through September 2022. Results: 3.6% of the women were referred to colposcopy after primary screening, 5% to repeat screening after 12 months, and 91.4% back to routine screening. High follow‐up rates were observed: 96% attended colposcopy after primary screening, with 91% attending colposcopy after repeat screening. CIN3+ was detected at colposcopy following the primary screening in 28.1% of HPV16/18‐positive women and 18.2% of those positive for other hrHPV types with concomitant abnormal cytology. Of the women with other hrHPV and simultaneous ASCUS/LSIL, 8% had CIN3+. At the repeat screening, 43% had become hrHPV negative, 55% were persistently positive for other hrHPV, and 2% had turned positive for HPV16/18. At the colposcopy following repeat screening, 10.1% of the women positive for other hrHPV were diagnosed with CIN3+, in comparison with 11.1% of the HPV16/18‐positive women. Conclusions: In this pilot implementation study, an algorithm for HPV‐based screening was evaluated in a Danish setting. The results demonstrated high attendance at follow‐up examinations and provided insights into the number of colposcopy referrals and the detection of CIN2 and CIN3+ cases. The results suggest that women testing positive for other hrHPV in combination with ASCUS/LSIL at primary screening could potentially be referred to repeat screening instead of an immediate colposcopy. [ABSTRACT FROM AUTHOR]

Introduction: Colposcopy is an important part of the diagnostic work‐up of women with an abnormal cervical screening test as it is used to guide the collection of biopsies. Although quality assurance has been used in the evaluation of screening programs, not much is known about quality indicators for the diagnostics and treatment of screen‐positive women. Therefore, the European Federation for Colposcopy developed quality indicators aiming to support colposcopy practice across Europe. We performed a survey of colposcopy cases to determine if the quality indicators are understandable, relevant, and reproducible. Material and Methods: We conducted a survey among all members of the European Federation for Colposcopy Quality and Standards Group from November 2022 to March 2023. Members were asked to collect information on a total of 17 quality indicators for 50 women who had been newly referred for colposcopy due to an abnormal screening test between January 1, 2020 to December 31, 2021. Results were reported descriptively. Results: We included data on 609 cases from 12 members across Europe. The majority of the quality indicators were either achieved or within reach of the agreed standard, often due to few countries with outlying data. One quality indicator had very low performance, although stratified results indicated that two countries had different clinical management of the patient type thereby skewing the results. In addition, discrepancies between the number of cases included in each quality indicator raised concerns regarding potential misunderstanding of the quality indicator and its objective. Conclusions: Quality indicators on colposcopy must be understandable to those collecting data, highlighting the importance of validating quality indicators before data collection. [ABSTRACT FROM AUTHOR]