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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.

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BACKGROUND: Cervical intraepithelial neoplasia (CIN) represents a premalignant state presumably related to perturbations in circulating levels of trace elements. MATERIALS AND METHODS: Employing inductively coupled plasma mass spectrometry (ICP-MS), we quantified essential and toxic trace elements in the sera of 60 women diagnosed with CIN and 60 age-matched healthy counterparts. RESULTS: Our investigation revealed a noteworthy higher levels in serum of Mn, Zn, and Pb, as well as lower levels in Ni, Se, Rb, and Mo levels within the CIN cohort. Levels of Mn, Zn, and Pb were higher by approximately 5.5-fold, 3.0-fold, and 7.5-fold, respectively, while Mo levels exhibited an approximate 4.5-fold reduction in CIN sera compared to the control group. While the study provided valuable insights into trace element variations, it's important to note that the adult Serbian population is considered Zn-deficient, so the Zn data should be interpreted with caution. Age stratification (30-40 vs. 40-50 vs. 50-60 years), smoking status (smokers vs. nonsmokers), and CIN severity (CIN 2 vs. CIN 3) yielded no significant disparities in elemental profiles. Among the 10 proposed ratios, 5 demonstrated a significant surge in CIN sera relative to controls: Mn/Se, Mn/Mo, Zn/Se, Zn/Mo, and Se/Mo. Correlation analysis of trace element levels revealed a predominantly consistent pattern between CIN cases and healthy subjects, except for Zn and its negative correlations (antagonistic interactions) with other analyzed trace elements. CONCLUSION: Our findings underscore differences in serum levels of specific trace elements in CIN cases versus controls, implicating their potential involvement in the underlying pathophysiological cascades culminating in cervical neoplasms.

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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.

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Purpose: This study aims to develop a machine learning (ML) model to predict the risk of residual or recurrent high-grade cervical intraepithelial neoplasia (CIN) after loop electrosurgical excision procedure (LEEP), addressing a critical gap in personalized follow-up care. Methods: A retrospective analysis of 532 patients who underwent LEEP for high-grade CIN at Cangzhou Central Hospital (2016-2020) was conducted. In the final analysis, 99 women (18.6%) were found to have residual or recurrent high-grade CIN (CIN2 or worse) within five years of follow-up. Four feature selection methods identified significant predictors of residual or recurrent CIN. Eight ML algorithms were evaluated using performance metrics such as AUROC, accuracy, sensitivity, specificity, PPV, NPV, F1 score, calibration curve, and decision curve analysis. Fivefold cross-validation optimized and validated the model, and SHAP analysis assessed feature importance. Results: The XGBoost algorithm demonstrated the highest predictive performance with the best AUROC. The optimized model included six key predictors: age, ThinPrep cytologic test (TCT) results, HPV classification, CIN severity, glandular involvement, and margin status. SHAP analysis identified CIN severity and margin status as the most influential predictors. An online prediction tool was developed for real-time risk assessment. Conclusion: This ML-based predictive model for post-LEEP high-grade CIN provides a significant advancement in gynecologic oncology, enhancing personalized patient care and facilitating early intervention and informed clinical decision-making.

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Background: Vaginal microbiota is involved in human papillomavirus (HPV) infection and cervical cancer (CC) progression, and the specific changes in vaginal microbial composition during this process remains uncertain. Objective: This study aimed to observe the changes in the specific composition of vaginal microorganisms in different cervical lesions and identify biomarkers at different stages of lesions. Methods: In this study we used the illumina high-throughput gene sequencing technology to determine the V4 region of 16SrRNA and observed the vaginal microbial composition in different cervical lesions. Results: The vaginal microbiota of patients with high-risk HPV infection and cervical lesions is significantly different from that of the normal population, but there is no significant difference in the richness of vaginal microbes. The diversity of vaginal species in CC patients is higher than that in high-risk HPV infection or CIN patients. The main manifestation is an increase in the diversity of vaginal microbes, a decrease in the relative abundance of cyanobacteria and Lactobacillus, and an increase in the relative abundance of dialister, peptonephila and other miscellaneous bacteria. There are characteristic vaginal biomarker in normal women, high risk HPV patients and CC patients. In detail, the biomarker in the normal group was varibaculum, the biomarker in the high-risk HPV group was saccharopolyspora, the biomarker of the CC group was the Proteobacteria, Corynebacterium, Coprococcus, Peptococcus and Ruminococcus. Conclusions: The study indicated that the compositions of vaginal microbes in different cervical lesions is different. The vaginal microbial composition has a certain diagnostic effect on healthy women, patients with high-risk HPV infection and cervical lesions. These microbes may serve as potential biomarkers for CC. It also provided an effective way for the treatment of HPV infections and cervical lesions.

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Bacterias , Microbiota , Infecciones por Papillomavirus , ARN Ribosómico 16S , Neoplasias del Cuello Uterino , Vagina , Humanos , Femenino , Vagina/microbiología , Vagina/virología , Infecciones por Papillomavirus/virología , Neoplasias del Cuello Uterino/virología , Neoplasias del Cuello Uterino/microbiología , Adulto , ARN Ribosómico 16S/genética , Bacterias/clasificación , Bacterias/aislamiento & purificación , Bacterias/genética , Persona de Mediana Edad , Secuenciación de Nucleótidos de Alto Rendimiento , Papillomaviridae/genética , Papillomaviridae/aislamiento & purificación , Adulto Joven , Cuello del Útero/virología , Cuello del Útero/microbiología , Cuello del Útero/patología

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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.

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Background: Cervical cancer disproportionately affects women in low- and middle-income countries (LMICs), which bear 90% of deaths. Current precancer treatments rely on healthcare workers who may be out of reach for many women. Development of a patient-controlled cervical precancer treatment can significantly improve access in remote areas and promote secondary prevention of cervical cancer. Methods: This is a phase I trial among 18 HIV-positive and HIV-negative women in Kenya, investigating use of artesunate vaginal pessaries as treatment for cervical precancer among women screening positive for cervical precancer who need excisional treatment. The primary objective will be the safety of self-administered artesunate pessaries. Participants will self-administer 200mg of artesunate vaginally daily for 5 days, followed by a drug-free week, repeated for a total of 4 cycles (artesunate self-administration on weeks 1, 3, 5, 7). The total study duration, including participant follow-up is 48 weeks. Safety and adherence will be assessed through review of symptom diaries and biweekly follow-ups during the treatment phase. Data analysis will include quantitative and qualitative methods. Figure 1 illustrates the study schema. Discussion: Considering the challenges associated with excisional treatments for cervical precancer in LMICs where access to care is limited, this study proposes an alternative approach using intravaginal Artesunate. This clinical trial will provide important safety and efficacy data on using artesunate as a topical therapy for both HIV-positive and HIV-negative women. Trial Registration: ClinicalTrials.gov identifier: NCT06165614.

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OBJECTIVE: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

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Aim: This study investigated RAP1 immunostaining variation in different cell types during CC progression.Methods: Paraffin-embedded cervical tissues from 101 patients were categorized into control, pre-neoplastic and neoplastic groups. RAP1 immunolocalization, HPV detection and genotyping were performed. A semiquantitative immunoreactive score was employed to compare labeling intensity, cellular localization, nuclear labeling, percentage and distribution of reactive cells.Results: 73% (72/99) of cervical specimens were HPV+. RAP1 was localized in the nucleus and cytoplasm of all samples. Cytoplasmic RAP1 immunoscore was higher than nuclear score in all CC groups. RAP1 intensity increased with lesion severity. SCC samples exhibited predominantly intense RAP1 immunostaining.Conclusion: RAP1 is an efficient biomarker for detecting invasive CC lesions but has limited utility in distinguishing SCC grades.

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[Box: see text].

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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.

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Ácidos Esteáricos , Displasia del Cuello del Útero , Neoplasias del Cuello Uterino , Humanos , Femenino , Displasia del Cuello del Útero/diagnóstico , Displasia del Cuello del Útero/sangre , Neoplasias del Cuello Uterino/sangre , Neoplasias del Cuello Uterino/diagnóstico , Ácidos Esteáricos/sangre , Adulto , Ácido 8,11,14-Eicosatrienoico/sangre , Persona de Mediana Edad , Biomarcadores de Tumor/sangre , Curva ROC

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This study assessed the relative clinical sensitivity and specificity, as well as reproducibility, for high-risk HPV types of the Roche cobas HPV test when processed using the Roche cobas 5800 system. The results from this study demonstrate that the cobas HPV test using the cobas 5800 system fulfils the Meijer criteria for use in population-based cervical screening. This clinical validation study also examines the clinical sensitivity and specificity based on partial genotyping, with separate detection of HPV16 and HPV18, compared with the Roche cobas 4800 HPV test, a second-generation standard comparator assay. The cobas HPV test has a relative clinical sensitivity of 1.000, when compared with the cobas 4800 HPV test to detect histologically confirmed CIN2+ lesions in woman aged 30 years or older, with a relative clinical specificity of 0.995. The general intra- and inter-laboratory agreement for the cobas HPV test on the cobas 5800 system for finding a HPV positive result were 99.1% and 99.6%, respectively.IMPORTANCEThis study demonstrates, for the first time, the clinical performance of the Roche cobas HPV test when processed using the new cobas 5800 system [cobas (5800)]. This study shows that the cobas (5800) demonstrates relative clinical sensitivity and specificity, when compared with a standard comparator HPV test, which meets the international HPV test validation requirements. Intra- and inter-laboratory reproducibility also fulfills these criteria. The current study demonstrates that the cobas (5800) can be used for primary HPV-based cervical screening on cervical specimens.

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CpG site methylation patterns have potential to improve differentiation of high-grade screening-detected cervical abnormalities. We assessed CpG differential methylation (DM) and differential variability (DV) in high-grade (CIN2+) vs. low-grade (≤CIN1) lesions. In ≤CIN1 (n=117) and CIN2+ (n=31) samples, cervical sample DNA underwent testing with Illumina HumanMethylation arrays. We assessed DM and DV of CpG methylation M values among nine cervical cancer-associated genes. We fit CpG-specific linear models and estimated empirical Bayes standard errors and false discovery rates (FDR). An exploratory epigenome-wide association study (EWAS) aimed to detect novel DM and DV CpGs (FDR<0.05) and Gene Ontology (GO) term enrichment. Compared to ≤CIN1, CIN2+ exhibited greater methylation at CCNA1 Cluster 1 (M value difference 0.24; 95% CI 0.04, 0.43) and RARB Cluster 2 (0.16; 95% CI 0.05, 0.28), and lower methylation at CDH1 Cluster 1 (-0.15; 95% CI -0.26, -0.04). CIN2+ exhibited lower variability at CDH1 Cluster 2 (variation difference -0.24; 95% CI -0.41, -0.05) and FHIT Cluster 1 (-0.30; 95% CI -0.50, -0.09). EWAS detected 3,534 DM and 270 DV CpGs. Forty-four GO terms were enriched with DM CpGs related to transcriptional, structural, developmental, and neuronal processes. Methylation patterns may help triage screening-detected cervical abnormalities and inform US screening algorithms.

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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.

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Objective: Analyze women treated with underwent cold knife conization (CKC) to remove advanced squamous intraepithelial lesions (CIN) of the cervix. The histopathological upgrading of the lesions previously detected on vaginal biopsy and postoperative pregnancy outcomes of were investigated, to identify high-risk subgroups in women. Methods: A retrospective study was conducted at the First Central Hospital of Baoding City from June 2019 to December 2022 to analyze confirmed cases of Cervical Intraepithelial Neoplasia CIN-II and CIN-III. Investigation of pathological changes in postoperative pathological tissues, and to perform binary logistic analysis to identify risk factors for histopathological escalation in postoperative lesions. We analyze the effects of CKC surgery on pregnancy outcomes in patients by comparing against a control group of healthy pregnant women. Results: Out of the 176 patients diagnosed with CIN-II who underwent cervical biopsy, 39 (22.16%) were found to have a final specimen diagnosis of CIN-III, while 7 (3.98%) were downgraded to CIN-I. Among the 108 patients diagnosed with CIN-III who underwent cervical biopsy, 7 cases (6.48%) were ultimately confirmed to have CIN-III. Ki67-positive, p16-positive (OR = 1.13, 95% CI 1.01-1.15), and colposcopy biopsy for CIN-II (OR = 1.59, 95% CI 1.33-3.6) were independent risk factors for pathological upgrade after CKC. Compared with healthy pregnant women, CIN patients had higher rates of premature birth (14.4%), premature rupture of the fetal membrane (13.6%), and cesarean section (37.5%) (P < 0.05). The mode of conception, abortion rate, ectopic pregnancy rate, and postpartum hemorrhage were not different between healthy pregnant women and CIN patients (P > 0.05). Conclusion: Following cervical multi-point biopsy or CKC, along with pathological examination, the accurate diagnosis of cervical lesions is crucial as it allows for more precise identification of such lesions. Additionally, CKC increases the risk of premature birth, premature rupture of membranes, and the need for cesarean section.

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Biomarkers including Forkhead/winged-helix transcription factor box P3 have been proposed in immunohistochemical techniques to diagnose cervical lesions, but can be objectively quantified and measured in blood using methods that can be standardised. In this study we quantified the serum FOXP3 concentrations and assessed their association with cervical lesions at the cervical cancer clinic of Mbarara Regional Hospital (MRRH) Southwestern Uganda. We performed secondary analysis on archived serum samples from a previous unmatched case control study in which we recruited 90 cervical cancer (CC) cases, 90 cervical intraepithelial neoplasia (CIN) cases before any form of treatment and 90 controls. Clinical and demographic data were recorded. We measured FOXP3 concentrations using quantitative ELISA. We performed descriptive statistics and logistic regression in STATA 17 and took P-values of < 0.05 as statistically significant. The mean concentration of FOXP3 was higher in serum samples from CC cases compared with CIN cases and controls, and this difference was statistically significant (P value < 0.001). More than half (52/90,58 %) of serum samples from CC cases had FOXP3 concentrations greater than 0.0545 ng/ml (P value < 0.001). Increase serum FOXP3 expression was not associated with CIN. Increase in serum FOXP3 concentrations were observed to increase the chances of CC by 2 times (OR: 2.094, P value 0.038, 95 % CI: 1.042---4.209). Serum FOXP3 is likely associated with cervical lesions especially CC in our study population. Serum FOXP3 testing may be useful in resource limited settings to aid detection of such lesions given the challenges associated with cytology and VIA. We recommend diagnostic utility studies for circulating FOXP3 as a biomarker for detection of cervical cancer.

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BACKGROUND: This study aimed to investigate whether persistent human papillomavirus integration at the same loci (PHISL) before and after treatment can predict recurrent/residual disease in women with CIN2-3. METHODS: A total of 151 CIN2-3 women treated with conization between August 2020 and September 2021 were included. To investigate the precision of HPV integration, we further analyzed HPV integration-positive patients. Sensitivity, specificity, positive and negative predictive values (PPV and NPV, respectively), and the Youden index for predicting recurrence/residual disease were calculated. RESULTS: Among the 151 enrolled CIN2-3 women, 56 were HPV integration-positive and 95 had HPV integration-negative results. Six (10.7%) experienced recurrence among 56 HPV integration-positive patients, which was more than those in HPV integration-negative patients (one patient, 1.1%). In the 56 HPV integration-positive patients, 12 had positive HPV results after treatment, seven had PHISL, and two had positive cone margin. Among the seven patients who tested with PHISL, six (85.7%) had residual/recurrent disease. PHISL was a prominent predictor of persistent/recurrent disease. The HPV test, the HPV integration test, and PHISL all had a sensitivity of 100% and a NPV of 100% for residual/recurrent disease. PHISL showed better specificity (98.0% vs. 82.0%, p = 0.005) and PPV (85.7% vs. 40.0%, p = 0.001) than the HPV test for predicting recurrence. CONCLUSIONS: The HPV-integration-positive CIN2-3 women had much higher relapse rates than HPV-integration-negative CIN2-3 women. The findings indicate that PHISL derived from preoperative and postoperative HPV integration tests may be a precise biomarker for the identification of residual/recurrent CIN 2/3.

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OBJECTIVE: This systematic review and meta-analysis aimed to compare the risk of recurrence and cancer progression after surgical treatment for oral potentially malignant disorders (OPMD) and precancerous lesions in different anatomical sites. MATERIALS AND METHODS: A comprehensive search was conducted in nine databases and grey literature. We included randomized controlled trials assessing surgical treatment efficacy for OPMD and precancerous lesions of cervical, vaginal, anal, and penile sites. Excision or ablation surgical treatments were considered. RESULTS: Overall, 12 studies met the eligibility criteria for oral leukoplakia (OL), proliferative verrucous leukoplakia, cervical intraepithelial neoplasia (CIN), vaginal intraepithelial neoplasia, and anal intraepithelial neoplasia (AIN). In qualitative analysis of surgical protocols, the lack of margin description impacts the clinical outcomes of OL and AIN, and the ablative protocols were heterogeneous in both OPMD and precancerous lesions. No significant difference in OL (risk ratio 0.82 [95% CI: 0.59-1.15]) and CIN (risk ratio 0.31 [95% CI: 0.09-1.09]) for recurrence was observed when cold-knife was compared with ablative protocols. OL exhibited higher recurrence and cancer progression rates compared to CIN and AIN. CONCLUSION: There is no difference in recurrence risk post-surgical treatment for OL and CIN. Surgical protocols for oral leukoplakia and CIN/AIN lack standardized approaches.

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Background/Objectives: To investigate the risk factors for CIN2+ lesions (cervical intraepithelial neoplasia 3 or worse) in endocervical curettage (ECC) and to evaluate the relationship between the addition of ECC to punch biopsy in terms of the yield of CIN2+ lesions. Methods: Between February 2018 and 2019, data on colposcopy results from 11,944 patients were gathered from the Cancer Department of the Turkish Ministry of Health across the country. A total of 6370 women whom were referred to colposcopy were included in this study. Risk factors were identified using both univariate and multivariate logistic analyses. Results: The median age was 42 years old (range, 30-65). ASC-H (atypical squamous cells-suggestive of high-grade squamous intraepithelial lesion)/HSIL (high-grade intraepithelial lesion) cytology (OR 7.648 95% CI (3.933-14.871)) and HPV (human papillomavirus)-16/18 infection (OR 2.541 95% CI (1.788-3.611)) were identified as risk factors for having CIN2+ lesions. CIN2+ diagnostic yield by ECC is only 1.2% all patients. CIN2+ diagnostic yield by punch biopsy and ECC are 9.7% and 6% of patients, respectively. A higher CIN2+ yield by ECC was observed with increasing age. Among cytology groups, ASC-H/HSIL has highest CIN2+ yield by ECC. Finally, in patients with incomplete visualization of the squamocolumnar junction (SCJ), ECC yields approximately twice as many CIN2+ lesions. Conclusions: ECC should be considered in cases of advanced patient age and in situations where the SCJ is not routinely visualized. In addition, evaluation of the endocervical canal is necessary in HPV-positive cases infected with HPV-16/18 types and in cases infected with HPV of any type but with cytological abnormalities.

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The risk associated with single and multiple human papillomavirus (HPV) infections in cervical intraepithelial neoplasia (CIN) remains uncertain. This study aims to explore the distribution and diagnostic significance of the number of high-risk HPV (hr-HPV) infections in detecting CIN, addressing a crucial gap in our understanding. This comprehensive multicenter, retrospective study meticulously analyzed the distribution of single and multiple hr-HPV, the risk of CIN2+, the relationship with CIN, and the impact on the diagnostic performance of colposcopy using demographic information, clinical histories, and tissue samples. The composition of a single infection was predominantly HPV16, 52, 58, 18, and 51, while HPV16 and 33 were identified as the primary causes of CIN2+. The primary instances of dual infection were mainly observed in combinations such as HPV16/18, HPV16/52, and HPV16/58, while HPV16/33 was identified as the primary cause of CIN2+. The incidence of hr-HPV infections shows a dose-response relationship with the risk of CIN (p for trend <0.001). Compared to single hr-HPV, multiple hr-HPV infections were associated with increased risks of CIN1 (1.44, 95% confidence interval [CI]: 1.20-1.72), CIN2 (1.70, 95% CI: 1.38-2.09), and CIN3 (1.08, 95% CI: 0.86-1.37). The colposcopy-based specificity of single hr-HPV (93.4, 95% CI: 92.4-94.4) and multiple hr-HPV (92.9, 95% CI: 90.8-94.6) was significantly lower than negative (97.9, 95% CI: 97.0-98.5) in detecting high-grade squamous intraepithelial lesion or worse (HSIL+). However, the sensitivity of single hr-HPV (73.5, 95% CI: 70.8-76.0) and multiple hr-HPV (71.8, 95% CI: 67.0-76.2) was higher than negative (62.0, 95% CI: 51.0-71.9) in detecting HSIL+. We found that multiple hr-HPV infections increase the risk of developing CIN lesions compared to a single infection. Colposcopy for HSIL+ detection showed high sensitivity and low specificity for hr-HPV infection. Apart from HPV16, this study also found that HPV33 is a major pathogenic genotype.

Asunto(s)

Infecciones por Papillomavirus , Displasia del Cuello del Útero , Neoplasias del Cuello Uterino , Humanos , Femenino , Estudios Retrospectivos , Infecciones por Papillomavirus/diagnóstico , Infecciones por Papillomavirus/virología , Infecciones por Papillomavirus/epidemiología , Infecciones por Papillomavirus/complicaciones , China/epidemiología , Displasia del Cuello del Útero/virología , Displasia del Cuello del Útero/diagnóstico , Displasia del Cuello del Útero/epidemiología , Adulto , Persona de Mediana Edad , Adulto Joven , Neoplasias del Cuello Uterino/virología , Neoplasias del Cuello Uterino/diagnóstico , Neoplasias del Cuello Uterino/epidemiología , Colposcopía , Coinfección/virología , Coinfección/epidemiología , Papillomaviridae/genética , Papillomaviridae/aislamiento & purificación , Papillomaviridae/clasificación , Anciano , Genotipo , Incidencia

RESUMEN

Background: Altered lipid levels may be associated with the development of a number of malignancies, including cancer of the cervix. However, there is limited understanding of this relationship in the rural Ugandan context. Objective: We investigated the connection between dyslipidaemias and cervical intraepithelial neoplasia (CIN) among women attending the cervical cancer clinic at Mbarara Regional Referral Hospital in south-western Uganda. Methods: This unmatched case-control study was conducted between December 2022 and February 2023 and included women with CIN (cases) and women without intraepithelial lesions (controls) in a 1:1 ratio. Participants were selected based on cytology and/or histology results, and after obtaining written informed consent. Demographic data were collected, and venous blood was drawn for lipid profile analysis. Dyslipidaemia was defined as: total cholesterol > 200 mg/dL, low-density lipoprotein > 160 mg/dL, triglycerides > 150 mg/dL, or high-density lipoprotein < 40 mg/dL. At diagnosis, cases were categorised as either CIN1 (low grade) or CIN2+ (high grade). Results: Among the 93 cases, 81 had CIN1, while 12 had CIN2+. Controls had a 13.9% (13/93) prevalence of high triglycerides and cases had a prevalence of 3.2% (3/93; p = 0.016). Reduced high-density lipoprotein was the most prevalent dyslipidaemia among cases (40.9%; 38/93). Statistically significant associations were found between high serum triglycerides and CIN (odds ratio: 1.395, 95% confidence interval: 0.084-1.851, p = 0.007). Conclusion: A notable association was observed between triglyceride dyslipidemia and CIN. Further studies into biochemical processes and interactions between lipids and cervical carcinogenesis are recommended through prospective cohort studies. What this study adds: This research provides additional information on the potential role of lipids in cervical carcinogenesis among women in rural Uganda. It also presents the possible prevalence of multimorbidity involving cervical cancer and cardiovascular diseases, particularly in low-resource settings lacking preventive measures against the increasing prevalence of dyslipidaemia.