Search Results (185)

Background/Objectives: This study evaluated the real-world effectiveness of prophylactic Human Papillomavirus (HPV) vaccination in Korean women aged over 26 years, focusing on its impact on persistent HPV infection and disease progression. Methods: This multicenter prospective study analyzed data from the Korea HPV Cohort (2010–2021). After applying exclusion criteria, the final analytical cohort included 1,231 women aged ≥ 27 years with cytologic findings of atypical squamous cells of undetermined significance/low-grade squamous intraepithelial lesions and HPV infection. Propensity score matching was used to compare vaccinated (n = 340) and unvaccinated (n = 891) participants. After matching, 273 vaccinated and 273 unvaccinated individuals were included in the final analysis. The primary outcomes were persistent HPV infection and progression to biopsy-confirmed cervical intraepithelial neoplasia grade 2 or worse (CIN2+). Logistic and Cox regression models were employed, with additional age-stratified analyses. Results: Among women aged 27–39 years, vaccination was significantly associated with a 54% reduction in the odds of persistent HPV infection (odds ratio = 0.46; 95% CI: 0.22–0.96; p = 0.040). In the full cohort, vaccinated participants had a 62% lower risk of progression to CIN2+ compared with unvaccinated participants (hazard ratio = 0.38; 95% CI: 0.18–0.81; p = 0.011). Body mass index had a notable impact on HPV persistence in HPV 16/18 genotype groups. Conclusions: HPV vaccination effectively reduced persistent infection and progression to CIN2+ in Korean women, particularly those vaccinated before age 40. These findings support the age-extended HPV vaccination policies in South Korea. Full article

Vulvar carcinoma is the fourth most common gynecological cancer, with squamous cell carcinoma being the most frequent type. Vulvar intraepithelial neoplasia (VIN) is a precursor lesion and is strongly associated with human papillomavirus (HPV) infection. This paper presents two patients in their sixth decade of life, the first diagnosed with VIN 3 (carcinoma in situ) and the second with stage IA keratinizing squamous cell carcinoma. Both patients had HPV infection; immunohistochemistry confirmed HPV-dependent VIN3 in the first case, while the second patient had a pre-existing HPV high-risk 53 infection. Both patients underwent partial vulvectomy, with the second also having bilateral inguinal–femoral lymph node dissection, which showed no lymph node invasion. The first patient had a histopathological result of VIN 3 with clear margins. The second patient underwent adjuvant radiotherapy following restaging pathology. Both are showing favorable postoperative progress. Conclusions. The early diagnosis of vulvar neoplasms enables less radical but effective surgeries, balancing oncologic control with quality of life. A multidisciplinary approach is essential for adjusting treatments, improving both clinical outcomes and patient well-being. Full article

Penile intraepithelial neoplasia (PeIN) is a rare but clinically significant condition that can progress to invasive squamous carcinoma. Early diagnosis is crucial but often challenging due to its heterogeneous clinical and dermoscopic presentation, which can mimic other benign or malignant lesions. In this study, we report two cases of pigmented penile lesions evaluated using non-invasive imaging techniques: reflectance confocal microscopy (RCM) and line-field confocal optical coherence tomography (LC-OCT). Both methods revealed characteristic features such as hyperkeratosis, parakeratosis, acanthosis, nuclear pleomorphism of keratinocytes, and the presence of bright intraepithelial dendritic cells, correlating closely with histopathological findings of high-grade basaloid PeIN. Our findings highlight the valuable role of RCM and LC-OCT in improving the differential diagnosis of genital lesions, potentially reducing the need for invasive diagnostic procedures and ensuring early, appropriate management. Full article

Background: Opportunistic screening is one major screening approach for esophageal squamous cell carcinoma (ESCC). We aimed to develop a score-based risk stratification model to assess the risk of ESCC and precancerous lesions in opportunistic screening and to validate it in an external population. Methods: The study was a secondary analysis of a published esophageal cancer screening trial. The trial was conducted in 39 secondary or tertiary hospitals in China, with 14,597 individuals including 71 high-grade intraepithelial neoplasia (HGIN) and 182 ESCC, enrolled for opportunistic screening. Additionally, questionnaires and endoscopy were performed. The primary outcome was histology-confirmed high-grade esophageal lesions, including HGIN and ESCC. The predictors were selected using univariable and multivariable logistic regression. Model performance was primarily measured with the area under the receiver operating characteristic curve (AUROC). Results: The score-based prediction model contained 8 variables on a 21-point scale. The model demonstrated an AUROC of 0.833 (95% CI, 0.803–0.862) and 0.828 (95% CI, 0.793–0.864) for detecting high-grade lesions in the training and validation cohorts, respectively. Using the cut-off score determined in the training cohort (≥9), the sensitivity reached 70.0% (95% CI, 50.6–85.3%), 81.3% (95% CI, 63.6–92.8%), and 81.1% (95% CI, 64.9–92.0%) in the validation cohort for detecting HGIN, early ESCC, and advanced ESCC, respectively, at a specificity of 76.4% (95%CI, 75.4–77.4%). The score-based model exhibited satisfactory calibration in the calibration plots. The model could result in 75.6% fewer individuals subjected to endoscopy. Conclusions: This score-based model demonstrated superior discrimination for esophageal high-grade lesions. It has the potential to inform referral decisions in an opportunistic screening setting. Full article

Background/Objectives: Understanding the regional distribution of human papillomavirus (HPV) genotypes is essential for guiding effective vaccination and screening strategies. This study aimed to assess the prevalence and distribution of HPV genotypes among unvaccinated women aged 30 years and older undergoing routine screening in Ankara. It also aimed to compare the frequencies of genotypes included and not included in current vaccines and to investigate their association with cervical smear cytology. Methods: This descriptive, cross-sectional, single-center study was conducted at Ankara Etlik City Hospital between 15 November 2024 and 15 February 2025. A total of 500 sexually active, unvaccinated women aged 30 years or older were enrolled. Cervical swab samples were analyzed for HPV DNA and genotypes using real-time PCR (28-type panel), and cytology results were retrospectively obtained from medical records. Results: HPV infection was detected in 18.2% of participants. Among HPV-positive women, 71.4% had single-type and 28.6% had multiple-type infections. The most common high-risk genotypes among HPV-positive individuals were HPV 16 (13.2%), HPV 18 (13.2%), and HPV 59 (13.2%). While 35.2% of HPV-positive cases included genotypes covered by the nonavalent vaccine, 64.8% involved at least one genotype not covered, mainly HPV 59, 44, and 51. HPV was detected in 17% of individuals with normal cytology, 19% of those with atypical squamous cells of undetermined significance (ASC-US), and 100% of cases with low-grade squamous intraepithelial lesion (LSIL) (p < 0.001). Conclusions: The findings emphasize the persistence of high-risk and non-vaccine-covered HPV types in the population, highlighting the need for updated vaccination policies and the development of broader-spectrum vaccines aligned with local genotype profiles. Full article

The aberrant DNA methylation of tumour suppressor genes, including CADM1, MAL, and PAX1, is implicated in cervical carcinogenesis. Objectives: This pilot study aimed to evaluate the methylation levels of these genes in HPV-positive women and assess their diagnostic performance for detecting histologic high-grade squamous intraepithelial lesions (HSILs) and carcinoma. Methods: Cervical samples from 73 HPV-positive women were analyzed using droplet digital PCR (ddPCR) to quantify methylation levels of CADM1, MAL, and PAX1. The methylation levels were further compared across cytological and histological classifications. A control group of 26 HPV-negative women with negative cytology was also included. The diagnostic performance was assessed through receiver operating characteristic (ROC) analysis, as well as sensitivity and specificity calculations for individual genes and gene panels. Results: MAL methylation was absent in NILM, LSIL, and HSIL samples but was significantly elevated in carcinoma. PAX1 methylation was observed in both high-grade and some low-grade lesions. CADM1 methylation remained low or undetectable in the NILM, LSIL, and HSIL groups, with a significant increase observed in carcinoma cases. The CADM1/MAL panel demonstrated the highest diagnostic accuracy, with an area under the curve (AUC) of 0.912, 70% sensitivity, and 100% specificity. ddPCR exhibited superior analytical sensitivity compared to real-time PCR. Conclusions: The CADM1/MAL methylation panel, assessed by ddPCR, may serve as a specific biomarker for the triage of HPV-positive women at risk of HSIL and carcinoma. However, this study’s limited sample size and single-centre design necessitate cautious interpretation. Further validation in larger, population-based cohorts is necessary to confirm its clinical utility. Full article

Introduction: Anal squamous cell carcinoma (ASCC) is a rare but increasingly common gastrointestinal malignancy, mainly associated with oncogenic human papillomaviruses (HPVs). The role of non-coding RNAs (ncRNAs) in tumorigenesis is recognized, but the impact of viral ncRNAs on host gene expression remains unclear. Methods: We re-analyzed total RNA-Seq data from 70 anal biopsies: 31 low-grade squamous intraepithelial lesions (LGSIL), 16 high-grade SIL (HGSIL), and 23 ASCC cases. Microbial composition was assessed taxonomically. Novel viral miRNAs were predicted using vsRNAfinder and linked to host targets using TargetScan and expression correlation analyses. Results: Microbial profiling revealed significant differences in abundance, with Alphapapillomaviruses types 9, 10, and 14 enriched across lesion grades. We identified 90 novel viral miRNAs and 177 significant anti-correlated miRNA–mRNA interactions. Target genes were enriched in pathways related to cell cycle, epithelial–mesenchymal transition, lipid metabolism, immune modulation, and viral replication. Discussion: Our findings suggest that HPV-derived miRNAs, including those from low-risk types, may contribute to neoplastic transformation by modulating host regulatory networks. Conclusion: This study highlights viral miRNAs as potential drivers of HPV-related anal cancer and supports their utility as early biomarkers and therapeutic targets in ASCC. Full article

Background: Cervical dysplasia is a pre-malignant condition of the uterine cervix and is highly prevalent in Sub-Saharan Africa; especially affecting HIV-infected Black women. The anti-dysplastic effect of vitamin D hormones in cervical dysplasia is poorly understood. Therefore, we conducted a cross-sectional case–control observational study to assess the relationship between serum 25-hydroxycholecalciferol (25(OH)D) and cervical dysplasia, amongst Black women with and without HIV infection. Methods: The study participants attended a gynaecologic oncology clinic at an academic hospital in Pretoria, South Africa (n = 109). Patient clinical data were obtained during consultation. Cervical dysplasia was identified by cytology (PAP smear) which classified the case group as high-grade squamous epithelial lesions (HSILs), and the control group as <HSIL. Serum biochemistry measured 25(OH)D and its covariate biochemical variables. The data were statistically modelled to adjust for clinical and biochemical covariates, identify a significant relationship (p ≤ 0.05) between 25(OH)D and cervical dysplasia, and analyse subgroup interaction between HIV status and cervical dysplasia. Results: The data showed high levels of vitamin D insufficiency and deficiency in Black women with and without HIV infection. After covariate adjustment, 25(OH)D demonstrated an inverse relationship with HSIL in HIV-uninfected Black women. Furthermore, an interaction effect between women with and without HIV infection was observed. Conclusions: The role of 25(OH)D in the primary prevention of cervical dysplasia in Black women without HIV infection is promising, and dosing strategies require investigation. Also, future studies exploring the immunomodulatory role of 25(OH)D in cervical dysplasia in HIV-infected women is warranted. Full article

Cervical intraepithelial neoplasia (CIN) is caused by human papillomavirus (HPV); however, factors such as HPV genotype and individual immune response may also contribute to its development. The loop electrosurgical excision procedure (LEEP) is a treatment for high-grade cervical intraepithelial neoplasia (CIN), as approximately 30% of these cases may progress to cancer. However, 20–40% of cases will regress spontaneously. HPV16 infection constitutes the highest risk for progression to cervical cancer and a lower probability of regression. Knowledge regarding the regression of lesions caused by other high-risk genotypes alone or in association with biomarker expression and lesion length has been limited. In the present study, the regression rates of high-grade squamous intraepithelial lesions were calculated. Twenty-one percent of the 161 women diagnosed with CIN2-3 on colposcopy-directed biopsies exhibited regression (defined as CIN1 or less) in the subsequent cone excisions. The mean interval between biopsy and treatment was 113 days (range of 71–171). High-grade lesions of the squamous epithelium caused by HPV16, together with lesions caused by HPV31, 52 and 58, showed significantly lower regression rates (HR 0.54, 0.22–0.75; low-regression group) than lesions caused by HPV18, 33, 35, 39, and 45 (HR 2.85, 1.54–5.28; high-regression group). A multivariate analysis of HPV genotypes, epithelial expressions of pRb and p53, immune cell proportions in the stroma (CD4/CD25 and CD4/CD8), and lesion lengths correctly predicted regression in 78% (Harrell’s C). A Harrell’s C value of 82% for the low-regression group indicates that different HPV genotypes or groups, together with divergent patterns of tumor suppressors, immune cells, and lesion size, can give prognostic information regarding the outcome of CIN2-3. Full article

Background/Objectives: Cervical cancer (CC) is a significant global health challenge, particularly in low- and middle-income countries (LMICs), where limited access to human papillomavirus (HPV) vaccination and effective CC screening results in a majority of cases and fatalities among women. Moreover, existing vaccines do not target HPV-independent cancers. Current screening methods are expensive and time-consuming, with a limited emphasis on CC protein biomarkers. Therefore, we aimed to validate critical markers that allow the development of affordable point-of-care screening tests for resource-limited settings. Methods: This study first optimized a cell lysis and protein extraction protocol for CC cell lines and clinical cervical swabs. Subsequently, four proteins—topoisomerase II alpha (TOP2A), minichromosome maintenance complex component 2 (MCM2), valosin-containing protein (VCP), and cyclin-dependent kinase inhibitor 2A (p16INK4a)—were quantified in the resulting lysates using enzyme-linked immunosorbent assays, as well as in cervical tumors and squamous intraepithelial lesions (SILs) using immunohistochemistry for further validation. Results: Acetone precipitation allowed for efficient cell isolation, and radioimmunoprecipitation assay buffer yielded the highest protein recovery. VCP and p16INK4a were overexpressed across all cancer cell lines compared to primary cells. All four biomarkers were overexpressed in high-grade SIL (HSIL) swab specimens and tumor samples, including CC subtypes, G1–G3 tumor grades, and HSILs. Lastly, we showed that the proteins could accurately classify swabs and tissue specimens into clinically relevant groups. Conclusions: The quantitative analysis of these biomarkers, along with the subsequent sensitive and specific clinical classification, highlights their potential application in SIL early detection and CC prevention, particularly in LMICs. Full article

Background/Objectives: Molecular triage strategies for cervical lesions based on miR-124-2 and FAM19A4 are poorly studied in various populations. The aim of this prospective study was to evaluate the individual and combined predictive performance of these two markers for the prediction of various histological categories of cervical lesions. Methods: An FAM19A4 and miR124-2 methylation analysis was performed on 70 samples from patients negative for intraepithelial lesion or malignancy (NILM), cervical intraepithelial neoplasia (CIN)1-3 and squamous cervical carcinoma (SCC), along with human papillomavirus (HPV) genotyping and cytological and histopathological assessment. Descriptive statistics examined clinical associations, while sensitivity analysis evaluated the predictive performance of these markers individually and combined. Results: The sensitivity of miR-124-2 was 28.1%, while its specificity was 86.8% for SCC. The ROC values ranged between 0.25 and 0.62 for the evaluated histological categories, suggesting a poor to moderate predictive performance. FAM19A4 had a sensitivity of 36% for predicting CIN3 and SCC, as well as a high specificity for CIN3 and SCC (88.9%), with ROC values between 0.35 and 0.73 for the evaluated histological categories. The combined tests improved the PPV for higher-risk lesions (CIN3, SCC), but did not significantly improve the ROC values. FAM19A4 achieved the best performance for the prediction of CIN2+ (ROC: 0.64) and CIN3+ lesions (ROC: 0.73). Conclusions: We hypothesize that while not suitable as stand-alone diagnostic tools, such biomarkers may aid in stratifying patients and optimizing referral decisions, pending further validation in larger, population-based cohorts. Full article

Background/Objectives: This study evaluates the diagnostic performance of DNA methylation testing, alone and in combination with cervical cytology, for high-grade squamous intraepithelial lesion (HSIL) detection. Methods: A prospective study was conducted on 170 high-risk HPV (hr-HPV)-positive women. DNA methylation (QIAsure^®) and cervical cytology were performed prior to cervical large loop excision of the transformation zone (LLETZ). Sensitivity, specificity, and area under the curve (AUC) metrics were calculated, including stratified analyses for HPV16/18 and other hr-HPV genotypes. Results: DNA methylation alone achieved a sensitivity of 69.7%, specificity of 79%, and an AUC of 0.796 for HSIL detection. The combination of cervical cytology and DNA methylation improved sensitivity to 94.7%, specificity to 76.3%, and AUC to 0.860. Stratification by HPV genotype revealed that in HPV16/18-positive cases, DNA methylation alone reached an AUC of 0.790, while the combination with cytology significantly enhanced performance to 0.917. DNA methylation alone demonstrated an AUC of 0.744 for other hr-HPV types, and the combined approach achieved an AUC of 0.849. Specificity for the combined approach was notably higher in HPV16/18-positive women (88.9%) than in other hr-HPV cases (72.4%), whereas the sensitivity of the combined approach was significantly higher in both groups (94.5% vs. 95%, respectively). Conclusions: The integration of DNA methylation with cervical cytology significantly enhances diagnostic accuracy for CIN2+ lesions, especially in HPV16/18-positive cases. However, the comparatively lower AUC and specificity observed in other hrHPV types suggest the need for further optimization to enhance accuracy in non-16/18 infections. These findings support the integration of methylation-based testing with cytology as a valuable triage strategy for improving cervical cancer screening and patient management. Full article

Background and Objectives: The relationship between the vaginal microbiota, human papillomavirus infection (HPV), and cervical precancerous lesions is a critical area of research, as it influences both the progression of HPV-related diseases and potential treatment strategies. New evidence suggests that Lactobacillus crispatus dominance in the microbiota may protect against HPV persistence and speed the elimination of HPV. This study aims to explore the relationship between the vaginal microbiota composition and HPV infection, focusing on the impact of these factors on the development of cervical precancerous lesions. Materials and Methods: A comprehensive literature review was conducted using the PubMed database, focusing on studies that analyzed the association between the vaginal microbiota and HPV infection in the context of cervical dysplasia. This study was primarily based on clinical data on HPV integration in women with low-grade squamous intraepithelial lesions (LSILs), high-grade squamous intraepithelial lesions (HSILs), and cervical cancer. Results: Different types of vaginal microbiota communities (CSTs) have different pathogenic or protective potential. Healthy women predominantly exhibited CST I, with Lactobacillus crispatus as the dominant microorganism. CST IV, associated with increased anaerobic bacteria, was most common in HSIL and cervical cancer patients. Statistical analysis revealed that bacterial vaginosis (BV) was significantly associated with HPV persistence, with studies reporting a 1.8–3.4-fold increased risk (p < 0.05) of persistent HR-HPV infection in BV-positive women. Conclusions: Our literature review suggests that the composition of the vaginal microbiota can modulate the local immune response, the expression of viral oncogenes, and the integrity of the epithelial barrier. Furthermore, certain bacterial genes or metabolic pathways can be associated with a favorable or unfavorable outcome of the disease. Analysis of the vaginal microbiota could serve as an additional risk assessment tool, helping to distinguish between regressing and progressive precancerous conditions. Full article

Persistent high-risk Human Papillomavirus infection is the primary factor in cervical carcinogenesis. However, other host-related features are believed to play a role as well. Recent research suggests that the vaginal microbiome and the immune microenvironment play a significant role in the acquisition and persistence of Human Papillomavirus infection, as well as in the regression or progression of cervical intraepithelial lesions. Studies in this emerging field describe factors associated with this interaction, though the precise nature remains incompletely understood. In this narrative review, we aim to summarize the current literature on the topic and propose hypotheses and recommendations for future research and treatment strategies. Full article

Background: Cervical cancer is one of the most common cancers in women worldwide, with the leading risk factor being high-risk human papillomavirus (HR-HPV); persistent HR-HPV infection leads to cervical dysplasia. With early screening and, if indicated, therapeutic strategies such as a loop electrosurgical excision procedure (LEEP) and large loop excision of the transformation zone (LLETZ), morbidity and mortality in this population are decreasing. However, it is suspected that these procedures may have an impact on sexual dysfunction. Methods: In this single-center prospective longitudinal study, we recruited patients with a high-grade squamous intraepithelial lesion (HSIL) and HR-HPV-positive result and evaluated the impact of LEEP/LLETZ on their sexual life and psychological well-being. All participants received two questionnaires—the Female Sexual Function Index (FSFI) and the Brief Index of Sexual Function-Women (BISF-W)—after diagnosis, before treatment, and three months after the procedure. Results: A total of 40 women aged 28 to 55 years were enrolled. This study showed no significant changes in both the FSFI (F(1,39) = 0.774; p = 0.38) and BISF-W total scores (F(1,39). This study revealed that 32/40 (80%) of participants based on the FSFI either exhibited no change or improved sexual function. Only 3/40 (7.5%) mentioned sexual dysfunction after procedures. This study also found that the mean score for sexual function based on the FSFI was 2.80; p = 0.102. Conclusions: These findings suggest that patients who qualified for LEEP/LLETZ can be reassured that the anxiety they experience prior to treatment is not necessarily justified. This provides evidence of the safety of loop excision procedures in terms of sexual functioning after the procedure. Nevertheless, further studies are needed to analyze the potential risk factors that may contribute to adverse sexual outcomes and to achieve a better understanding of this complex problem. Full article