Search Results (99)

Background: Vaginal intraepithelial neoplasia (VaIN) is a rare but potentially precancerous condition strongly associated with human papillomavirus (HPV) infection. Despite increased detection rates due to HPV screening and colposcopy, diagnosis and management remain challenging. This study aimed to evaluate the epidemiological characteristics, risk factors, and outcomes of VaIN in patients referred to a tertiary academic center. Methods: We conducted a retrospective analysis of 48 patients who underwent colposcopy-directed vaginal biopsies between January 2019 and June 2024 at the Medical University of Warsaw. Data collected included patient demographics, HPV status, cytology, histopathology, and treatment outcomes. Patients were grouped based on the presence and grade of VaIN (VaIN 1 vs. VaIN 2/3). Statistical analyses were performed using SPSS software. Results: VaIN was diagnosed in 24 patients (50%), VaIN was confirmed in half of the cohort, VaIN 2 in 30%, and VaIN 3 in 18% of cases. HPV infection and prior cervical pathology were significantly associated with VaIN diagnosis (P = 0.03 and P = 0.05, respectively), and high-risk HPV infection correlated with higher-grade lesions (P = 0.04). Among VaIN 2+ cases, most patients required laser ablation or surgical excision, while VaIN 1 often regressed spontaneously. Regression occurred in 11 cases, and high-risk HPV infection was inversely associated with spontaneous regression (P = 0.04). Conclusions: This study confirms the central role of HPV, particularly high-risk subtypes, in VaIN pathogenesis. Conservative management may be appropriate for VaIN 1, while VaIN 2+ requires active intervention. HPV genotyping should be integrated into diagnostic workups, and long-term follow-up is essential due to the risks of persistence and recurrence. Full article

Human papillomavirus 18 (HPV18) is the second most oncogenic high-risk HPV genotype, after HPV16, and is responsible for about 15% of cervical cancer cases worldwide. The integration of high-risk HPV DNA into the host genome leads to the disruption of the E1 and/or E2 genes, which is considered a risk factor for viral-induced carcinogenesis. This study examined the disruption events of HPV18 E1 and E2 genes in precancerous cervical lesions to investigate the rates and sites of gene disruption in the Greek population. The complete E1 and E2 genes were amplified using three and four overlapping primer sets, respectively. Extensive analysis revealed that the disruption/deletion events of the E1 and E2 genes were detected in all grades of cytology-determined lesions, with high frequency. E2 gene disruption was significantly related to LSIL+ cases (Fisher’s exact test, p = 0.022). No significant association was found in the analysis of the E1 gene. Additionally, no preferential sites of E1/E2 gene disruption were detected. This is the first study to provide evidence of disruption events of the HPV18 E1 gene. The data from the current analysis suggest that disruption of the E2 gene could be a significant marker for the progression of cytology-determined cervical dysplasia. However, future studies are required to evaluate whether different geographic populations have particular profiles regarding the rates and sites of gene disruption to further determine population-specific biomarkers. Full article

Background: Cervical cancer is a major global health concern, causing approximately 350,000 deaths annually. It is also preventable through effective prevention and early detection. To facilitate elimination, the World Health Organization (WHO) set targets for HPV vaccination, screening, and treatment. Achieving these goals requires frameworks to monitor screening program performance. As many regions transition to HPV primary screening, a standardized Cervical Cancer Screening Cascade can track performance, identify gaps in follow-up, and optimize resource allocation. Methods: This paper introduces a structured cascade developed to monitor uptake, retention, and outcomes in HPV-based screening programs. The Cascade was created through collaboration between public health experts, clinicians, and researchers at the University of British Columbia (UBC), the Women’s Health Research Institute, and BC Cancer. Results: The Cascade outlines four phases: screening, triage, detection, and treatment. Each phase includes two substages: “uptake” and “results,” with an additional substage in screening (“invitation”). “Screening” assesses invitation effectiveness and participation. “Triage” tracks follow-up after a positive screen. “Detection” evaluates attendance at diagnostic appointments, and “Treatment” measures the treatment rate for those with precancerous lesions. Conclusions: The Cascade can guide emerging and existing HPV screening programs within Canada and other similarly resourced settings and serve as a benchmark tool for programs to assess their progress towards cervical cancer elimination. Full article

Precision prevention strategies for cervical cancer that integrate genetic biomarkers provide opportunities for personalized risk assessment and optimized preventive measures. An HPV infection–Precancerous–Cancer risk assessment model incorporating genetic polymorphisms and DNA methylation was developed to better understand the regression and progression of cervical lesions by HPV infection status. Utilizing a virtual cohort of 300,000 Taiwanese women aged 30 years and older, our model simulated the natural history of cervical cancer, capturing transitions from a healthy state through precancerous lesions (LSILs and HSILs) to invasive carcinoma and incorporating the possibility of regression between states. Genetic and epigenetic markers significantly influenced disease transitions, demonstrating heterogeneous risks among women with distinct molecular biomarker profiles. Guided by these individual risk profiles, tailored preventive strategies including varying intervals for Pap smear screening, HPV DNA testing, and HPV vaccination showed improved efficiency and effectiveness in reducing cervical cancer incidence compared to uniform approaches. The proposed dynamic transition model of cervical neoplasms incorporating genetic biomarkers can facilitate the development of an individualized risk-based approach for guiding precision prevention towards the goal of cervical cancer elimination. Full article

Cervical cancer remains one of the main causes of female mortality, especially in middle- and low-income countries, despite efforts towards the implementation of global vaccination against human papillomavirus (HPV). The aim of this study was to review and compare the most recently published international guidelines providing recommendations on cervical cancer screening strategies among average and high-risk women. Thus, a comparative review of guidelines by the US Preventive Services Task Force (USPSTF), the American Cancer Society (ACS), the American Society of Clinical Oncology (ASCO), the World Health Organization (WHO), the Canadian Task Force on Preventive Health Care (CTFPHC), the Cancer Council Australia (CCA), and the European Guidelines (EG) was conducted. There is an overall agreement regarding the suggestions made for women younger than 21 and those older than 65, with all guidelines stating against routine screening, with the exceptions of CTFPHC and CCA that expand the age group to up to 70 and 75 years, respectively. Continuation of screening in older women is also suggested in those with a history of a precancerous lesion and those with inadequate screening. Most guidelines recommend routine screening at 30–65 years, while the WHO advises that screening should be prioritized at 30–49 years. HPV DNA testing is the method of choice recommended by most guidelines, followed by cytology as an alternative, except for CTFPHC, which refers to cytology only, with self-sampling being an acceptable method by most medical societies. Agreements exist regarding recommendations for specific groups, such as women with a history of total hysterectomy for benign reasons, women with a complete vaccination against HPV, individuals from the lesbian, gay, bisexual, transgender, and queer communities and women with multiple sexual partners or early initiation of sexual activity. On the other hand, the age group of 21–29 is addressed differently by the reviewed guidelines, while differentiations also occur in the screening strategies in cases of abnormal screening results, in women with immunodeficiency, those with in utero exposure to diethylstilbestrole and pregnant women. The development of consistent practice protocols for the most appropriate cervical cancer screening programs seems to be of major importance to reduce mortality rates and safely guide everyday clinical practice. Full article

Human papillomavirus (HPV) infection remains a principal cause of cervical cancer worldwide. Although large-scale vaccination efforts have substantially lowered HPV infection rates and precancerous lesions, not all regions have achieved high coverage. In Japan, proactive HPV vaccine recommendations were suspended from 2013 to 2022 due to concerns over alleged adverse events, causing vaccination rates to drop from over 70% to below 1%. This narrative review synthesized research published from 2014 to 2025 in PubMed, Cochrane Library, and Google Scholar, focusing on English-language studies. Inclusion criteria encompassed analyses of HPV vaccine efficacy or safety, policies related to vaccination in Japan or other countries, and investigations into vaccine hesitancy or media influences. Data were categorized into five thematic areas: historical and policy contexts, evidence of vaccine safety and efficacy, societal drivers of hesitancy, communication strategies, and administrative or clinical interventions. Evidence robustly confirms the HPV vaccine’s favorable safety profile, with severe adverse events appearing exceedingly rare. Nonetheless, media sensationalism and limited risk communication in Japan perpetuated mistrust, impeding vaccination uptake. Comparisons with Denmark and Ireland indicate that transparent, interactive risk communication can restore coverage to near-pre-suspension levels. Japan’s recent policy reforms, including reinstating proactive recommendations and catch-up initiatives, have begun to reverse vaccination hesitancy. Sustained policy support, evidence-based messaging, and empathetic engagement with communities are central to rebuilding trust in the HPV vaccine. Lessons from best international practices emphasize the importance of multifaceted interventions, collaborative stakeholder engagement, and transparent risk communication to reduce the burden of HPV-related malignancies. 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

Human papillomavirus (HPV) infection is a major risk factor for cervical cancer, demanding improved diagnostic strategies to distinguish between transient infections and those requiring intervention. Background: This systematic review and meta-analysis evaluated the diagnostic accuracy of HPV L1 immunocytochemistry (ICC) in detecting high-grade cervical intraepithelial neoplasia (CIN2+). Methods: We systematically analyzed data from 15 studies (PROSPERO 2022 CRD42022375916) comprising 3804 cervical smears with varying cytological findings (NILM to ≥ASC-US). Results: The pooled sensitivity for detecting CIN2+ was 80.7% (95% CI: 76.2–84.4%); however, substantial heterogeneity was present (I² = 65.97%, p < 0.001). Similarly, the pooled specificity was 56.9% (95% CI: 49.6–64%), with even higher heterogeneity (I² = 90.46%, p < 0.001). This considerable heterogeneity, which may be attributable to methodological variations or regional differences in HPV prevalence and genotyping, limits the generalizability of these findings. Furthermore, the moderate specificity suggests a high rate of false positives, limiting the clinical utility of HPV L1 ICC as a standalone diagnostic test. Conclusions: In conclusion, although HPV L1 ICC exhibits acceptable sensitivity for detecting CIN2+, its limitations, including low specificity and substantial heterogeneity, necessitate its use as an adjunct to other established diagnostic methods, alongside further research to enhance its diagnostic performance, and necessitate its use as a supplementary test alongside established diagnostic methods, pending further research to refine its clinical utility. 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

The role of vaginal dysbiosis in the progression of human papilloma virus (HPV) associated cervical lesions has gained attention in recent years. While many studies use 16S rRNA gene sequencing for microbiota analysis, shotgun metagenomic sequencing offers higher taxonomic resolution and insights into microbial gene functions and pathways. This systematic review evaluates the relationship between compositional and functional changes in the vaginal microbiome during HPV infection and cervical lesion progression. A literature search was performed according to PRISMA guidelines in PubMed, Web of Science, Scopus, and ScienceDirect databases. Seven studies utilizing metagenomic sequencing in patients with HPV infection or HPV-associated cervical lesions were included. Progression from HPV infection to cervical lesions and cancer was associated with a reduction in Lactobacillus species (particularly Lactobacillus crispatus) and an enrichment of anaerobic and pathogenic species, especially Gardnerella vaginalis. Heterogeneous enriched metabolic pathways were also identified, indicating functional shifts during lesion progression. As most studies were conducted in Asia, further research in diverse regions is needed to improve the generalizability of findings. Future studies employing metagenomic sequencing may help identify biomarkers for early pre-cancerous lesions and clarify the role of vaginal microbiota in persistent HPV infection and cervical dysplasia. Full article

The human microbiome plays a vital role in maintaining human homeostasis, acting as a key regulator of host immunity and defense mechanisms. However, dysbiotic microbial communities may cause disruption of the symbiotic relationship between the host and the local microbiota, leading to the pathogenesis of various diseases, including viral infections and cancers. One of the most common infectious agents causing cancer is the human papilloma virus (HPV), which accounts for more than 90% of cervical cancers. In most cases, the host immune system is activated and clears HPV, whereas in some cases, the infection persists and can lead to precancerous lesions. Over the last two decades, the advent of next-generation sequencing (NGS) technology and bioinformatics has allowed a thorough and in-depth analysis of the microbial composition in various anatomical niches, allowing researchers to unveil the interactions and the underlying mechanisms through which the human microbiota could affect HPV infection establishment, persistence, and progression. Accordingly, the present narrative review aims to shed light on our understanding of the role of the human microbiome in the context of HPV infection and its progression, mainly to cervical cancer. Furthermore, we explore the mechanisms by which the composition and balance of microbial communities exert potential pathogenic or protective effects, leading to either HPV persistence and disease outcomes or clearance. Special interest is given to how the microbiome can modulate host immunity to HPV infection. Lastly, we summarize the latest findings on the therapeutic efficacy of probiotics and prebiotics in preventing and/or treating HPV infections and the potential of vaginal microbiota transplantation while highlighting the significance of personalized medicine approaches emerging from NGS-based microbiome profiling and artificial intelligence (AI) for the optimal management of HPV-related diseases. Full article

Human papillomavirus (HPV) is a well-established etiological factor in the development of precancerous cervical lesions and cervical cancer. This narrative review synthesizes current evidence on the global prevalence, genotype distribution, and pathophysiological mechanisms of HPV infection, emphasizing regional epidemiological variations that influence prevention and treatment strategies. Particular attention is given to high-risk HPV genotypes, their role in carcinogenesis, and the impact of co-infections and the cervicovaginal microbiota on infection persistence and disease progression. Advances in diagnostic methodologies, including E6/E7 oncoprotein detection, DNA methylation, and microRNA-based assays, are examined in the context of improving screening accuracy and early detection. Furthermore, the review explores the psychological implications of HPV diagnosis and underscores the importance of integrating psychosocial support into clinical management. Given the challenges associated with screening coverage, the potential of self-sampling techniques, particularly in resource-limited settings, is discussed as a means to enhance accessibility and participation in cervical cancer prevention programs. By providing a comprehensive overview of these interrelated factors, this review highlights the necessity of a multidisciplinary approach that integrates novel diagnostic strategies, targeted prevention efforts, and supportive care to mitigate the burden of HPV-associated diseases. Full article

The objective of this study was to determine the relationship between the prevalence of high-risk human papillomavirus (HRHPV) and age in women with cervical neoplasia or cervical cancer. This retrospective study involved 470 women referred for abnormal cervical cytology between January 2021 and December 2023. The Cobas 4800 test was used to identify HRHPV genotypes; it specifically identified genotypes 16 and 18 and grouped the other high-risk genotypes into another category. The Cobas 4800 test was performed together with colposcopy and biopsies of cervical lesions. From the analysis, we selected 470 women who underwent cervical biopsies and HPV testing. Of them, 208 (44.3%) were HPV-negative. Among the 262 women positive for HPV, 13.0% were positive for genotype 16 only, 1.3% for genotype 18 only, and 35.1% for other HPV genotypes. HPV-16 was found in 58.3% of cases of cervical intraepithelial neoplasia grade 3 (CIN 3) in women under 35 years of age and in 20.9% of cases in women over 35 years of age. Furthermore, 51.9% of patients with cervical cancer tested positive for other high-risk HPV types, whereas 30.8% had HPV-16. Although other HPV genotypes were more frequent than HPV-16 and HPV-18 in individuals with cervical cancer, HPV-16 was the most common individual high-risk genotype in women ≥ 35 years of age with CIN-3. Full article

This study explores the effects of plant compounds on human papillomavirus (HPV)-induced W12 cervical precancer cells and bioelectric signaling. The aim is to identify effective phytochemicals, both individually and in combination, that can prevent and treat HPV infection and HPV associated cervical cancer. Phytochemicals were tested using growth inhibition, combination, gene expression, RT PCR, and molecular docking assays. W12 cells, derived from a cervical precancerous lesion, contain either episomal or integrated HPV16 DNA. Several compounds, including digoxin, tanshinone IIA, dihydromethysticin and carrageenan, as well as fractions of turmeric, ginger and pomegranate inhibited the growth of W12 precancer and cervical cancer cells. Curcumin and tanshinone IIA were the most active and relatively nontoxic compounds. RT-PCR analysis showed that tanshinone IIA activated the expression of p53, while repressing the expression of HPV16 E1, E2, E4, E6, and E7 viral transcripts in W12 (type 1 and 2) integrant cells. In addition, curcumin synergized with tanshinone IIA in HeLa cells. Molecular docking studies suggested tanshinone IIA and curcumin bind to the Na⁺/K⁺-ATPase ion channel, with curcumin binding with higher affinity. Our findings highlight the potential of these multifaceted phytochemicals to prevent and treat HPV-induced cervical cancer, offering a promising approach for combinatorial therapeutic intervention. Full article

Cervical cancer is one of the most prevalent cancers among women, posing a significant threat to their health. Early screening can detect cervical precancerous lesions in a timely manner, thereby enabling the prevention or treatment of the disease. The use of pathological image analysis technology to automatically interpret cells in pathological slices is a hot topic in digital medicine research, as it can reduce the substantial effort required from pathologists to identify cells and can improve diagnostic efficiency and accuracy. Therefore, we propose a cervical cell detection network based on collecting prior knowledge and correcting confusing labels, called PGCC-Net. Specifically, we utilize clinical prior knowledge to break down the detection task into multiple sub-tasks for cell grouping detection, aiming to more effectively learn the specific structure of cells. Subsequently, we merge region proposals from grouping detection to achieve refined detection. In addition, according to the Bethesda system, clinical definitions among various categories of abnormal cervical cells are complex, and their boundaries are ambiguous. Differences in assessment criteria among pathologists result in ambiguously labeled cells, which poses a significant challenge for deep learning networks. To address this issue, we perform a labels correction module with feature similarity by constructing feature centers for typical cells in each category. Then, cells that are easily confused are mapped with these feature centers in order to update cells’ annotations. Accurate cell labeling greatly aids the classification head of the detection network. We conducted experimental validation on a public dataset of 7410 images and a private dataset of 13,526 images. The results indicate that our model outperforms the state-of-the-art cervical cell detection methods. Full article