Search Results (642)

Background/Objectives: This study evaluated the in vitro probiotic potential of Lactiplantibacillus plantarum Probio87 (Probio87), focusing on its physiological robustness, safety, antimicrobial properties, and anticancer activity, with relevance to vaginal and cervical health. Methods: Tests included acid and bile salt tolerance, mucin adhesion, and carbohydrate utilization. Prebiotic preferences were assessed using FOS, GOS, and inulin. Antibiotic susceptibility was evaluated per EFSA standards. Antimicrobial activity of the cell-free supernatant (CFS) was tested against Staphylococcus aureus, Escherichia coli, and Candida species. Effects on Lactobacillus iners and L. crispatus were analyzed. Anticancer properties were assessed in HeLa, CaSki (HPV-positive), and C-33A (HPV-negative) cervical cancer cell lines through proliferation, apoptosis, angiogenesis, and cell cycle assays. Results: Probio87 showed strong acid and bile tolerance, efficient mucin adhesion, and broad carbohydrate utilization, favoring short-chain prebiotics like FOS and GOS over inulin. It met EFSA antibiotic safety standards. The CFS exhibited potent antimicrobial activity, including complete inhibition of Candida albicans. Probio87 selectively inhibited L. iners without affecting L. crispatus, indicating positive modulation of vaginal microbiota. In cervical cancer cells, the CFS significantly reduced proliferation and angiogenesis markers (p < 0.05), and induced apoptosis and cell cycle arrest in HPV-positive cells, with minimal effects on HPV-negative C-33A cells. Conclusions: Probio87 demonstrates strong probiotic potential, with safe, selective antimicrobial and anticancer effects. Its ability to modulate key microbial and cancer-related pathways supports its application in functional foods or therapeutic strategies for vaginal and cervical health. Full article

Cervical cancer remains a major health burden among women in sub-Saharan Africa, where screening is often limited. Persistent high-risk human papillomavirus (HR-HPV) infection is the principal cause, highlighting the need for accurate molecular diagnostics. This cross-sectional study evaluated the analytical performance of one mRNA assay, APTIMA^® HPV assay (APTIMA mRNA), and two DNA-based assays, the Abbott RealTime High Risk HPV assay (Abbott DNA) and Seegene Allplex™ II HPV28 assay (Seegene DNA), in 527 cervical samples from a South African tertiary hospital, focusing on 14 shared HR-HPV genotypes. Seegene DNA yielded the highest detection rate (53.7%), followed by Abbott DNA (48.2%) and APTIMA mRNA (45.2%). APTIMA mRNA showed a strong agreement with Abbott DNA (87.9%, κ = 0.80), 89.9% sensitivity, 91.2% NPV, and the highest accuracy (AUC = 0.8804 vs. 0.8681). The agreement between APTIMA mRNA and Seegene DNA was moderate (83.4%, κ = 0.70), reflecting target differences. Many DNA-positive/mRNA-negative cases likely represent transient infections, though some may be latent with reactivation potential, warranting a follow-up. In resource-constrained settings, prioritizing transcriptionally active infections through mRNA testing may enhance screening efficiency and reduce burden. Scalable, cost-effective assays with strong clinical utility are essential for broadening access and improving cervical cancer prevention. Further studies should assess the integration of mRNA testing into longitudinal screening algorithms. Full article

Introduction: Following up on treated high-grade cervical intraepithelial neoplasia (HSIL/CIN) lesions poses a challenge. Cervical cytology often has a high false-negative rate, while high-risk human papillomavirus (HR-HPV) DNA testing, though sensitive, lacks specificity. The detection of messenger RNA of the HR-HPV E6 and E7 oncoproteins (E6/E7 mRNA) is proposed as an indicator of viral integration, which is crucial for identifying severe lesions. Additionally, HPV vaccination could reduce recurrence rates in patients treated for high-grade cervical intraepithelial neoplasia. Objective: Our study aimed to assess the clinical utility of E6/E7 mRNA determination in the follow-up of HPV-immunized patients who were treated for HSIL/CIN. Methods: We conducted a retrospective observational study including 407 patients treated for HSIL/CIN. The recurrence rate and the validity parameters of E6/E7 mRNA testing were analyzed. Results: The recurrence rate for high-grade lesions was 1.7%. This low percentage might be related to the vaccination of patients who were not immunized before treatment. The sensitivity of the E6/E7 mRNA test was 88% at the first clinical visit, reaching 100% in the second and third reviews. Specificity was 91% at the first visit, 92% at the second, and 85% at the third. Regarding predictive values, the positive predictive value was 18% at the first visit, 10% at the second, and 14% at the third, while the negative predictive value was 100% across all follow-up visits. Conclusions: The E6/E7 mRNA test appears to be an effective tool for ruling out recurrence after treatment for HSIL/CIN lesions in HPV-immunized patients. Full article

Background: Effective triage of women testing positive for high-risk HPV DNA is essential to reduce unnecessary colposcopies while preserving cancer prevention. Cytology, the current standard, has limited specificity and reproducibility. The genotype-specific 7-type HPV E6/E7 mRNA test (PreTect HPV-Proofer’7), targeting HPV types 16, 18, 31, 33, 45, 52, and 58, detects transcriptionally active infections and may enhance risk stratification. Methods: Between 2019 and 2023, 34,721 women aged 25–69 underwent primary HPV DNA screening with the Cobas 4800 assay at the University Hospital of North Norway, within the national screening program. Of these, 1896 HPV DNA-positive women were triaged with liquid-based cytology with atypical squamous cells of undetermined significance or worse (≥ASC-US) and the 7-type HPV mRNA test. Histological outcomes were followed through October 2024. Diagnostic performance for CIN2+ was evaluated overall and by genotype. Results: CIN2+ prevalence was 13.3%. The mRNA test reduced test positivity from 50.3% to 33.4% while maintaining comparable sensitivity (70.6% vs. 72.2%) and improving specificity (72.3% vs. 53.0%) and PPV (28.1% vs. 19.1%). Genotype-specific PPVs were highest for HPV16 mRNA (47.7%), followed by HPV33 (39.2%) and HPV31 (32.2%), all exceeding corresponding DNA-based estimates. Conclusion: Genotype-specific HPV mRNA triage offers superior risk discrimination compared to cytology, supporting more targeted, efficient, and accessible cervical cancer screening. 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

Human papillomavirus (HPV) is a recognized oncogenic agent in several epithelial malignancies, though its role in esophageal squamous lesions remains unclear. Esophageal squamous papilloma and papillomatosis are rare, often benign lesions, but increasing evidence suggests possible associations with high-risk HPV genotypes and a non-negligible risk of dysplasia and malignant transformation. This narrative review summarizes current evidence on epidemiology, clinical features, histopathology, and diagnostic approaches, emphasizing advanced endoscopic imaging techniques that improve lesion detection and characterization. Management relies primarily on complete endoscopic resection with histological and virological evaluation. While small, non-dysplastic solitary lesions may not require routine surveillance, multifocal or high-risk HPV-positive cases warrant closer follow-up. Standardized HPV testing and long-term prospective studies are needed to better define the oncogenic potential and inform surveillance and treatment strategies. Full article

Background/Objectives: Cervical cancer remains a significant global health issue, with high incidence and mortality rates, particularly in Eastern Europe. Despite the availability of vaccines against human papillomavirus (HPV), regular screening remains crucial for prevention. Testing for HPV, alone or combined with cytology, has become an alternative to traditional methods. However, since many HPV infections are transient, additional tests are needed to identify high-risk cases. Methods: This study aims to generate detailed statistical data specific to the Bulgarian population, reinforcing the necessity of incorporating updated European methodologies and algorithms for the prophylaxis and prevention of cervical carcinoma. Results: By evaluating epidemiological trends, risk factors, and the effectiveness of current preventive measures, this research seeks to provide a strong foundation for enhancing cervical cancer screening and early detection programs. This method improves triage by identifying women who require further evaluation, ensuring timely referrals for colposcopy or biopsy. Conclusions: While liquid-based cytology (LBC) and HPV genotyping improve detection, the introduction of p16/Ki-67 dual staining has enhanced risk stratification, offering higher sensitivity and specificity for detecting high-grade lesions. These advancements are improving cervical cancer screening and patient outcomes. Full article

Background: Texture analysis (TA) has shown promise in characterizing intratumoral heterogeneity from imaging data. We add to the literature that shows its capability to differentiate oropharyngeal cancers based on HPV status. Methods: Multislice CT analysis was done in 120 patients with confirmed OP SCC: a single 5 mm region of interest was placed on three consecutive homogeneous CT slices per patient. Texture features were extracted by using gray-level co-occurrence matrices averaged per patient. HPV status (via p16 IHC and molecular confirmation) and differentiation grade (i.e., good, moderate, and poor) were recorded. Non-parametric statistical tests assessed differences between subgroups. Results: Seven texture parameters (i.e., angular second moment, contrast, sum of squares, sum entropy, entropy, inverse difference moment, and difference variance) differed significantly between HPV+ and HPV− tumors (all p < 0.05). HPV+ tumors exhibited increased heterogeneity and complexity on CT imaging. No texture feature correlated with histological grade. Conclusions: This study adds to the growing evidence that CT-based TA can assess HPV status in OP SCC. TA may be promising, though it requires further validation as an adjunctive method integrating into radiomics workflows to develop predictive models for diagnosis, prognosis, and treatment planning. Full article

Cervical cancer (CC) is the gynecological cancer with the highest incidence and mortality worldwide. High-risk oncogenic human papillomaviruses (HPV) genotypes 16 and 18 are the primary risk factors for developing this female neoplasm, with them being the etiological agents of 70% of cervical cancers. Despite the availability of various prevention strategies, laboratory tests capable of detecting the disease in its previous and early stages, and multiple treatment schemes, CC incidence and mortality rates remain high, due in part to the population’s rejection or disinterest in the current type of sampling. An alternative that could encourage women to take better care of their gynecological health is the availability of tests that detect biomarkers in non-cervical samples with high sensitivity and specificity. The detection of biomarkers in non-cervical samples (blood, serum, plasma, urine, and vaginal fluids) may help reduce the discomfort associated with cervical sampling in patients, therefore promoting gynecological healthcare. This review discusses current diagnostic methods and recent advances in CC biomarkers detected in non-cervical samples, emphasizing their potential for diagnosis, prognosis, and patient monitoring. We further discuss the challenges and future perspectives of applying these biomarkers in clinical practice. The results of this review show that there is a considerable range of biomarkers proposed as alternative tools with high efficacy. Their identification in previous stages of the disease and routinely in non-cervical samples could help reduce the incidence and mortality rates of CC. Full article

Background/Objectives: Head and neck squamous cell carcinoma (HNSCC) ranks sixth in the world in terms of incidence. Small proline-rich proteins (SPRRs) are precursors of the keratinocyte envelope and act as substrates of transglutaminase. A change in SPRR expression is characteristic in a few types of cancer. Our aim was to determine the concentration of SPRR1A and SPRR2A in tumours samples obtained from 61 patients with HNSCC (OSCC, OPSCC, LSCC, HPSCC, NCSCC, and SSCC). Also, we aimed to determine the relationship between protein concentration and other clinical and/or demographic variables. Methods: An ELISA test was used to determine the concentrations of SPRR in the tumour tissue homogenates. Results: In margin samples, we found a statistically significant association between SPRR1A levels and nodal status (N) and between SPRR1A levels in tumours and margins with G2 histological grade. When we analysed the effect of tobacco and alcohol habits, we found a statistically significant difference between the SPRR1A and SPRR2A amount in smokers and non-smokers in margin samples. Also, we found a statistically significant difference between the SPRR1A and SPRR2A levels in tumour and margin samples obtained from patients that either abstain and occasionally or regularly consume alcohol. Furthermore, we found in tumour and margin samples from patients with concomitant diseases an association between SPRR1A and SPRR2A levels. Our results showed altered concentrations of SPRR1A at margins, depending on HPV status. Conclusions: These results suggest that differences in SPRR proteins are determined by disease status and unhealthy behaviours, which, in a wider perspective, can influence carcinogenesis. Full article

Background/Objectives: The HPV vaccine is highly effective and safe in preventing HPV infection. This study explored the relationship between HPV vaccination, HPV knowledge and awareness, and oral HPV infection prevalence among Indigenous Australian adults. Methods: Data were collected from a large convenience sample in South Australia in 2018–19, with annual follow-ups through 2022–23. The primary outcome was oral infection with HPV types 6, 11, 16, 18, 31, 33, 45, 52, or 58. The main exposure was HPV vaccination uptake status, which was categorised as unvaccinated, partially vaccinated (1–2 doses), or fully vaccinated (3 doses). Covariates included sociodemographic factors, general and sexual health behaviours, and HPV knowledge scores (HPV-KT). Risk ratios (RRs) for oral HPV infection were estimated using Poisson regression models. Results: Among the 1006 participants who completed at least one questionnaire and oral HPV test by 24 months, 81% were unvaccinated, 13% partially vaccinated, and 7% fully vaccinated. Fully vaccinated individuals had the highest HPV-KT scores (mean: 3.4) and the lowest oral HPV prevalence (5%). After adjusting for covariates, unvaccinated participants had a 1.08 times higher risk of oral HPV infection (95% CI: 1.00–3.11) compared to those fully vaccinated. Conclusions: Full HPV vaccination (three doses) is associated with lower oral HPV infection and greater HPV knowledge. The protective effect appears stronger than for partial vaccination or no vaccination, underscoring the importance of completing the full vaccine series to reduce oral HPV burden. Full article

Background/Objectives: Human papillomavirus (HPV) is a prevalent sexually transmitted infection globally and is linked to the development of various cancers. While several international studies have investigated the incidence of high-risk HPV (HR-HPV) in bladder cancers, no such research has been conducted within the UK. Conflicting results in previous studies leave uncertainty regarding the role of HR-HPV in bladder cancer. This study aimed to assess the presence of HR-HPV DNA in bladder cancer specimens from the UK. Methods: A total of 55 fresh bladder specimens, including 4 benign and 51 malignant samples, were analysed using polymerase chain reaction (PCR) and Sanger sequencing to detect 12 HR-HPV types. Immunohistochemistry (IHC) was used to confirm the expression of the HPV E7 protein in HR-HPV-positive samples. Results: HR-HPV DNA was detected in 33% of bladder cancer specimens, with HPV16, HPV35, and HPV52 being the most prevalent types. None of the benign samples tested positive for HR-HPV. IHC confirmed HPV E7 protein expression in 81% of HR-HPV DNA-positive cancer samples. Conclusions: The findings suggest that HR-HPV may play a role in a subset of bladder cancers in the UK. The absence of HR-HPV in benign bladder specimens supports its potential involvement in cancer progression. Further research is needed to clarify the mechanistic role of HR-HPV in bladder cancer development. 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

Background/Objectives: Cervical Intraepithelial Neoplasia (CIN) is a significant risk factor for the development of invasive cancer, and the histological detection of High-Grade CIN (CIN2+) during screening generally indicates the need for surgical removal of the lesion; cervical conization is the current gold standard of treatment. The recurrence risk for disease is reported to be up to 30%, based on data in the literature. Follow-up protocols mainly rely on High-Risk Human Papillomavirus (hrHPV) detection at six months post-treatment; if negative, this is considered the test of cure. This approach assumes that all patients have an equal risk of disease recurrence, regardless of individual characteristics. The objective of this study was to evaluate the individual recurrence risk using a mathematical model, analyzing the weight of various parameters and their associations in terms of recurrence development. Methods: We retrospectively examined 428 patients treated for CIN2+ at San Raffaele Hospital in Milan between January 2010 and April 2019. Clinical and pathological data were recorded and correlated with disease recurrence; three different variables, known to behave as significant prognostic factors, were analyzed: hrHPV persistence, the surgical margin status, Neutrophil–Lymphocyte Ratio (NLR), along with their relative associations. Data were used to engineer a mathematical model for the identification of different risk classes, allowing for the risk stratification of cases. Results: Surgical margins status, hrHPV persistence, and a high NLR index were demonstrated to act as independent and significant risk factors for disease recurrence, and their different associations significantly correlated with different recurrence rates. The mathematical model identified eight classes of recurrence probability, with Odds Ratios (ORs) ranging from 7.48% to 69.4%. Conclusions: The developed mathematical model may allow risk stratification for recurrence in a hierarchical fashion, potentially supporting the tailored management of follow-up, and improving the current protocols. This study represents the first attempt to integrate these factors into a mathematical model for post-treatment risk stratification. 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