Search Results (153)

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

Persistent high-risk human papillomavirus (HR-HPV) infection is closely associated with the development of cervical intraepithelial neoplasia (CIN) and cervical cancer. In recent years, the potential impact of viral co-infections on this process has also been investigated. This study investigated the presence of HR-HPV, HSV-1/2, and HHV-8 DNA in formalin-fixed paraffin-embedded (FFPE) cervical biopsy samples, as well as their association with lesion severity. A total of 276 FFPE cervical tissue samples were evaluated. Viral DNA was detected by real-time PCR. The samples were histopathologically classified as normal/non-dysplastic, low-grade (LSIL), and high-grade (HSIL) lesions. HR-HPV DNA was detected in 112 samples (40.6%), with the highest prevalence observed in the 30–39 age group (51.2%). Among the HPV-positive cases, 46.5% (52/112) had single-type infections, 32.1% (36/112) had multiple-type infections, and 21.4% (24/112) were untypable. Together, these categories accounted for all HPV-positive samples. The most common genotype was HPV-16 (16.7%). HHV-8 and HSV-2 DNA were not detected. HSV-1 DNA was detected in only three non-dysplastic, HPV-negative cervical samples. In conclusion, HR-HPV DNA was detected in 40.6% of cervical biopsy samples and showed a significant association with increasing histological severity, highlighting its critical role in the progression of cervical lesions. Although the absence of HHV-8 and HSV-2 suggests a limited contribution of these viruses to cervical disease, the use of a single real-time PCR assay limits the ability to draw generalized conclusions regarding their clinical relevance. Further large-scale, multicenter studies employing both tissue-based and serological approaches are needed to validate these findings and to better understand the dynamics of viral co-infections in cervical disease. 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

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 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

Cervical cancer screening is crucial for early detection and prevention. In Japan, women with negative intraepithelial lesion or malignancy (NILM) and high-risk human papillomavirus (HR-HPV) positivity are recommended retest for 12 months, rather than immediate colposcopy. International guidelines differ, and often prioritize early colposcopy for persistent HPV16/18 infections. This study evaluates Japan’s current screening approach, and identifies areas for improvement. A retrospective cohort study analyzed cervical cancer screening data from Saga Prefecture (2019–2021), assessing follow-up adherence, colposcopy referral rates, and CIN2+ and CIN3+ detection among NILM/HR-HPV+ cases. Among 27,789 individuals screened, 2248 (8.1%) were NILM/HR-HPV+. Follow-up adherence after 12 months was 54.4%. Of these, 132 with cytological abnormalities underwent colposcopy, revealing CIN2+ in 27.3% of cases. Additionally, 561 women with persistent NILM/HR-HPV+ underwent colposcopy, with CIN2+ in 7.6% and CIN3+ in 3.9% of cases. Japan’s current NILM/HR-HPV+ management strategy could delay the detection of high-grade cervical lesions. International guidelines favor earlier colposcopy referrals, particularly for HPV16/18+ cases. To improve cervical cancer prevention, Japan should consider a risk-based stratification model, enhance follow-up adherence, expand colposcopy access, and develop a national patient tracking system. Adopting primary HPV-based screening could attain the best global practices, facilitating earlier detection and reducing cervical cancer. 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

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

Background/Objectives: Squamous cell carcinoma of the anus (SCCA) remains a relatively rare form of cancer linked to high-risk human papillomavirus (HR-HPV) infection; however, its incidence has been increasing globally. Anal cytology and HR-HPV testing can identify precursors, though standardized screening guidelines are still lacking. This study aimed to assess the correlation between high-resolution anoscopy (HRA) findings and primary screening results through PAP-HPV co-testing in high-risk patients. Methods: A retrospective, single-center study was conducted collecting data from the joint multidisciplinary anal cancer clinic of Piero Palagi Hospital in Florence (Italy), between August 2019 and September 2022. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy of anal cytology, HR-HPV testing, and PAP-HPV co-testing were assessed. Results: In 577 HRAs, histology revealed 31 AIN2+ lesions (5.4%) and 220 AIN1 lesions (38.1%), while 326 (56.5%) were negative. Cytology alone showed a sensitivity of 74.2% and specificity of 63.3% for AIN2+ lesions, while HR-HPV testing alone had a sensitivity of 96.8% and specificity of 38.1%. Co-testing demonstrated 100% sensitivity and a 100% NPV for AIN2+ lesions. Among men who have sex with men (MSM), no significant differences in outcomes were observed between HIV-positive and HIV-negative patients, likely reflecting similar high-risk behaviors and effective HIV treatments. Conclusions: Co-testing with anal cytology and HR-HPV testing provides the most reliable screening for high-grade lesions (AIN2+), surpassing the reliability of individual methods. Tailored co-testing strategies are crucial for early detection and effective prevention in high-risk groups. Full article

The aim of this study was to investigate the distribution of human papillomavirus (HPV) genotypes among cervical cancer cases in Moroccan women living in the Souss-Massa region. A total of 155 formalin-fixed, paraffin-embedded cervical tissue samples were tested for the presence of HPV DNA using a semi-nested PCR assay. HPV genotypes were identified using a direct Sanger sequencing assay. The prevalence of HPV was 85.8%. HPV DNA was found in 87.5% of high squamous intraepithelial lesions (HSIL) cases and 85.7% of invasive cervical cancer (ICC) cases. Ten distinct HPV genotypes were identified, including seven high-risk HPV (HR-HPV) genotypes and three low-risk HPV (LR-HPV) genotypes. Among HR-HPV genotypes, HPV16 was the most prevalent in both HSIL and ICC, detected, respectively, in 42.9% and 55.6% of cases. In ICC cases, HPV18 was the second most common genotype detected, in 10.3% of cases. In addition, HPV31, 33, 35, 45 and 58 were detected in 10.4% of ICC cases. LR-HPV genotypes, namely HPV62, 70 and 87, were detected in 2.4% of ICC cases. Adenocarcinoma (ADC) accounted for 4.1% of ICC cases, with HPV 16 and HPV 18 identified in 60% and 40% of these cases, respectively. Overall, our findings show that the genotypes covered by the bivalent and nonavalent HPV vaccines account, respectively, for 65.4% and 74.6%. These results highlight the importance of introducing HPV vaccination and primary HPV testing for mass screening in Morocco in order to effectively prevent and manage cervical cancer and ultimately save women’s lives. Full article

Background: Human papillomavirus (HPV) infections in men remain under-researched despite their critical role in disease transmission and the increasing incidence of HPV-related cancers. This study investigates the clinical and molecular characteristics of anogenital HPV infections in men, emphasizing genotype prevalence, diagnostic methods, and lesion variability. Methods: A cross-sectional study was conducted on 70 men aged 18–65 years with clinically diagnosed anogenital HPV infection. Lesions were characterized by morphology and location. HPV DNA was analyzed using INNO-LiPA (INNOvative Line Probe Assay), Hybrid Capture II (HC II), and polymerase chain reaction (PCR) assays to determine genotype distribution. Associations between clinical features and HPV genotypes were assessed using multivariate statistical analyses. Results: Lesions varied in morphology, with verrucous (52.86%) and papular (30%) types being the most common. Localization patterns showed predominance on the penis radix (34.29%) and shaft (27.14%). Molecular testing revealed HPV DNA in 88.57% of the cases using INNO-LiPA, compared to 45% and 40% with HC II and PCR, respectively. Low-risk (LR) genotypes, particularly HPV6, dominated single infections, comprising 68.57% of the cases, while high-risk (HR) genotypes accounted for 20%. Mixed LR and HR infections were observed in 14.29% of the lesions, with greater diversity noted in distal genital regions. Notably, condyloma plana and lesions on the inner prepuce exhibited a higher prevalence of HR and mixed infections. Age and lesion duration showed trends toward older patients and longer disease duration in cases involving perianal and extragenital condylomas, though these findings were not statistically significant. No direct correlation between lesion type or localization and specific genotypes was identified, underscoring the heterogeneity of HPV clinical manifestations in men. Conclusions: Anogenital HPV infections in men exhibit significant heterogeneity in lesion morphology, localization, and genotype distribution. HR HPV genotypes were detected in a notable proportion of benign lesions, underscoring their potential role in disease progression. INNO-LiPA proved superior in diagnostic accuracy, highlighting the need for standardized and cost-effective diagnostic approaches for men. Further research is crucial to elucidate HPV’s clinical impact in men and inform prevention and treatment strategies. Full article

High-risk human papillomavirus (HR-HPV) and other sexually transmitted infections (STIs-O) are promoters to the development of cervical cancer (CC), especially when they co-exist. This study aims to determine the prevalence of the major STIs-O and the rate of co-infection in women previously diagnosed with HR-HPV infection. For this observational study, 254 women aged 25–65 years who were being followed up for HR-HPV infection (without a CC history) were recruited at a hospital’s Gynaecology Department from February 2024 to November 2024. Their endocervical specimens were collected and processed for HR-HPV, Chlamydia trachomatis, Neisseria gonorrhoeae, Mycoplasma genitalium, and Trichomonas vaginalis detection by RT-PCR using commercially available reagents and equipment. The overall rate of infection was 38.6% for HPV and 4.3% for ITSs-O (3.8% in HPV-negative women and 5.1% in HPV-positive women). The presence of ITSs-O in women aged 25–34 was higher in those with a persistent positive result for HR-HPV (20.0% vs. 4.2%). Diverse multiple co-infections were found in HPV-positive women, whilst some single STIs-O were found in HPV-negative women. These results support the benefits of STI-O screening beyond an HR-HPV positive result, especially in those women under 35 years old. Full article

Background: Molecular triage testing for high-risk human papillomavirus (hrHPV)-based cervical cancer screening can be used in self-sampling, potentially reducing unnecessary colposcopies and increasing attendance. However, its commercial value remains underexplored. This study used headroom analysis to estimate the maximum reimbursable price (MRP) at which molecular testing would be cost-effective for the triage of hrHPV-positive women, compared with cytology. Methods: A validated microsimulation Markov model for the Dutch cervical cancer screening program evaluated three triage scenarios: (1) cytology (base scenario), (2) molecular testing in self-samples only (scenario I), and (3) molecular testing on self- and GP-collected samples (scenario II). Test sensitivity and specificity ranged from 65% to 95%, with a threshold of EUR 20,000 per life-year gained. Results: In scenario I, MRPs ranged from EUR 244 (85% sensitivity, 75% specificity) to EUR 435 (95% sensitivity, 95% specificity). In scenario II, molecular testing was cost-effective across all parameters, with MRPs from EUR 162 (65% sensitivity, 65% specificity) to EUR 624 (95% sensitivity, 95% specificity). Increasing the sensitivity did not significantly affect life-years gained (due to the low mortality of cervical cancer in the Netherlands), but increased specificity did reduce the number of unnecessary colposcopies. Conclusions: Enhancing the specificity of molecular triage testing will improve its commercial value by reducing colposcopy referrals without affecting the number of life-years gained. Full article

Background/Objectives: Human Papillomavirus (HPV) cross-infection among couple’s partners is a widespread event and could lead to persistent infections. Unfortunately, the influence of male sexual partners of HPV-positive women on their cervical lesions and the potential role of HPV vaccines have been under-investigated. We evaluated the HPV prevalence in male partners of HPV-infected women, focusing on the possible correlation between partners’ cervical lesions and the role of HPV vaccination. Methods: Two samples, genital and urethral swabs, were collected for each of the 90 patients recruited. HPV-DNA detection was carried out by the Allplex HPV28 detection assay. Results: HPV prevalence was 66.7% (60/90); high-risk HPV (hrHPV) genotypes were detected in 90% (54/60) cases and multiple infections in 55% (33/60). The most frequent hrHPVs were HPV31 (p = 0.0265) and HPV52 (p = 0.002), found in 18.3% (11/60) of cases, and HPV53 (p = 0.0116) in 16.7% (10/60). Statistical analysis showed a higher probability of a less severe cytological diagnosis with the increase in the number of genotypes detected (p = 0.0146). Among the HPV-positive partners of females with cervical lesions, 18.7% (6/32) and 62.5% (20/32) had vaccine genotypes of the quadrivalent and nonavalent vaccines, respectively. The nonavalent vaccine showed a significantly higher potential to prevent lesions (62.5% vs. 18.7%, p = 0.0001), with an absolute additional potential impact (AAI) of 31.1% in histological and 32.4% in cytological diagnoses. Conclusions: These preliminary results provide new insight into the correlation between the number of partner genotypes and the severity of cervical lesions and show promising results for the preventive potential of vaccinating male partners. Full article