Search Results (694)

Background/Objectives: This study evaluated the diagnostic accuracy of cervical cytology, CINtec^® (p16/Ki-67 dual staining), and PD-L1 immunohistochemistry, individually and in combination with high-risk HPV (HR-HPV) testing, for identifying histologically confirmed cervical lesions ranging from CIN1 to invasive carcinoma. Methods: We conducted a prospective cross-sectional study including 114 patients who underwent cervical cytology, CINtec^®, PD-L1 staining, HPV genotyping, and histopathologic confirmation at a tertiary clinical center between September 2024 and September 2025. Sensitivity, specificity, PPV, NPV, and ROC performance were calculated for each test across lesion categories. Multivariable logistic regression models incorporating HR-HPV status were used to assess added predictive value. Results: All tests showed poor performance for CIN1 (cytology AUC 0.488; CINtec^® 0.374; PD-L1 0.366). Diagnostic accuracy improved markedly with lesion severity. For CIN3, CINtec^® demonstrated the highest discriminative ability (AUC 0.826), with cytology and PD-L1 also performing well (AUC 0.820 and 0.753). Cytology achieved the strongest ROC performance for CIN2+ (AUC 0.937), CIN3+ (0.913), and invasive carcinoma (0.887). PD-L1 consistently showed lower accuracy across categories. Cytology + HR-HPV demonstrated the highest AUC across all lesion categories. Conclusions: Cytology and CINtec^® exhibited strong diagnostic accuracy for high-grade lesions, while PD-L1 showed limited utility as an independent screening marker. Combining cytology with HR-HPV testing enhanced predictive performance across all lesion categories. These findings support the continued use of cytology-based triage and highlight CINtec^® as a valuable adjunct for high-grade disease detection. Because this study used a high-prevalence referral cohort, specificity may be overestimated and not representative of population-based screening. Full article

Objectives: The main objective of the present study was to evaluate the outcomes of patients referred for colposcopy due to human papillomavirus (HPV) positivity and/or abnormal cytology. Methods: A retrospective analysis was conducted on women who underwent colposcopy between January 2015 and December 2023. Demographic data and results of the colposcopy result were obtained from the patient files and the electronic gynecologic oncology clinic database. Results: A total of 2682 patients were included in the analysis. A cervical biopsy identified a cervical intraepithelial neoplasia (CIN)2+ (CIN2, CIN3, and invasive cancer) lesions in 361 patients (13.5%), while endocervical curettage (ECC) identified a CIN2+ lesions in 148 patients (5.6%). A total of 74 patients exhibited CIN2+ lesions in both cervical biopsy and ECC samples, while 74 patients displayed CIN2+ lesions exclusively in ECC samples. The distribution of high-risk HPV positivity in 435 patients with CIN2+ lesions revealed that 47.5% of patients were positive for HPV type 16, while 8.9% were positive for HPV type 18. A total of 50% of all patients diagnosed with CIN2+ lesions by ECC alone were found to be positive for HPV type 16 (37/74). Of the 116 patients with high-risk HPV positivity and normal cytology, 34 (29.3%) were high-risk HPV other-positive. Conclusion: HPV type 16 and 18 positivity represents the highest-risk groups in terms of CIN2+ lesion development. ECC should be considered, in particular, in women with HPV 16 positivity. Colposcopy should be performed immediately, rather than after one year, in women with high-risk HPV other-positivity and normal cervical cytology, in order to increase the detection rate of CIN2+ lesions. Full article

Background/Objectives: Persistent human papillomavirus (HPV) infection can lead to malignancies of the cervix, vulva, vagina, penis, anus, and oropharynx. The increasing incidence of HPV-related head and neck cancers has raised concerns regarding potential occupational exposure and transmission risks among healthcare workers. This study aimed to systematically evaluate the evidence on occupational HPV transmission in healthcare settings. Methods: A systematic review of the literature was conducted using three electronic databases (PubMed, Scopus, and Web of Science) from inception to August 2025, following PRISMA 2020 guidelines. A total of 34 studies met the inclusion criteria and were included in the review. Expert opinions and practical recommendations from members of the European Society of Gynaecological Oncology (ESGO) Prevention Committee were included to support interpretation of the results. Results: The available literature on occupational HPV transmission was limited, with a paucity of high-quality studies. Nevertheless, existing data suggest a potential occupational risk, particularly during aerosol or smoke-generating procedures performed for cervical intraepithelial neoplasia or cervical cancer. Several studies reported the detection of HPV DNA in surgical smoke or on instruments used during such procedures, indicating possible exposure among healthcare workers. Conclusions: Although current evidence is insufficient to definitively classify HPV infection as an occupational disease, available data indicate a potential exposure risk for healthcare workers involved in HPV-related procedures. Preventive measures, like personal protective equipment, should be emphasized. HPV vaccination has been recommended by some professional societies for healthcare workers performing gynecological procedures, though further research is needed to evaluate vaccine efficacy beyond the standard age range and its cost-effectiveness in this context. Full article

Many countries have introduced HPV screening and vaccination programs to reduce the burden of cervical cancer. In Poland, before 2023, HPV vaccination was available only on an individual, non-universal basis, using all types of vaccines, while in 2023, a nationwide vaccination program for boys and girls aged 12–13 years was introduced alongside updated screening guidelines. This retrospective study analyzed 2296 HPV-positive test results obtained from adult patients in Poland, including demographic data, HPV genotypes distribution, infection intensity, and cytological findings. HPV genotyping was performed using the Anyplex™ II HPV28 assay. HR-HPV genotypes accounted for 64.53% of all detected infections, with the highest prevalence observed in individuals aged 26–35 years of both sexes. HPV-18 was significantly more frequently in women (p = 0.0430), whereas HPV-53 predominated in men (p = 0.0030). Men more often presented low-intensity infections, while women showed higher viral load. Multigenotypic infections occurred in 46.5% of cases, particularly among younger patients (p < 0.001), and were significantly associated with LSIL changes in cytology. The HSIL type correlated most strongly with HPV-16 (p < 0.001). These findings confirm the high burden of HR-HPV infections in the Polish adult population and provide an essential epidemiological baseline for evaluating the impact of universal HPV vaccination and updated screening strategies. Full article

Background: Vulvar cancer mainly affects postmenopausal women, but its incidence is rising among younger individuals due to persistent HPV infection. Validated diagnostic biomarkers remain lacking, though circulating exosomal microRNAs (exomiRs) have recently emerged as promising liquid biopsy tools across various cancers. Objective: The purpose of this study was to identify a panel of dysregulated plasma-derived extracellular vesicle (EV)-associated miRNAs, hereafter referred to as exosomal micro-RNAs, as liquid biopsy markers for the detection of vulvar cancer and for assessment of HPV-positivity. Methods: Five healthy donor (HD) and 10 vulvar cancer samples underwent Next-Generation Sequencing to screen for differentially expressed exomiRs. The seven most dysregulated and four stably expressed exomiRs were subsequently analyzed in 81 cancer and 60 HD samples by qRT-PCR. Differential expression was determined by the 2^−ΔΔCT method. Binary regression was used to construct an exomiR panel. HPV status was assessed using mass spectrometry. Results: Five single exomiRs showed a statistically significant dysregulation in cancer patients compared to healthy controls: miR-143-3p, miR-223-3p, miR-451a, miR-4516 and miR-151a-5p. The combination of six exomiRs resulted in a panel with superior diagnostic ability (p < 0.001; ROC-AUC = 0.805; 95% CI: 0.726–0.884) in distinguishing cancer patients from HDs. A model consisting of miR-223-3p, miR-143-3p and miR-451a could discriminate HPV-positive from -negative (p = 0.003; ROC-AUC = 0.939), and a model of miR-4516, miR-143-3p, miR-16-5p and miR-451a was predictive of lymph node positivity (p < 0.001, ROC-AUC = 0.786). Multivariate Cox regression showed that a model of downregulated miR-16-5p and upregulated miR-451a was significantly associated with poorer survival (p = 0.023). Conclusions: This study indicates the future potential of exomiRs as diagnostic and prognostic liquid biopsy markers for vulvar cancer. Full article

(1) Background/Objectives: Human papillomavirus (HPV) testing is hypothesised to detect cervical intraepithelial neoplasia grade 3 (CIN3) earlier than cervical cytology, which could translate into several clinical benefits. This study aimed to confirm that HPV testing detects CIN3 lesions of smaller size (or linear extension) and to assess whether this is associated with a decreased risk of stromal microinvasion (≤3 mm) (microinvasive or stage IA1 cervical carcinoma). (2) Methods: The study was conducted in a referral centre for cervical pathology in Italy. Eligible were 3744 patients aged 30–64 years who underwent local excision of the cervix between 1992 and 2021 and were diagnosed with CIN3, with or without microinvasion. Data were analysed using logistic and multinomial regression models. (3) Results: Overall, 1156 (30.9%) CIN3 cases were detected by the HPV test, and 2588 (69.1%) by cervical cytology. The lesion size was smaller in HPV test-detected CIN3 (median, 6 mm; interquartile range (IQR), 4–8 mm) than in cytology-detected CIN3 (median, 7 mm; IQR, 5–9 mm; p < 0.001). HPV test-detected CIN3 was over 50% less likely to have a size >6 mm combined with massive glandular crypt involvement. Stromal microinvasion occurred in 20/1156 (1.7%) HPV test-detected lesions versus 87/2588 (3.4%) cytology-detected lesions (p = 0.006), corresponding to an approximately 50% lower age-adjusted risk. The smaller size of HPV test-detected CIN3 and its lower degree of glandular crypt involvement interacted additively, rather than multiplicatively, in reducing the risk of stromal microinvasion. Over 46% of the association between detection mode and stromal microinvasion was explained by the size/involvement composite variable. (4) Conclusions: HPV testing detects CIN3 lesions of smaller size than cervical cytology. HPV test-detected CIN3 has a lower risk of stromal microinvasion. This association is mediated to a substantial extent by the smaller lesion size and the less extensive glandular crypt involvement, which interact in an additive manner. These findings may have other important clinical implications. First, the prevalence of disease persistence after treatment may decrease. Second, smaller lesions are likely to be treated with more limited excisions. Third, this may contribute to a lower rate of preterm birth in subsequent pregnancies. Full article

In this work, we evaluate the efficiency of a DNA purification protocol from gynecological samples using locally synthesized Fe₃O₄@SiO₂ magnetic microparticles and a low-cost, guanidinium thiocyanate (GITC)-free lysis buffer. The microparticles were characterized by SEM, EDS, FTIR, and magnetic measurements, confirming the formation of compact silica-coated aggregates with suitable magnetic responsiveness for rapid and complete capture. Using this material in combination with a simple, GITC-free lysis buffer, we achieved DNA extraction yields comparable to those obtained with standard methods based on chaotropic salts. The purified DNA showed high compatibility with molecular assays for the detection of Chlamydia trachomatis, Ureaplasma urealyticum, Mycoplasma hominis, and human papilloma virus. Clinical validation demonstrated excellent diagnostic performance, with only a few discrepancies observed in samples near the detection threshold of qPCR, a limitation shared with commercial kits. Overall, the method represents a low-cost, safe, and sustainable alternative for routine clinical and epidemiological applications, compared to methods based on chaotropic salt buffers. Furthermore, it reduces reliance on imported commercial consumables and minimizes the handling of hazardous reagents. Full article

Background/Objectives: HPV vaccination is safe, effective, and recommended at ages 11–12, yet uptake remains suboptimal. Serious video games may offer an innovative strategy to deliver brief, engaging education during clinic visits. This qualitative paper, embedded within a mixed-methods study, examined adolescents’, parents’, and healthcare providers’ (HCPs’) perceptions of the acceptability, usability, and perceived clinical applicability of HPV Detective, a tablet-based digital game designed to provide HPV-related education to parent–child dyads during pediatric clinic wait times. Methods: Eight adolescent–parent dyads (N = 16) and three HCPs from university-affiliated pediatric clinics participated in 30–60-min semi-structured Zoom interviews. Interviews were audio-recorded, transcribed, and thematically analyzed by two coders, with discrepancies resolved by consensus and reviewed by a third researcher. Results: Participants identified five key dyadic themes and four HCP themes. Adolescents described the gameplay as intuitive and enjoyable, highlighting interactive challenges and realistic avatars. Parents valued the clarity of HPV information and noted that the game helped initiate health-related conversations. Both adolescents and parents suggested enhancements including voice narration and greater customization and agreed that the game was well suited for 10–15-min clinic wait times, with text messaging preferred for follow-up. HCPs emphasized challenges such as parental hesitancy and competing clinical demands and viewed the game as a feasible adjunct to support vaccine-related discussions. Conclusions: Findings suggest the acceptability, usability, and perceived clinical applicability of a brief, clinic-based digital game for HPV-related education and engagement among adolescents and their parents. Full article

Background/Objectives: Self-collection devices are more widely used than ever for detecting sexually transmitted infections and cervical cancer. Despite this, we still lack a clear understanding of how well these tools actually collect and release the necessary molecular samples. This study compared the in vitro uptake and release performance of commonly used self-sampling devices for total proteins, nucleic acids, and episomal human papillomavirus type 16 (HPV-16) DNA. Methods: An artificial cervicovaginal fluid composed of phosphate-buffered saline supplemented with serum and nucleic acid extracts was serially diluted 2-fold. Each dilution was applied for 5 min to the external surfaces of a vaginal veil (Vaginal Veil Collector V-Veil UP2^TM device), a flocked swab (FLOQSwabs^®), and a commercial vaginal tampon. Non-woven surgical tissue and plastic film served as controls. Total proteins and nucleic acids were quantified by spectrophotometry, and HPV-16 DNA by real-time quantitative PCR. Results: Recovery rates for proteins and nucleic acids were highest for the vaginal veil (81% and 91%), followed by the swab (66% and 70%) and non-woven tissue (44% and 47%). In contrast, the tampon and plastic film performed poorly, releasing less than 30% of proteins and negligible amounts of nucleic acids. Episomal HPV-16 DNA release was highest for the veil (89%), compared with the swab (57%), non-woven tissue (37%), tampon (4%), and plastic film (2%). Conclusions: The vaginal veil demonstrated superior uptake and release of proteins, nucleic acids, and HPV-16 DNA at physiological concentrations. Its non-absorbent structure allows high saturation with efficient release of genital components, including microbial genomes, whereas vaginal tampons retained these components, limiting analytical recovery. Full article

Cervical cancer is a largely preventable disease, with over 90% of cases caused by persistent infection with human papillomavirus (HPV). Despite the availability of HPV vaccination and cervical screening, incidence rates in Canada have been rising since 2015, particularly among underserved populations. This study investigates contributing factors behind cervical cancer diagnoses in Eastern Ontario over a two-year period to identify gaps leading to failures in prevention and screening. A retrospective chart review was conducted for cervical cancer cases diagnosed between January 2022 and December 2023 at two regional cancer centres in Eastern Ontario. Cases were categorized as screen-detected, inadequately screened, or system failure, based on prior screening history and care processes. Data was collected on patient, screening, and cancer characteristics. Of 132 cases, 22 (16.7%) were screen-detected, 73 (55.3%) were inadequately screened, and 37 (28.0%) were attributed to healthcare system failure. Later-stage disease was significantly more common in the latter two groups. Thirty-one (23.5%) cases presented with palliative diagnoses, and 18 (13.6%) individuals died within 2.5 years. Inadequate screening was associated with rurality, deprivation, and lack of a primary care provider. System failures included false-negative Pap tests, loss to follow-up, and misapplication of screening guidelines. This study evaluated failures in cervical cancer prevention, which led to cervical cancer diagnoses in Eastern Ontario. Gaps included suboptimal screening participation, lack of access to care, health care system breakdowns, and limitations of the Pap test. Findings provide concrete suggestions for eliminating cervical cancer in Canada. Full article

Background/Objectives: Diffuse sinonasal exophytic papillomas (DSNEPs) are rare entities, with similarities to recurrent respiratory papillomatosis (RRPs). DSNEP treatment is usually based on surgical excision, but the recurrence rate is high. Bevacizumab injections have been increasingly used as an adjuvant option for RRP, but their role in DSNEP treatment remains unknown. The current study describes the preliminary experience, safety profile, and exploratory outcomes of sublesional bevacizumab injections following surgical excision. Methods: We undertook a retrospective, single-centre study of a cohort of patients diagnosed with DSNEP between 2011 and 2018. All patients were treated with surgical excision and sublesional bevacizumab injections. The effect of bevacizumab was evaluated using a severity score developed to quantify lesion size and the extent of affected areas in each patient. Results: Seven patients diagnosed with DSNEP were treated. All patients were male, with a median age at diagnosis of 42 years [38–44.5]. Human papillomavirus (HPV) DNA was detected in all patients: HPV-11 in six cases (85.7%) and HPV-6 in one case (14.3%). Bevacizumab was injected into the submucosa of their surgical sites. The median follow-up was 55.5 months [40.85–82.73]. Most patients (85.72%) presented recurrence, with a median of 3 years [1.5–4]. A statistically significant reduction in the severity score was observed (p = 0.017), although this finding cannot be attributed solely to bevacizumab due to study design limitations. No relevant complications were reported. Conclusions: Nasal sublesional bevacizumab injections were well tolerated and feasible as an adjuvant approach to DSNEP. Larger prospective studies are needed to confirm its safety and assess its potential benefit. Full article

Evidence on the contribution of human papillomaviruses (HPVs) to the development of esophageal papillomas is still controversial. Esophageal papillomatosis (EP) is considered an exceedingly rare, but distinct entity within esophageal proliferations, with about 57 cases published so far. Tissues derived from an EP case and from non-EP esophageal papillomas were investigated for the presence of HPVs and virus-positive specimens were subsequently analyzed for transcriptional activity and surrogate markers of infection. Low-risk type HPV6 DNA was detected in a subset of the esophageal papillomatous tissues, including EP, and a variant isolate belonging to lineage A. In the EP tissue, the abundant expression of the viral E6/E7 mRNA and the presence of HPV6-specific E1^E4 transcripts, the latter indicative of productive viral infection, were detected. An analysis of HPV-specific neutralizing antibodies in sera obtained from the EP case during natural infection as well as after HPV vaccination revealed that, despite extensive manifestation, HPV6-specific antibodies were absent during natural infection and only elicited after repeated HPV immunizations. Although limited by a small sample size, this exploratory study suggests a possible involvement of HPV6 in the development of EP. Furthermore, this study may contribute to the evidence distinguishing EP from less extensive forms of non-EP esophageal squamous papillomas. Full article

Cervical cancer remains a major global public health concern, with persistent infection by high-risk human papillomavirus (hrHPV) types recognized as the primary etiological factor. This review explores the multifactorial nature of the disease, focusing on the complex interplay between host genetic susceptibility and epigenetic alterations that drive cervical carcinogenesis. Evidence from genome-wide association studies (GWAS) is discussed, highlighting the contribution of specific genetic loci, predominantly within the HLA region, to susceptibility to HPV infection and disease progression. In parallel, the review examines the molecular mechanisms by which the viral oncoproteins E6 and E7 promote genetic instability and epigenetic reprogramming, including histone modifications and dysregulation of non-coding RNAs. Particular emphasis is placed on DNA methylation, affecting both the viral genome and host genes such as FAM19A4, CADM1, PAX1, and MAL, as a promising biomarker for triage and detection of high-grade intraepithelial lesions (CIN2+). Finally, the review evaluates currently available methylation-based assays and self-sampling devices, highlighting their potential to enhance diagnostic accuracy and increase participation in cervical cancer screening programs. Full article

Background and Objectives: Kidney transplant recipients (KTRs) face increased susceptibility to persistent viral infections due to prolonged immunosuppression. While high-risk human papillomavirus (HR-HPV) infection is known to be more prevalent in this population, little is known about the co-occurrence of HPV with human herpesviruses (HHVs) infection in the female genital tract. This study aimed to investigate the presence, dynamics, and potential interactions between HR-HPV and HHVs infections—including HSV-1, HSV-2, EBV, CMV, HHV-6, and HHV-7—in female KTRs during the first year after transplantation. Materials and Methods: A total of 39 female KTRs and 79 age-matched healthy controls were enrolled in the study. Cervicovaginal swabs from recipients were obtained at three time points: two weeks, six months, and one year post-transplantation. HPV DNA was screened using PCR, followed by high-risk HPV genotyping and quantitative viral load assessment using two commercial PCR kits. HHVs were detected using a multiplex PCR assay. Results: HPV DNA was detected in 98% of the KTRs at least once during follow-up, which was significantly greater than in the controls (38%). HR-HPV was identified in 46% of the recipients over the study period, with the highest viral load at one year post-transplantation. HHVs were detected in 72% of the KTRs but not in 43% of the controls (p < 0.01), with EBV and CMV being the most common. Coinfection with HR-HPV and HHVs occurred in 46% of the recipients but not in the controls. Samples containing both EBV and CMV had significantly higher HR-HPV viral loads than samples with no HHVs or with single/other HHV combinations (p < 0.01). All cervical intraepithelial neoplasia patients were found to have combined HPV and HHV infection. Conclusions: Female KTRs present a high burden of both HR-HPV and herpesviruses infections, with increased HPV viral loads. These findings suggest a potential synergistic interaction between HR-HPV and herpesviruses in the immunosuppressed setting. Full article

Human papillomavirus (HPV) vaccination may eventually eradicate oncogenic vaccine-targeted HPVs but only with a strategy that also protects unvaccinated individuals. We compared the impact of gender-neutral and girls-only vaccination strategies on the indirect and direct protection of unvaccinated and vaccinated young women against HPV16/18 infection using HPV16/18 seropositivity and PCR positivity 3–7 years post vaccination as the outcome measure. A total of 33 Finnish communities were randomized to one of three vaccination strategies: bivalent gender-neutral HPV vaccination (Arm A), girls-only HPV vaccination (Arm B), or control hepatitis B vaccination (Arm C). All individuals born between 1992 and 1995 and residing in these communities (n = 80,272) were invited to participate. Overall, 11,662 males and 20,513 females consented, corresponding to vaccination coverages of 25% and 45%, respectively, in 2007–2009. Between 2010 and 2014, 11,396 cervical samples were collected from 18-year-old participants and subjected to high-throughput PCR-based HPV genotyping. In addition, serum samples were obtained from 8022 unvaccinated women under 23 years of age residing in Arm A (n = 2657), Arm B (n = 2691), or Arm C (n = 2674) communities during the pre-vaccination (2005–2010) and post-vaccination (2011–2016) periods. To assess indirect vaccine effects using PCR and serological outcomes in unvaccinated women, we compared reductions in HPV16/18 prevalence from baseline within the gender-neutral and girls-only vaccination arms, using the control arm as a reference. A significant decrease in seroprevalence between the pre- and post-vaccination periods was detected in the gender-neutral communities for both HPV16 (seroprevalence ratio = 0.64) and HPV18 (0.72), whereas no comparable reductions were observed in the girls-only or control communities. In contrast, a significant reduction in HPV18 PCR-based prevalence from baseline to the post-vaccination period was observed in both the gender-neutral (0.32) and girls-only (0.61) communities. However, after accounting for ratios of seroprevalence rations for secular trends, the corresponding decrease in HPV18 seroprevalence was no longer statistically significant. Vaccine efficacy (VE) in Arm A or Arm B versus Arm C of vaccinated women measured the direct protection of vaccinated women by vaccination strategy. HPV16/18 VEs varied between 89% and 96% with some indication of herd effect against HPV18. Robust effectiveness of vaccination against PCR-confirmed cervical HPV16/18 infections, along with rapid indirect protection against HPV16/18 and HPV18 infections, was evident even with vaccination reaching only 25% and 45% coverage. Our results suggest that vaccine efficacy and herd effect induced by gender-neutral 2vHPV vaccination sets the stage for comprehensive HPV eradication, including the unvaccinated in the vaccinated communities. Full article