Search Results (59)

The most severe premalignant lesion of glandular epithelium of the cervix is adenocarcinoma in situ (AIS). In most cases it is associated with persistent human papillomavirus (HPV) infection and most often occurs in women in the fourth decade of life. In most high-income countries, primary screening has shifted to HPV testing, while cytology is used for patient triage. Even with current robust screening protocols, their sensitivity for glandular lesions remains limited. Diagnosis of AIS obtained by biopsy, brushing or curettage is confirmed by excisional methods and pathohistological verification. Therapy depends on the patient’s lifestyle and reproductive age. In our case, we present a nulliparous patient with persistent ASC-US, multiple-type HPV infection without HPV 16 and 18 types, and AIS which was diagnosed after conization, follow-up and two biopsies with curettage of cervical canal. Our case report highlights limitations in detection of glandular lesions and need for caution in patients with persistent and seemingly low-grade cytological abnormalities, notably in young patients with high-risk HPV types. Full article

Background/Objectives: Cervical cancer remains a major cause of morbidity and mortality among women worldwide, marked by stark geographic and socioeconomic disparities. Preventable via HPV vaccination and screening, progress toward elimination varies widely across and within countries. This narrative review synthesizes the epidemiology, including incidence, mortality, survival, and stage distribution, as well as risk factors and the coverage/equity of HPV screening and vaccination programs. Methods: Comprehensive searches were performed in PubMed, Web of Science, Scopus, and Google Scholar (no date restrictions; English only). Included were original epidemiological studies, systematic reviews, meta-analyses, and international reports on burden, risk factors, or prevention indicators. Data were qualitatively synthesized into three themes: epidemiological patterns, risk factors, and screening/prevention programs. Results: Persistent high-risk HPV infection causes nearly all cervical cancers, predominantly HPV16/18, with regional variation in other types. Strong co-factors include HIV immunosuppression, early sexual debut, multiple partners, high parity, long-term oral contraceptive use, and smoking. Inequalities in incidence, late diagnosis, and survival are driven by socioeconomic disadvantages, low education, rural residence, and poor health system access. Screening ranges from cytology/VIA to primary HPV testing, but coverage is low and inequitable in high-burden settings. HPV vaccination has expanded yet faces major gaps in low- and middle-income countries. Conclusions: Cervical cancer burden concentrates in low-resource and marginalized populations. Global elimination demands accelerated, equitable scale-up of HPV vaccination and screening, alongside health system strengthening and barrier reduction. Full article

Background: Cervical cancer is associated with Human Papillomavirus (HPV) infection. Besides cervical cancer, oro-pharyngo-laryngeal or uro-genital cancers are also reported. The HPV vaccine has been strongly recommended for school age children. However, the parents’ or guardians’ hesitancy remains. Methods: This is a mixed-method study in which the parents or guardians of school children, aged 10–18 years, were enrolled voluntarily. Their general demographic data, knowledge, attitudes, and awareness of vaccine accessibility, healthcare cost entitlement of the children, types of school affiliation, education administration areas where the schools were located, and the presence of a healthcare professional in family were analyzed by multiple logistic regression analysis adjusted with all studied variables to define the significant associated factors with the parents’ or guardians’ HPV vaccine acceptance (p < 0.05). In-depth interviews were subsequently performed with the selected participants until the qualitative data were saturated. Thematic analysis was applied, and the results of the two study methods were integrated to explore the reasons for vaccine acceptance or hesitancy. Results: A total of 943 questionnaire respondents were enrolled, among whom 75.8% were female and 86.4% were parents. A total of 663 (70.3%) participants accepted the HPV vaccine. Parents’ or guardians’ knowledge and attitudes, awareness of vaccine accessibility, type of school affiliation, the children’s healthcare cost entitlement, and the presence of a healthcare professional in the family were significantly associated with vaccine acceptance in the multivariate analysis (p < 0.05). The qualitative study revealed that misunderstanding of the vaccine’s safety and benefits combined with inadequate reliable information sources were associated factors with HPV vaccine hesitancy among the parents or guardians. Conclusions: Providing clear-cut knowledge about the HPV vaccine benefit vs. risk and clearing financial barriers for the parents or guardians of school children are advocated. Full article

Background: Persistent infection with high-risk human papillomavirus (HR-HPV) is the primary cause of cervical intraepithelial neoplasia (CIN) and cervical cancer. While HPV testing has become central to screening programs and the frequency of detecting multiple HPV genotypes has subsequently risen, the clinical relevance of multiple-type (MT) HPV infections remains uncertain. This study aimed to investigate the correlation between HPV infection type and the severity of cervical cytological and histological abnormalities. Methods: This retrospective study analyzed 340 women with dysplasia and 82 with histologically confirmed cervical cancer treated at the University Hospital Cologne between 2016 and 2019. HPV genotyping was performed using a DNA microarray detecting 41 HPV genotypes. Associations between infection patterns and cytological and histological findings were evaluated. Results: Multiple infections accounted for 42% of HPV-positive cases (119 among 284), showing a bimodal age distribution with peaks in patients ≤19 and ≥60 years. HPV16 and HPV18 were most frequently detected in worse than CIN3 lesions (CIN3+), mainly as single-type (ST) infections. Women with ST infections had a significantly higher risk of CIN3+ compared to those with MT infections (p = 0.004). HPV16 ST was significantly associated with CIN3+ compared to other HR-HPV ST (p = 0.046), whereas MT including HPV16 did not increase CIN3+ risk (p = 0.124). Co-infections involving alpha-9 clade types were associated with higher CIN3+ risk, while alpha-7 co-infections did not show an additive effect. Furthermore, coinfections involving two different alpha-9 or -7 were observed infrequently. Conclusions: Single HR-HPV infections are more strongly associated with high-grade cervical lesions than multiple infections, especially when HPV 16 is involved. These findings underscore the dominant oncogenic potential of HPV16 and suggest that intergenotypic interactions in MT infections may mitigate malignant progression. Full article

Cervical cancer remains a leading cause of mortality among women, particularly in regions with limited resources. Persistent high-risk human papillomavirus (HR-HPV) infection is the main etiological factor for CIN and cervical cancer. This study aimed to evaluate the association between HPV genotypes, age, and cytological findings and the presence of CIN2–3 in women presenting with abnormal cervical cytology. This cross-sectional study included 189 women with abnormal cytology who attended a tertiary center in Peru. All participants underwent partial HPV genotyping using the Cobas 4800 assay, colposcopic evaluation, and colposcopically directed biopsies, which served as the diagnostic reference. Sociodemographic characteristics and reproductive histories were also collected. Multiple logistic regression was performed to assess the associations among specific HPV genotypes, age, cytological results, and CIN2–3 outcomes. Most participants were between 30 and 59 years of age (76.7%), and multiparity was common (77.8%). The most frequent cytological abnormalities were ASC-US (36.0%) and LSIL (28.0%), followed by HSIL (20.1%). HPV16 was detected in 24.3% of cases, HPV18 in 2.1%, and other HR-HPV types in 73.6%. HSIL cytology showed high concordance with histological CIN2–3 (>95%). Logistic regression demonstrated that age ≥ 30 years (aOR 4.50, 95% CI 1.90–10.65) and HPV16 infection (aOR 4.19, 95% CI 1.95–9.00) were the strongest independent predictors of high-grade disease. HPV18 was rare and not significantly associated, whereas other HR-HPV types showed an inverse association with CIN2–3. HPV16 and age ≥ 30 years were the most significant predictors of CIN2–3 in women with abnormal cytology, underscoring the dominant oncogenic role of HPV16. Integrating HPV genotyping, cytological findings, and age into risk-stratified algorithms could optimize cervical cancer prevention, ensuring timely detection of high-grade lesions while minimizing overtreatment in low-risk populations. Full article

Background/Objectives: Colorectal cancer (CRC) is the third most common cancer and a leading cause of death worldwide. Identifying non-invasive, early indicators of CRC risk remains essential and could help reduce its health burden. Excess adiposity and chronic inflammation are major predisposing factors for precancerous adenomatous polyposis (AP) and CRC, while diet- or surgery-induced weight loss was associated with a reduced risk. Viral infections also represent cancer risk factors through direct or synergic mechanisms, though no definitive causal link has been established for CRC. Moreover, interest is growing on the role of oral viruses as predictors of disease. Methods: In this study, highly sensitive and specific Luminex-based screening assays were used to perform a comprehensive characterization of oral infections by Human Herpes (HHV), Polyoma (HPyV) and Papilloma (HPV) Viruses in CRC patients (N = 50), healthy controls (N = 46; normal weight, NW = 26; overweight, OW = 20), and high-risk individuals with obesity (N = 35) or adenomatous polyposis (AP, N = 22). Results: We observed increased HPyV prevalence in AP, and higher single and multiple β-HPV infection rates in AP and CRC compared to controls. A panel of β-HPV genotypes, including oncogenic HPV5, was overrepresented in CRC and high-risk groups, and some of them showed an association with the male sex. The prevalence of most infections decreased in the obese cohort following bariatric surgery, alongside weight loss and reduction of inflammatory markers. Furthermore, oral infections by viral types previously detected in CRC tissue and adjacent mucosa also declined after surgery. Conclusions: Altogether, these findings suggested a role for oral β-HPV types as potential sex- and lifestyle-related, modifiable indicators of cancer risk. Full article

Cervical cancer screening plays a crucial role in preventing invasive disease through early detection of high-grade lesions. However, traditional cytology and histology often fail to reliably differentiate between transient HPV infections and those likely to progress. This study investigates the feasibility of integrating molecular HPV testing into histopathological workflows using FFPE tissue samples to improve diagnostic precision. A retrospective analysis was conducted on 55 FFPE cervical specimens from patients undergoing colposcopy with biopsy or conization. The workflow included automated DNA extraction and real-time PCR-based HPV genotyping with the Seegene Anyplex II HPV28 assay. HPV DNA was detected in 56.4% of samples, with 21 genotypes, including multiple high-risk types. High viral loads correlated with high-grade lesions, supporting the clinical value of HPV quantification. Compared to histology, molecular analysis reduced potential overdiagnosis by confirming HPV absence in morphologically suspicious but HPV-negative lesions. Integrating viral load and genotyping improved risk stratification, optimizing colposcopy referrals and reducing unnecessary follow-ups. This study introduces a novel, fully automated molecular workflow applicable to FFPE samples, enhancing cervical cancer screening beyond traditional methods. Although based on a limited sample, the findings support the method’s potential for broader implementation and further validation in multicenter settings. 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: Understanding the regional distribution of human papillomavirus (HPV) genotypes is essential for guiding effective vaccination and screening strategies. This study aimed to assess the prevalence and distribution of HPV genotypes among unvaccinated women aged 30 years and older undergoing routine screening in Ankara. It also aimed to compare the frequencies of genotypes included and not included in current vaccines and to investigate their association with cervical smear cytology. Methods: This descriptive, cross-sectional, single-center study was conducted at Ankara Etlik City Hospital between 15 November 2024 and 15 February 2025. A total of 500 sexually active, unvaccinated women aged 30 years or older were enrolled. Cervical swab samples were analyzed for HPV DNA and genotypes using real-time PCR (28-type panel), and cytology results were retrospectively obtained from medical records. Results: HPV infection was detected in 18.2% of participants. Among HPV-positive women, 71.4% had single-type and 28.6% had multiple-type infections. The most common high-risk genotypes among HPV-positive individuals were HPV 16 (13.2%), HPV 18 (13.2%), and HPV 59 (13.2%). While 35.2% of HPV-positive cases included genotypes covered by the nonavalent vaccine, 64.8% involved at least one genotype not covered, mainly HPV 59, 44, and 51. HPV was detected in 17% of individuals with normal cytology, 19% of those with atypical squamous cells of undetermined significance (ASC-US), and 100% of cases with low-grade squamous intraepithelial lesion (LSIL) (p < 0.001). Conclusions: The findings emphasize the persistence of high-risk and non-vaccine-covered HPV types in the population, highlighting the need for updated vaccination policies and the development of broader-spectrum vaccines aligned with local genotype profiles. Full article

The skin is a complex organ, containing an intricate network of immune cells that are crucial for host barrier function and defence against pathogens. Human papillomavirus (HPV) exclusively infects the skin, and its lifecycle is intimately associated with epithelial cell division and differentiation. There are over 450 HPV types, 12 of which are classified as carcinogenic. The primary focus of this review is the epithelial immune response to HPV infection of the cervix during the initial stages of infection, productive infection, and disease progression. During the early stages of infection, cells are HPV-positive; however, there are no attributable histological changes to the epithelium. The HPV-infected cells have the capacity for innate sensing and signalling through toll-like receptors in response to viral nucleic acids. However, HPV has evolved multiple mechanisms to evade the innate response. During productive infection, all viral antigens are expressed and there are visible histological changes to the epithelium, including koilocytosis. Disease regression is associated with Tbet positive cells in the infected epithelium and the presence of CD4 and CD8 T cells in the lamina propria. Disease progression is associated with the overexpression of the E6 and E7 oncoproteins after integration of viral genomes into the host chromosomal DNA. Histologically, the epithelium is less differentiated, and changes to cells include a higher nuclear-to-cytoplasmic ratio and an increased mitotic index. Immune changes associated with disease progression include increased numbers of cells expressing suppressor molecules, such as FoxP3, Blimp-1, and HMGB1, and myeloid cell infiltrates with an M2-like phenotype. This review highlights the gaps in the understanding of the immune response in HPV-positive cervical neoplasia, and in regression and progression of disease. This knowledge is critical for the development of effective immunotherapies that reliably cause HPV-positive cervical neoplasia to regress. Full article

Background/Objectives: The 2020 American Cancer Society guidelines endorse human papillomavirus (HPV) testing as the preferred method for cervical cancer screening. This study aims to evaluate the concordance of HPV and cytology findings for cervical intraepithelial neoplasia (CIN) at a population level. Methods: A retrospective cohort review of cervical cytology, HPV testing, and biopsies for all patients at a single Oregon-based medical center was performed over 21 months. The performance of HPV and cytology in detecting high-grade CIN lesions was compared. Results: A total of 22,488 tests were evaluated, showing 7.5% abnormal cytology and 7.4% positive HPV. Among 574 patients who underwent co-testing and a subsequent biopsy, 345 had abnormal cytology, with 212 having abnormal biopsy results. HPV was positive in 455 cases, with 266 having abnormal biopsy results. Among 455 HPV-positive cases, there were 283, 104 and 33 cases of non-16/18, 16, and 18 types, respectively. Additionally, 35 cases had co-infection with multiple HPV types. Among the cases diagnosed as CIN3 on biopsy, 90.6% had positive HPV testing (N = 96), and 82.9% had abnormal cytology (N = 94). HPV testing demonstrated a slightly higher sensitivity (88.8% vs. 78.3%, p = 0.128) and lower specificity (27.1% vs. 48.9%, p < 0.01) compared to cytology for CIN2 and CIN3 diagnosis. Conclusions: HPV testing showed a similar sensitivity but lower specificity compared to cytology for detecting high-grade lesions. Full article

Cervical cancer is a largely preventable malignancy of the uterine cervix. The tendencies in cervical cancer morbidity and mortality have remained similar for the past decade, albeit with increasing frequency in low- and middle-income countries (LMICs). Moreover, in the majority of LMICs, cervical cancer is the second most prevalent cancer and the second most common cause of cancer-related death among reproductive-age women. High-risk human papillomavirus (HR-HPV) infections have been proven to be associated with up to 95% of cervical cancer cases, with HPV-16 and HPV-18 types being responsible for approximately 70% of all cervical cancers, with the other high-risk HPV types accounting for up to a further 25%. More recently, the latest data appear to confirm there is a change in the frequency of HR-HPV occurrence, especially HPV-16 and HPV-18, as a reflection of the implementation of preventive vaccination programs. Owing to the growing incidence of cervical cancer among reproductive-age women and with the development of cancer management approaches, fertility-sparing options have been proposed for early-stage cervical cancer management as an option for young women, especially those with unaccomplished reproductive desires. However, methods applied for this purpose (cold-knife conization, loop electrosurgical excision, trachelectomy) have variable outcomes and do not prevent risks of relapse. Multiple factors are involved in cervical cancer recurrence, even in cases treated at the early stage of the disease. In this review, the authors unveil whether HPV infection and virus type could be one of the key factors associated with cervical cancer recurrence after fertility-sparing surgery. Reviews of the literature reveal that recurrent and persistent HR-HPV infection is a strong predictor of cervical lesions’ relapse. In particular, HPV-16 and HPV-18 infections and their persistence have been reported to be associated with cervical cancer recurrence. HR-HPV genotyping before and after fertility-sparing surgery for cervical cancer could facilitate a personalized approach and improve the overall survival rate. Screening for HR-HPV is essential during the follow-up of cervical cancer-treated women and will help to predict possible cancer recurrence. Full article

Cervical cancer related to high-risk human papillomavirus (HR-HPV) is the second female cancer in Mauritania (Northwest Sahelian Africa). We assessed the distribution of HPV genotypes in Mauritanian women with high-grade cervical intraepithelial neoplasia (CIN2/3) or invasive cervical cancer (ICC). A prospective study was conducted in the Centre Hospitalier National, Nouakchott, Mauritania, to collect cervical biopsies among women suspected of CIN2/3 or cancer. HPV DNA detection and genotyping were carried out from formalin-fixed, paraffin-embedded biopsies using multiplex PCR (Human Papillomavirus Genotyping Real-Time PCR Kit, Bioperfectus Technologies Co., Taizhou, China). Fifty biopsies were included from women (mean age: 56.7 years) suffering from CIN2/3 (28.0%) and ICC (72.0%) which corresponded to 32 (64.0%) squamous cell carcinomas (SCC) and 4 (8.0%) adenocarcinomas (ADC). HPV DNA detection was successful in 47 (94.0%) samples. The most prevalent HR-HPV genotypes were HPV-45 (40.4%), HPV-16 (38.3%), HPV-39 and HPV-52 (23.4%), HPV-33 (17.0%), HPV-18 (14.9%), HPV-35 (4.2%), and HPV-56 (2.1%). The majority (93.6%) of HPV-positive biopsies contained at least one HPV type covered by the 9-valent Gardasil-9^® vaccine, and 40.9% were infected by multiple vaccine HPV genotypes. To eradicate cervical cancer in Mauritania, prophylactic HPV vaccination must be combined with primary molecular screening of cervical HR-HPV infection. Full article

Background: Human papillomavirus (HPV) infection is linked to several cancers, including anal and oral cancers. The incidence of anal cancer is particularly high among HIV-positive men who have sex with men (MSM). DNA methylation markers have shown promise as biomarkers for identifying precancerous lesions and cancer in HPV-infected individuals. The aim of this study was to investigate the correlation of DNA methylation with HPV infection in oral samples and the correlation of DNA methylation with lesion degree in the anal samples of HIV-positive MSM. Methods: This study investigated DNA methylation in oral and anal samples from HIV-positive MSM at the National Institute for Infectious Diseases (INMI) in Rome, Italy. Exfoliated oral epithelial cells and anal samples were collected and analyzed for 28 HPV genotypes using the Allplex 28 HPV assay. DNA methylation was assessed with the PrecursorM+ kit for oral samples and the AnoGyn kit for anal samples, focusing on the promoter regions of specific genes. Results: The study included 63 participants, with a median age of 49 and a median CD4+ count of 705 cells/µL. The oral samples showed HPV16 as the most common type, with 22% testing positive for DNA methylation. The anal samples exhibited HPV-related methylation changes linked to cytological lesions, with a 30% increase in the observed ddCt ratio. Significant differences were found in both ASCL1 and ZNF582 genes, particularly for HSILvsNILM and HSILvsLSIL lesions. Of the samples with an increased ddCt ratio, 80% were from patients over 35 years old, and multiple HPV infections were common. Conclusions: DNA methylation markers could be valuable in identifying high-risk HPV infections in oral samples and detecting potential precancerous lesions in anal samples. These markers may enhance the early detection and prevention strategies for HPV-related cancers in high-risk populations, with follow-up data indicating potential for monitoring lesion progression. Full article

The human papillomavirus (HPV) is a non-enveloped DNA virus transmitted through skin-to-skin contact that infects epithelial and mucosal tissue. It has over 200 known genotypes, classified by their pathogenicity as high-risk and low-risk categories. High-risk HPV genotypes are associated with the development of different types of cancers, including cervical cancer, which is a leading cause of mortality in women. In clinical practice and the market, the principal tests used to detect HPV are based on cytology, hybrid detection, and qPCR. However, these methodologies may not be ideal for the required timely diagnosis. Tests have been developed based on isothermal nucleic acid amplification tests (INAATs) as alternatives. These tests offer multiple advantages over the qPCR, such as not requiring specialized laboratories, highly trained personnel, or expensive equipment like thermocyclers. This review analyzes the different INAATs applied for the detection of HPV, considering the specific characteristics of each test, including the HPV genotypes, gene target, the limit of detection (LOD), detection methods, and detection time. Additionally, we discuss the tests available on the market that are approved by the Food and Drug Administration (FDA). Finally, we address the challenges and potential solutions for the large-scale implementation of INAATs, particularly in rural or underserved areas. Full article