Search Results (39)

Human papillomavirus (HPV) is a leading cause of several cancers, most notably cervical cancer, but also anal, penile, vulvar, vaginal, and oropharyngeal malignancies. While vaccines and screening technologies offer highly effective prevention, the global burden of HPV-induced cancers remains disproportionately high in low- and middle-income countries (LMICs). This literature review provides a comprehensive synthesis of the types, mechanisms, treatments, and prevention strategies associated with HPV-related cancers, while also highlighting regional disparities in healthcare access and infrastructure. It critically examines the barriers LMICs face in adopting life-saving interventions, such as limited healthcare infrastructure, vaccine hesitancy, funding gaps, and cultural stigma. The review further explores recent scientific and policy advances—including single-dose vaccination, self-sampling HPV tests, and senolytic therapies—that have the potential to reduce global health inequities. By connecting molecular biology with public health systems, this paper underscores the need for interdisciplinary solutions and equity-centered approaches to combat HPV-induced cancers worldwide. The findings emphasize that eliminating cervical cancer and other HPV-related diseases is not only a scientific goal but also a moral imperative requiring global collaboration and local action. Full article

Background: Anal cancer screening has allowed for the diagnosis of early-stage anal cancers; however, guidelines for the treatment of early anal cancers remain mixed given the scarcity of clinical trials and data. Management ranges from chemoradiation therapy to local surgical excision. Methods: This paper’s objective is to clarify the definition of early anal cancer and its management. Approval for this systematic review was obtained through PROSPERO [CRD42022304327]. Three independent reviewers screened the studies and performed data analysis, with conflicts resolved by a fourth reviewer. All information is presented according to the Preferred Reporting Item for Systematic Reviews and Meta-Analysis (PRISMA). The Grades of Recommendation, Assessment, Development, and Evaluation (GRADE) criteria were used to assess the certainty of the evidence. Results: The MEDLINE, EMBASE and Cochrane databases were queried with 628 articles screened. A total of 15 articles were selected for inclusion. Early anal cancer was most often defined as T1-2N0M0 anal cancer but also included Superficially Invasive Squamous Cell Carcinoma (SISCCA). There were various treatments assessed for outcomes including local excision, chemoradiation, and radiation. The studies reported overall survival, cancer-specific survival, recurrence-free survival, and/or colostomy-free survival, leading to significant heterogeneity amongst the studies. No meta-analysis was possible. Conclusions: Poor-quality studies exist for the evaluation of the most effective treatment modality for early anal cancer. Surgical excision alone with adequate margins has equivocal results, but data is poor. Chemoradiation is successful but may be overtreatment. Randomized controlled studies are needed, as screening will result in earlier anal cancer diagnoses. Full article

Inflammatory bowel disease (IBD), comprising ulcerative colitis (UC) and Crohn’s disease (CD), is a chronic condition marked by persistent intestinal inflammation of unknown etiology. Disease onset involves genetic predisposition and environmental factors that disrupt the intestinal immune homeostasis. The intestinal microbiome and immune response play pivotal roles in disease progression. Advances in molecular therapies and early interventions have reduced surgery rates; however, colorectal cancer (CRC) remains a significant concern, driven by chronic inflammation. In UC, the risk of UC-associated neoplasia (UCAN) increases with disease duration, while CD patients face elevated risks of small intestine, anal fistula, and anal canal cancers. Endoscopic surveillance is advised for UCAN, but optimal screening intervals remain undefined, and no established guidelines exist for CD-associated cancers. UCAN morphology often complicates detection due to its flat, inflammation-blended appearance, which differs pathologically from sporadic CRC (sCRC). UCAN is frequently surrounded by dysplasia, with p53 mutations evident at the dysplasia stage. IBD-associated gastrointestinal cancers exemplify inflammation-driven carcinogenesis with distinct molecular mechanisms from the adenoma-carcinoma sequence. This review explores the epidemiology, risk factors, clinical and pathological features, current surveillance practices, and molecular pathways underlying inflammation-associated cancers in IBD. 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

This study aimed to evaluate the burden of HPV-related hospitalization and mortality in Greece, with a focus on invasive cervical cancer and lip, oral cavity, and pharyngeal (LOCP) cancers. A retrospective query using data from the Greek Statistical Office and Eurostat was executed. The query included hospital admission and standardized mortality rates (SDRs) on cervical dysplasia and cervical, vulvar, and vaginal; anal; penile; and LOCP cancers. The hospitalization rate for invasive cervical cancer decreased over time, exhibiting a sharp decrease after 2010, while the hospitalization rate for LOCP cancer decreased after 2011, preceded by a sustained increase from 1996. The hospitalization rate of HPV-attributable diseases in total showed a declining tendency between 2013 and 2017. SDR due to cervical cancer showed a slightly decreasing trend in Greece and the European Union, while SDR due to LOCP cancer showed a slightly increasing trend in Greece, but a decrease in the European Union. The decline in hospitalization rates for HPV-related disease in Greece, especially for cervical cancer and dysplasia, and also the declining SDR for invasive cervical cancer in Greece and the EU, are indications of the positive public health impact of screening programs and the implementation of HPV vaccination. Full article

Rectal cancer is a significant global health concern, particularly amongst the elderly population, with rectal cancer accounting for approximately one-third of cancer cases in this population. Older adults often present with advanced disease stages and unique clinical manifestations, such as tumors closer to the anal verge and with greater size. Diagnosis typically involves a series of screening and imaging strategies, culminating in accurate staging through pelvic MRI, endoscopic ultrasound, and CT scan. Management of rectal cancer in older adults emphasizes individualized treatment plans that consider both the cancer stage and the patient’s overall health status, including frailty and comorbidities. A multidisciplinary approach, including a mandatory geriatric assessment, is essential for optimizing outcomes, in order to improve survival and quality of life for elderly patients with rectal cancer. Full article

Background: Anal HPV infection can cause squamous intraepithelial lesions (SILs), which are precursors of anal squamous cell carcinoma (SCC). The early detection of HPV infections and improvement of effective screening programmes are, therefore, essential to prevent progression from pre-cancerous lesions to SCC, especially in people living with HIV (PLWH), who represent a population at higher risk of HPV infection and associated lesions. Among prevention strategies, HPV vaccination is relevant too, but its efficacy in persons already infected by HPV is still debated. Methods: This is a retrospective single-center study on a cohort of PLWH who performed longitudinal screening for anal dysplasia and HPV infection. The screening included cytological and molecular analyses. Results: A total of 110 PLWH performed at least one anal HPV screening, with an overall prevalence of HPV infection of 86.4% [23.6% low risk (LR)-HPV and 62.7% high risk (HR)-HPV genotypes]. Abnormal cytology was demonstrated in 39.1% of subjects, of whom ASCUS 6.4%, LSIL 30.9% and HSIL 1.8%. In total, 80 patients (72.7%) had an available longitudinal screening. No patient developed SCC during follow-up. However, a high incidence of new cytological abnormalities and new HPV infections was observed. On the other side, clearance of some HPV genotypes was also frequent, confirming that HPV infection is a dynamic process. A CD4 cell count > 500/mmc was an independent predictor of HPV clearance. HPV vaccination was performed on 30.9% of patients. A trend toward an increased clearance of HPV genotypes included in 9-valent vaccine was observed in vaccinated patients (40.6% versus 30.8% in unvaccinated, p = 0.079). Conclusions: A high prevalence of HPV infection and SILs was observed in our cohort of PLWH. A high incidence of new HPV infections and HPV-associated lesions was also observed in the longitudinal cohort, highlighting the need of strengthening immunization programs and continuous screening for anal HPV infection. Whether HPV vaccination may be efficacious in patients already infected by HPV remains to be determined. Full article

In 2012, the Department of Visceral Surgery of the Lausanne University Hospital CHUV implemented a dedicated high-resolution anoscopy (HRA) outpatient clinic for surveillance and follow-up purposes. This 10-year longitudinal study analyzed 537 patients (2214 visits) using a structured screening protocol. Dysplastic lesions were detected in 49% of patients, predominantly low-grade squamous intraepithelial lesions (LSILs, 74%). Among LSIL cases, 6% progressed to high-grade squamous intraepithelial lesions (HSILs) within 24 months, reaching 25% cumulative progression at 36 months. Of HSIL patients, 3% developed carcinoma in situ after 48 months. Notably, no invasive carcinoma was observed during the follow-up. Four patients diagnosed with squamous cell carcinoma at initial screening were treated with chemoradiotherapy, and one required salvage surgery. Independent risk factors for the presence of higher-stage precancerous lesions (≥HSILs) were the presence of high-risk HPV genotypes (OR 14.5, 95% CI 5–42.2, p < 0.001), detectable HIV viral load (OR 5.4, 95% CI 1.8–16.7, p = 0.003), and symptoms at the first screening visit (OR 3.2, 95% CI 1.1–9.9, p = 0.04). HIV-positive status was associated with a trend towards an increased risk of progression (OR 2.79, p = 0.073). These findings highlight the importance of systematic follow-up and early intervention in high-risk populations to prevent anal cancer progression. Full article

Men who have sex with men (MSM) and people with HIV are at increased risk of anal HPV infection and cancer. This study aimed to assess the prevalence of anal HPV among MSM with HIV (MWH) and without HIV (MWoH), as well as among MSM under and over 35 years. Factors associated with infection from high-risk (HR) HPV were investigated. This retrospective cohort analysis included MSM receiving care at IRCCS San Raffaele, Milan, Italy, with at least one HPV test collected from 2014 to 2023. Among 1577 MSM, 1427 (90%) were MWH. At first screening, 87.6% were had HR-HPV and MWoH were significantly younger, as compared to MWH. Cytological abnormalities were more frequent among younger MSM, while high-grade lesions were more frequent among those over 35 years of age. In multivariate regressions, the risk of ≥1 HR-HPV genotype at first and last screening was associated with younger age (adjusted odds ratio, aOR (95% confidence interval): 0.33 (0.18, 0.59); 0.34 (0.18, 0.58), p < 0.001) and concomitant STI (aOR 2.74 (1.59, 5.08), p < 0.001; 1.68 (1.09, 2.67), p: 0.023). A discrepancy between the recommend and actual age for screening was found. As a younger age and concomitant STIs were associated with infection by ≥1 HR-HPV, we promote a more tailored screening approach for both MWH and MWoH. Full article

Antiretroviral therapy (ART) has significantly extended the lifespan of people living with Human Immunodeficiency Virus (HIV) or Acquired Immunodeficiency Syndrome (AIDS), thereby transforming the disease into a manageable chronic condition. However, this increased longevity has led to a higher incidence of non-AIDS-defining cancers (NADCs) among this population. In this holistic review, we explore the complex interactions between HIV, ART, and cancer development, focusing on how ART influences tumor initiation and progression in people living with HIV/AIDS (PLWHA). Our findings from this reveal several critical aspects of cancer risk in PLWHA. Firstly, while ART restores immune function, it does not fully normalize it. Chronic immune activation and persistent inflammation continue to be prevalent, creating a conducive environment for oncogenesis. Additionally, PLWHA are more susceptible to persistent infections with oncogenic viruses such as human papillomavirus (HPV) and Epstein–Barr virus (EBV), further increasing cancer risk. Some ART drugs have been implicated in genotoxicity and mitochondrial dysfunction, potentially promoting tumorigenesis. ART-induced metabolic changes, including insulin resistance and dyslipidemia, are also associated with heightened cancer risk. Common NADCs in PLWHA include lung cancer, liver cancer, anal cancer, and Hodgkin lymphoma, each with distinct etiologies linked to both HIV-related and ART-related factors. The interplay between HIV infection, chronic inflammation, immune restoration via ART, and the direct effects of ART drugs creates a unique cancer risk profile in PLWHA. Although ART reduces the incidence of AIDS-defining cancers, it does not confer the same protective effect against NADCs. Persistent HIV-related inflammation and immune activation, despite viral suppression, are key factors in cancer development. Additionally, long-term exposure to ART may introduce new oncogenic risks. These insights highlight the need for integrated cancer screening and prevention strategies tailored to PLWHA. Future research is needed to focus on identifying biomarkers for early cancer detection and developing ART regimens with lower oncogenic potential. Healthcare providers should be vigilant in monitoring PLWHA for cancer and adopt comprehensive screening protocols to mitigate the increased cancer risk associated with ART. Full article

Background: This study represents a follow-up analysis of the AnusGynecology (ANGY) study. Methods: This prospective, cross-sectional, single-center study recruited women for concomitant cervical and anal screening of HPV genotypes and cytology during a single appointment. All women with findings of either HPV or any type of dysplastic lesions on anal smears were offered follow-up in a specialized high-resolution anoscopy (HRA) outpatient clinic, representing the study cohort for this follow-up study. Results: Overall, 275 patients (mean age 42 ± 12) were included. Among them, 102 (37%) had cervical high-risk (HR) HPV. In total, HPV was (incidentally) revealed in 91 patients (33%) on anal smears, while any degree of anal squamous intraepithelial lesion (SIL) was found in 30 patients (11%), 6 if which were high-grade SIL (H-SIL). Furthermore, 10 out of 19 biopsies were positive (3 H-SIL lesions). Only half (48/91, 53%) of the women agreed to undergo the recommended specialized follow-up evaluation. Of them, 18 (38%) were diagnosed with dysplastic lesions (9 low grade (L-SIL) and 9 H-SIL, respectively) on biopsies, while the remaining visits revealed no abnormalities. Multivariable analysis revealed cervical HR-HPV infection (OR 4, 95% CI 2.2–7.5) and anal intercourse (OR 3.1, 95% CI 1.7–5.9) as independent risk factors for anal HR-HPV infection. Conclusions: Close follow-up of these women is hence strongly recommended. Full article

Over the last decades, the incidence of anal cancer has increased worldwide. The discovery of the HPV virus as its primary cause and the natural progression of the disease, involving precancerous lesions, have resulted in significant interest in screening for anal cancer. The use of cytology testing, high-risk HPV DNA research, high-resolution anoscopy, and their combination has been adopted with variable success in detecting anal HPV precancerous lesions. Various studies have been carried out to evaluate the sensitivity and specificity of these techniques in different populations. High-risk populations for developing anal cancer have been identified through study of incidence and prevalence. Therefore, different scientific societies and experts worldwide have provided different recommendations for screening, but a universal approach has not yet been established. The inhomogeneity of different risk groups, the variable accessibility to specifical techniques, and the lack of data regarding the cost–benefit ratio of screening are the main problems to address in order to define a consensus guideline acceptable worldwide. The purpose of this paper is to provide a comprehensive review of the literature on HPV precancerous lesions and its screening, particularly after the release of recent recommendations. Full article

The data from the literature show that women undergoing a LEEP due to CIN3 have a greater risk of having subsequent high-grade anogenital intraepithelial neoplasia or cancer, and the risk is greater for vaginal cancer than for anal and vulvar cancers. It is hypothesized that the laparoscopic hysterectomy procedure may cause a higher incidence of VaIN in hysterectomized women. There are few studies addressing this issue, and they show mixed results. This study aimed to investigate the incidence of high-grade or severe VaIN in the population of women undergoing hysterectomy for CIN3 or benign uterine disease and illustrate the treatment options and follow-up. Methods: This retrospective study was conducted on 170 women who underwent a laparoscopic hysterectomy due to high-grade cervical intraepithelial neoplasia (CIN3) or benign gynecological disease. The follow-up strategy included performing a cotest and colposcopy with biopsy if necessary. The median time between primary treatment and a diagnosis of high-grade VaIN was 18 months. Results: High-grade or severe VaIN was found in eight patients after hysterectomy (4.7%). All cases of high-grade VaIN occurred in women with persistent HPV infection. The most frequent genotype was 16. Women hysterectomized due to CIN3 showed an eight-fold greater risk than women hysterectomized due to benign disease of developing high-grade VaIN. The risk of VaIN is low in women hysterectomized due to benign disease. The risk of developing VaIN is greater in women with viral persistence. Conclusion: All these elements suggest that it is a history of HPV-related disease of the lower genital tract and viral persistence, rather than hysterectomy itself, that should be considered risk factors for the development of high-grade VaIN. After hysterectomy, patients with a history of CIN should undergo annual screening with vaginal dome cytology and HPV testing. Full article

The incidences of anogenital HPV-related cancers in women are on the rise; this is especially true for anal cancer. Medical societies are now beginning to recommend anal cancer screening in certain high-risk populations, including high-risk women with a history of genital dysplasia. The aim of this study is to investigate national anogenital HPV cancer trends as well as the role of demographics, deprivation, and ethnicity on anogenital cancer incidence in England, in an attempt to better understand this cohort of women which is increasingly affected by anogenital HPV-related disease. Demographic data from the Clinical Outcomes and Services Dataset (COSD) were extracted for all patients diagnosed with anal, cervical, vulval and vaginal cancer in England between 2014 and 2020. Outcomes included age, ethnicity, deprivation status and staging. An age over 55 years, non-white ethnicity and high deprivation are significant risk factors for late cancer staging, as per logistic regression. In 2019, the incidences of anal and vulval cancer in white women aged 55–74 years surpassed that of cervical cancer. More needs to be done to educate women on HPV-related disease and their lifetime risk of these conditions. Full article

The human papillomavirus is the most common sexually transmitted infection in the world. Most HPV infections clear spontaneously within 2 years of infection; however, persistent infection can result in a wide array of diseases, ranging from genital warts to cancer. Most cases of cervical, anal, and oropharyngeal cancers are due to HPV infection, with cervical cancer being one of the leading causes of cancer death in women worldwide. Screening is available for HPV and cervical cancer, but is not available everywhere, particularly in lower-resource settings. HPV infection disproportionally affects individuals living with HIV, resulting in decreased clearance, increased development of cancer, and increased mortality. The development of the HPV vaccine has shown a drastic decrease in HPV-related diseases. The vaccine prevents cervical cancer with near 100% efficacy, if given prior to first sexual activity. Vaccination uptake remains low worldwide due to a lack of access and limited knowledge of HPV. Increasing awareness of HPV and access to vaccination are necessary to decrease cancer and HPV-related morbidity and mortality worldwide. Full article