Anal carcinoma - exploring the epidemiology, risk factors, pathophysiology, diagnosis, and treatment.

Anal carcinoma is a relatively rare tumor that accounts for approximately 2% of gastrointestinal malignancies and less than 7% of anorectal cancers. Most anal tumors originate between the anorectal junction and the anal verge. Risk factors for the disease include human papillomavirus infection, human immunodeficiency virus, tobacco use, immunosuppression, female sex, and older age. The pathogenesis of anal carcinoma is believed to be linked to human papillomavirus-related inflammation, leading to dysplasia and progression to cancer. Squamous cell carcinoma is the most common type of anal tumor, with an annual incidence of approximately 1 to 2 per 100000 persons. Treatment regarding anal cancer has emerged over time. However, chemoradiation therapy remains the mainstay approach for early localized disease. Patients with metastatic disease are treated with systemic therapy, and salvage surgery is reserved for disease recurrence following chemoradiation. This article aims to provide background information on the epidemiology, risk factors, pathology, diagnosis, and current trends in the management of anal cancer. Future directions are briefly discussed.

cIAP-2 protein is upregulated by human papillomavirus in oropharyngeal cancers: role in radioresistance in vitro.

BACKGROUND: High-risk human papillomaviruses are the causal agents of a subset of head and neck cancers. A previous transcriptomic analysis showed that cIAP2 protein, involved in cell survival and apoptosis, is upregulated in OKF6 oral cells that express HPV16 E6/E7. In addition, cIAP2 promotes radioresistance, a very important concern in HNC treatment. However, cIAP2 increase has not yet been evaluated in oropharyngeal carcinomas (OPCs), nor has been the role of cIAP2 in HNC radioresistance. METHODS: We carried out a descriptive-analytical retrospective study in 49 OPCs from Chilean patients. We determined the expression of cIAP2 at transcript and proteins levels using reverse-transcriptase -polymerase chain reaction and immunohistochemistry, respectively. HPV and p16 expression were previously analyzed in these specimens. In addition, SCC-143 HNC cells ectopically expressing HPV16 E6/E7 were analyzed for cIAP2 expression and after transfection with a siRNA for HPV16 E6/E7 knocking down. RESULTS: We found a statistically significant association between HPV presence and cIAP2 expression (p = 0.0032 and p = 0.0061, respectively). An association between p16 and cIAP2 levels was also found (p = 0.038). When SCC-143 cells were transfected with a construct expressing HPV16 E6/E7, the levels of cIAP2 were significantly increased (p = 0.0383 and p = 0.0115, respectively). Conversely, HPV16 E6 and E7 knocking down resulted in a decrease of cIAP2 levels (p = 0.0161 and p = 0.006, respectively). Finally, cIAP2 knocking down in HPV16 E6/E7 cells resulted in increased apoptosis after exposure to radiation at 4 and 8 Gy (p = 0.0187 and p = 0.0061, respectively). CONCLUSION: This study demonstrated for the first time a positive relationship between HPV presence and cIAP2 levels in OPCs. Additionally, cIAP2 knocking down sensitizes HNC cells to apoptosis promoted by radiation. Therefore, cIAP2 is a potential therapeutic target for radiation in HPV-driven HNC.

Lack of knowledge about the human papillomavirus vaccine among Brazilian adolescents: A cross-sectional study.

To analyze the distribution and factors associated with lack of knowledge about the human papillomavirus (HPV) vaccine among Brazilian adolescents.Cross-sectional study using the 2019 National School Health Survey among 17,805 Brazilian students of public and private schools, aged 13-17 years. The outcome variable was "lack of knowledge about the HPV vaccine" and the explanatory variables were sociodemographic, behaviors, knowledge, and health conditions. Logistic regression model was used to calculate Odds Ratio (OR) and 95% confidence intervals (95%CI). Spatial analysis techniques were used to determine the formation of clusters in the federated units with similar proportions of adolescents who were unaware of the vaccine. The lack of knowledge about the HPV vaccine was reported by 45.54% of Brazilian students. There was a higher chance of lack of knowledge having had sexual intercourse (OR 1.43; 95% CI 1.20-1.70); attending public school (OR 1.72; 95%CI 1.47-2.02) and located in the Northeast Region (OR 1.35; 95%CI 1.08-1.69). The lower chance of lack of knowledge were female gender (OR 0.41; 95% CI 0.35-0.48), higher maternal education (OR 0.62; 95% CI 0.50-0.77) self-rated health as Poor/very poor (OR 0.64; 95% CI 0.49-0.86) and receiving contraceptive counseling (OR 0.77; 95% CI 0.65-0.91). The proportion of lack of knowledge about the HPV vaccine was higher with the formation of High-High spatial clusters in the states of Maranhão, Piauí, and Pernambuco. Sociodemographic, health, and behavioral conditions and knowledge of students, as well as school characteristics, were associated with lack of knowledge about the HPV vaccine. A higher frequency of lack of knowledge about the HPV vaccine among adolescents was found in the states of the Northeastern Region.

Epidemiological characterization of oral focal epithelial hyperplasia in brown howler monkeys (Alouatta guariba clamitans).

BACKGROUND: Oral focal epithelial hyperplasia (FEH) is an uncommon infection affecting humans, chimpanzees, bonobos, and howler monkeys. This study describes 10 cases of free-ranging brown howler monkeys (Alouatta guariba clamitans) diagnosed with FEH and Alouatta guariba Papillomavirus 1 (AgPV 1). METHODS: We analyzed demographic characteristics, rescue conditions, clinical and pathological findings, and species-specific behavior factors in these cases. The study assessed the frequency of occurrence and potential contributing factors of FEH and AgPV 1 infection. RESULTS: The frequency of FEH was 8.13%. Most affected howlers were adult or geriatric males with comorbidities or stressful conditions. Clinical and pathological observations were consistent with AgPV 1 infection. Species-specific behaviors and environmental stressors were identified as contributing factors. CONCLUSIONS: FEH associated with AgPV 1 affected mainly adult or geriatric males with ongoing comorbidities or stressful conditions. Further research is needed to understand these factors for effective management.

Multifocal epithelial hyperplasia: an understudied infectious disease affecting ethnic groups. A mini review.

Focal Epithelial Hyperplasia or Multifocal Epithelial Hyperplasia (MEH), also known as Heck's disease, is considered a rare pathology of the oral mucosa associated with human papillomavirus types 13 and 32. For reasons not fully understood, MEH disproportionally affects specific populations of indigenous groups around the world. After the first reports in Native Americans, the epidemiology of the disease has been described in different geographical regions mainly related to particular indigenous populations, the majority of the studies are clinical case reports, but the biological determinants are still unknown. Some suggested risk factors include chronic irritation caused by smoking, a galvanic current, vitamin A deficiency, and/or a familial-genetic predisposition; however, the scientific evidence is not solid due the scarcity of case-control studies or longitudinal cohorts. In light of the evidence, further study of the pathology of MEH should be considered and proper clinical trials for effective treatments should be designed. The disease warrants further study as it is considered as neglected by research and it affects rural/remote population groups usually living in adverse socioeconomic conditions.

Prolonged detection of BPV2 in urine and blood of papillomatosis-affected cattle not grazing bracken fern.

BPV-2 infection can cause bladder infections in cattle that, when associated with bracken fern consumption, can progress to cancerous bladder tumors and also present as bovine enzootic hematuria (BEH). This study aimed to evaluate the prolonged natural BPV-2 infection in the blood and urine of cattle, excluding bracken fern consumption. Thirteen Girolando papillomatosis-affected cattle with no bracken fern contact history were monitored for 20 months. Blood, urine, and wart samples were collected for BPV-2 detection and clinical laboratory analyses. All animals showed the presence of BPV-2 in papillomas and blood, and 92.85% showed BPV-2 in urine, suggesting viral dissemination in the urinary tract. Despite all animals being infected with BPV-2, none showed BEH signs during the study. Thus, it was observed that BPV-2 infection alone didn't induce BEH over 20 months, implying a complex interaction with environmental factors or genetic predisposition. This underlines bracken fern consumption's critical role in urinary bladder carcinogenesis. The study underscores BEH's pathogenesis complexity, advocating longitudinal studies to comprehend BPV-2's role fully.

HPV and coronary diseases in menopausal women: an integrative review.

High-risk human papillomavirus (HPV) infection is associated with cervical cancer while low-risk HPV strains mostly cause benign lesions. Multiple studies have also associated HPV with coronary artery (CAD) disease in women. Furthermore, the climacteric period in women, triggers chronic inflammation and has major implications for CAD and associated lipid disorders. The association of HPV with coronary artery disease in climacteric women has few studies, and the objective of this review is to gather and analyse scientific data on the subject. This is an integrative review performed on PubMed and Google Scholar using the keywords "HPV", "coronary heart disease" and "climacteric", among these keywords the boolean operator AND and the publication date filter. (2018 onwards). Five articles were found, whose main results show presence of high-risk vaginal HPV in climacteric women. Climacterium and HPV were associated with a three-fold increased risk of CAD, as well as with factors related to menopause that promote atheroma formation, lipid disorders and chronic inflammation. Thus, these results support the association between HPV infection and CAD in climacteric women, possibly via chronic inflammation, hormonal factors related to menopause and dyslipidemia.

Translational control of papillomavirus mRNAs in the spotlight.

High-risk human papillomaviruses (HPVs) cause most cases of cervical cancer, a disease with an increasing impact worldwide. Recent studies have shown that the synthesis of viral oncoproteins is strongly subject to translational control. Thus, targeting the protein synthesis machinery might open novel avenues to develop innovative therapies aiming to improve patients' survival.

Detection of cytokines in cervicovaginal lavage in HIV-infected women and its association with high-risk human papillomavirus.

Background: Women living with HIV/AIDS (WLHA) have an increased prevalence of high-risk HPV infection (HR-HPV) and cervical intraepithelial neoplasia (CIN) and a greater risk of cervical cancer despite access to a new generation of antiretroviral therapy. The aim of this study is to evaluate the concentrations of different cytokines involved in the local immune response in WLHA, which is fundamental for understanding the pathogenesis of HPV-related cancer in this population. Methods: IL-1ß, IL-2, IL-4, IL-6, IL-10, IFN-γ, TNF-α, IP-10, GM-CSF, and MIP-1α were investigated in the cervicovaginal lavage (CVL) of 106 WLHA attending at Hospital Universitario Professor Edgard Santos in Salvador, Bahia, Brazil, during the period December 2019 to April 2023 by Luminex®. All participants were also tested for Chlamydia trachomatis and Neisseria gonorrhoeae and underwent colposcopy, Pap smear, and Nugent score. HIV plasma viral load (VL) and CD4 cell count were performed for all WLHA. Results: In this study, 22.6% (24/106) of WLHA were infected with HR-HPV. A higher proportion of patients with HR-HPV (66.7%) had detectable levels of IL-10 than those negative ones (40.2%, p = 0.02). More premenopausal women had either IL-6 (51.4%) or IP-10 (58.3%) than those in menopausal status (26.5% for IL-6 and 32.4% for IP-10, p = 0.013 and p = 0.011, respectively). Vaginosis was negatively associated with detection of IP-10 (24.2% vs. 61.4%, p < 0.001) and INF-γ (39.4% vs. 68.6%, p = 0.005). A positive association was detected for IL-1ß (66.7 vs. 37.1%, p = 0.005) and IL-10 (63.6% vs. 37.1%, p = 0.01). VL and CD4 were not associated with the studied cytokines. Conclusion: We demonstrated a positive association between IL-10 and HPV infection in CVL, suggesting the predominance of the Th2 response in HIV/HPV co-infected patients. However, further studies with longer follow-up will be needed to evaluate the association of IL-10 with HPV infection, CIN, and cervical cancer in WLHA.

Enhancing Cervical Cancer Screening with 7-Type HPV mRNA E6/E7 Testing on Self-Collected Samples: Multicentric Insights from Mexico.

Cervical cancer remains a significant public health issue, particularly in regions with low screening uptake. This study evaluates the effectiveness of self-sampling and the 7-type HPV mRNA E6/E7 test in improving cervical cancer screening outcomes among a referral population in Mexico. A cohort of 418 Mexican women aged 25 to 65, referred for colposcopy and biopsy due to abnormal cytology results (ASC-US+), participated in this study. Self-samples were analyzed using both the 14-type HPV DNA test and the 7-type HPV mRNA E6/E7 test. The study assessed the sensitivity, specificity, positive predictive value (PPV), and the necessity of colposcopies to detect CIN3+ lesions. Participant acceptability of self-sampling was also evaluated through a questionnaire. The 7-type HPV mRNA E6/E7 test demonstrated equivalent sensitivity but significantly higher specificity (77.0%) and PPV for CIN3+ detection compared to the 14-type HPV DNA test (specificity: 45.8%, p < 0.001). The use of the HPV mRNA test as a triage tool reduced the number of colposcopies needed per CIN3+ case detected from 16.6 to 7.6 (p < 0.001). Self-sampling was highly accepted among participants, with the majority reporting confidence in performing the procedure, minimal discomfort, and willingness to undertake self-sampling at home. Self-sampling combined with the 7-type HPV mRNA E6/E7 testing offers a promising strategy to enhance cervical cancer screening by improving accessibility and ensuring precise diagnostics. Implementing these app roaches could lead to a significant reduction in cervical cancer morbidity and mortality, especially in underserved populations. Future research should focus on the long-term impact of integrating these methods into national screening programs and explore the cost-effectiveness of widespread implementation.

Investigating under-reported human papillomavirus genotypes in Grenadian women through self-sampling for cervical cancer screening.

Objective: To compare the adequacy, agreement, and acceptability of Papanicolaou testing (cytology) for cervical cancer screening using self-collected samples compared to physician-collected samples in Grenada in the Caribbean. Furthermore, the study identifies the human papillomavirus (HPV) genotypes present among asymptomatic women testing positive for HPV, the etiologic cause of cervical cancer. Methods: Participants were divided into two groups and two cervical samples were collected from the women in each group: a self-collected sample and a physician-collected sample. Cervical specimens were tested for cytology and HPV. HPV genotyping was performed on positive specimens. Results: Self-collected samples were adequate and in agreement with physician-collected samples, showing no difference between the two sampling methods. Oncogenic high-risk HPV genotypes were identified in cervical samples which were positive for atypical squamous cells and low-grade squamous intraepithelial lesions. The high-risk HPV genotypes found, notably HPV 45 and 53, differed from those most commonly reported. Although the commonly reported high-risk genotypes HPV 16 and 18 were found, so were 31, 33, 35, 52, 66, 68, and 82. Conclusions: Using self-collection facilitated the discovery of unexpected HPV genotypes among asymptomatic women in Grenada. These findings add new information to the literature regarding cervical cancer and neoplasia screening and HPV genotypes in the Caribbean. This genotype information may impact surveillance of women with low-grade lesions, HPV vaccine selection, and possibly further vaccine research. Research regarding HPV in Caribbean pathology samples of cervical neoplasia and cancer is needed.

Interferon alpha-2b treatment for exophytic nasal papillomas and human papillomavirus infection.

OBJECTIVES: Exophytic Sinonasal Papilloma (ESP) is a benign tumor of the sinonasal tract. Complete surgical excision by endoscopic surgery is the treatment of choice. However, a high recurrence rate (36% at 5-year follow-up) is associated with this method, which may indicate the presence of microorganisms such as Human Papillomavirus (HPV). It is important to note that the standard treatment for ESP does not include antiviral drugs. In our study, we are testing the effectiveness of an interferon-containing drug in reducing recurrence and postoperative reactions in patients with ESP. METHODS: We included 78 patients aged 23-83 years with a confirmed diagnosis of ESP by rhinoscopy and nasal endoscopy and a positive PCR test for HPV in nasal scrapings. To compare the results, we divided the patients into main and control groups. The main group received recombinant human interferon after surgery, while the control group did not receive the drug. We performed a statistical analysis to compare the proportion of patients without reactive manifestations at different stages of the postoperative period, as well as to compare the proportion of patients with recurrent ESP at certain stages of observation. RESULTS: The introduction of recombinant human interferon accelerated the resolution of postoperative reactions and promoted the healing of the nasal mucosa after surgical removal of the ESP. We also found a statistically significant association between treatment with recombinant interferon and a reduction in the recurrence rate of ESP. CONCLUSION: According to the results of the study, it was found that in the main group of patients who received rhIFN-α2b (recombinant human Interferon alpha 2b) in the postoperative period, the frequency of relapses of ESP and the time of postoperative recovery were significantly lower than in patients in the control group who did not take the drug. LEVEL OF EVIDENCE: Cohort Study.

Potential Transcript-Based Biomarkers Predicting Clinical Outcomes of HPV-Positive Head and Neck Squamous Cell Carcinoma Patients.

Human papillomavirus (HPV)-positive Head and Neck Squamous Cell Carcinomas (HNSCC) comprise a particular cancer entity traditionally associated with better clinical outcomes. Around 25% of HNSCC are HPV positive, HPV16 being the most prevalent type. Nevertheless, close to 30% of the HPV-positive patients have an unfavorable prognosis, revealing that this type of tumor exhibits great heterogeneity leading to different clinical behaviors. Efforts have been made to identify RNA molecules with prognostic value associated with the clinical outcome of patients with HPV-positive HNSCC, with the aim of identifying patients at high risk of metastasis, disease recurrence, and poor survival, who would require closer clinical follow-up and timely intervention. Moreover, the molecular identification of those HPV-positive HNSCC patients with good prognosis will allow the implementation of de-escalating therapeutic strategies, aiming to reduce side effects, resulting in a better quality of life. This review compiles a series of recent studies addressing different methodological and conceptual approaches aimed at searching for potential gene expression-based biomarkers associated with the prognosis of patients with HPV-positive HNSCC.

Comparison of Hybribio-H13 and Hybrid Capture® 2 human papillomavirus tests for detection of CIN2+ and CIN3. / Comparación de las pruebas para el virus del papiloma humano Hybribio-H13 y Hybrid Capture® 2 para la detección de NIC2+ y NIC3+

INTRODUCTION: Low-cost, accurate high-risk HPV tests are needed for cervical cancer screening in limited-resource settings. OBJECTIVE: To compare the performance of the low-cost Hybribio-H13 test with the Hybrid Capture® 2 to detect cervical intraepithelial neoplasia grade 2 or 3 (CIN2 and CIN3). MATERIALS AND METHODS: Archived baseline samples tested by the Hybrid Capture® 2 from women of the ASCUS-COL trial, aged 20 to 69 years, with biopsy-colposcopy directed diagnosis of CIN2+ (n = 143), CIN3+ (n = 51), and < CIN2 (n = 632) were blindly tested by the Hybribio-H13 test. RESULTS: The relative sensitivity of the Hybribio-H13 test versus the Hybrid Capture® 2 for detecting CIN2+ was 0.89 (90% CI = 0,80-0,98; NIT = 0,66), and for CIN3+ was 0,92 (90% CI = 0,85-0,98; NIT = 0,35). Relative specificity was 1.19 (90% CI = 1.05-1.33; NIT <0.00001). In the analysis restricted to women older than 30 years, the relative sensitivity of the Hybribio-H13 for CIN3+ was marginally below unity (ratio = 0.97; 90% CI = 0.95-0.99), and the specificity remained higher than the Hybrid Capture® 2 test. CONCLUSION: The Hybribio-H13 test was as specific as the Hybrid Capture® 2 for detecting CIN2+ or CIN3+ but less sensitive. Considering these results and the young age of the population recruited for screening because of ASCUS cytology, we suggest our results warrant the evaluation of the Hybribio-H13 for screening cervical cancer, especially in the evaluated population.

Introducción. Se necesitan pruebas para detectar genotipos de VPH de alto riesgo, precisas y de bajo costo, para la tamización del cáncer de cuello uterino en entornos de recursos limitados. Objetivo. Comparar el desempeño de la prueba de bajo costo Hybrid-H13 con la de Hybrid Capture® 2 para detectar NIC2+ y NIC3+. Materiales y métodos. Se analizaron en ciego muestras de la línea base provenientes de mujeres del estudio ASCUS-COL, entre los 20 y los 69 años, con diagnóstico dirigido por biopsia-colposcopia de NIC2+ (n = 143), NIC3 + (n = 51) y < NIC2 (n = 632) con la prueba para detección de virus de papiloma humano Hybribio-H13. Estas muestras fueron previamente evaluadas con la prueba Hybrid Capture® 2. Resultados. La sensibilidad relativa de Hybribio-13 versus la de Hybrid Capture® 2 para detectar NIC2+ fue de 0,89 (IC90%: 0,80-0,98; NIT = 0,66) y para NIC3+ fue de 0,92 (IC90%: 0,85-0,98; NIT = 0,35). La especificidad relativa fue de 1,19 (IC90%: 1,05-1,33; NIT <0,00001). En el análisis restringido a mujeres mayores de 30 años, la sensibilidad relativa de Hybribio-H13 para NIC3+ estuvo marginalmente por debajo de la unidad (proporción = 0,97; IC90%: 0,95-0,99) y la especificidad permaneció más alta que la de la prueba Hybrid Capture® 2. Conclusión. La prueba de Hybribio-H13 fue tan específica como la de Hybrid Capture® 2, pero menos sensible para detectar NIC2+ o NIC3+. Teniendo en cuenta estos resultados y la temprana edad de la población reclutada en la tamización por la presencia de ASCUS en la citología, se sugiere continuar con la evaluación de la prueba Hybribio-H13 para la detección de cáncer de cuello uterino en poblaciones con las mismas características que las de la aquí evaluada.

Cervical Cancer in Mexico: From a Renowned Vaccination Program to Unfulfilled Needs in Treatment Access.

Mexico's national human papillomavirus (HPV) vaccination program was established in 2008, providing free access to HPV vaccines and quickly becoming an immense success story, achieving significant coverage among young Mexican females. However, despite these efforts and notable achievements, cervical cancer caused mainly by HPV remains a challenging issue among Mexican women aged 15 years or older. A critical obstacle faced by women in the country is a lack of early detection and screening resources, coupled with delays in diagnosis and treatment, exacerbated by the poor distribution of already insufficient healthcare resources. This situation creates adverse conditions for the female demographic in the country. Our editorial aims to draw attention to the urgent need to improve access to adequate prevention, screening, and treatment for cervical cancer patients in Mexico, advocating for a collective effort between the Mexican government, public health professionals, and civil society.

Multiple Messaging Strategies for Increasing HPV Vaccination Intentions among English- and Spanish-Speaking Parents in the United States and Mexico.

The reported study compared the impact of four influence strategies (agency assignment, enhanced active choice, deviance regulation marking, and temporal framing) on English- and Spanish-speaking parents' reported intention to vaccinate their children for HPV. An online experiment was conducted to examine the impact of the strategies. In a fractional factorial design, participating parents (N = 1663) were exposed to combinations of influence strategies in text messages presented as reminders they might receive from a healthcare provider about their child's eligibility for the vaccine series. The results indicated small but significant impacts of agency assignment, enhanced active choice, and deviance regulation marking on parents' reported vaccination intentions. The study adds to the research literature on HPV vaccination communication in two important respects. First, it demonstrated how incorporating evidence-based influence strategies into reminder messages can increase parents' vaccination intentions, an important precursor and predictor of actual vaccine uptake. Second, it sets an important precedent by examining the effects of influence strategies on vaccination intentions across different languages.

HPV Self-Sampling in the Workplace: A Qualitative Study of Benefits, Barriers, and Opportunities for Improvement Perceived by Health Professionals and Managers.

AIM: To inform the implementation of Human Papillomavirus Self-Sampling (HPV-SS) in the workplace, we assessed the perspectives of healthcare professionals and managers on the benefits, barriers, and opportunities for improvement of a pilot program. METHODS: A qualitative descriptive study based on in-depth telephone interviews was conducted between June and August 2023. Data were analyzed through inductive thematic analysis. Fifteen health professionals from different companies and fifteen managers from the Mexican Institute of Social Security (IMSS) were interviewed. RESULTS: Participants identified several benefits of the HPV-SS, including ease of use, privacy, convenience, affordability, reduced workplace absences, and promotion of a prevention culture. However, there were also individual and organizational barriers to program implementation. The former consisted of women's concerns about collecting a reliable sample or injuring themselves, lack of confidence in the HPV test, fear of positive results, and discomfort caused by the brush used to collect the sample. Organizational barriers included failure to follow up on positive test results, lack of knowledge of program indicators, perceived negative impact on the established Pap smear cervical cancer screening indicator, and the lack of government regulations supporting HPV testing. To improve the program, participants suggested disseminating information through mass media campaigns and social networks, providing companies with additional support from IMSS preventive staff, extending the work hours of IMSS Family Medicine clinics, and training IMSS health staff on the follow-up of women with HPV test results. CONCLUSIONS: The study findings suggest potential areas for improvement in HPV-SS programs.

Reconstructing Prehistoric Viral Genomes from Neanderthal Sequencing Data.

DNA viruses that produce persistent infections have been proposed as potential causes for the extinction of Neanderthals, and, therefore, the identification of viral genome remnants in Neanderthal sequence reads is an initial step to address this hypothesis. Here, as proof of concept, we searched for viral remnants in sequence reads of Neanderthal genome data by mapping to adenovirus, herpesvirus and papillomavirus, which are double-stranded DNA viruses that may establish lifelong latency and can produce persistent infections. The reconstructed ancient viral genomes of adenovirus, herpesvirus and papillomavirus revealed conserved segments, with nucleotide identity to extant viral genomes and variable regions in coding regions with substantial divergence to extant close relatives. Sequence reads mapped to extant viral genomes showed deamination patterns of ancient DNA, and these ancient viral genomes showed divergence consistent with the age of these samples (≈50,000 years) and viral evolutionary rates (10-5 to 10-8 substitutions/site/year). Analysis of random effects showed that the Neanderthal mapping to genomes of extant persistent viruses is above what is expected by random similarities of short reads. Also, negative control with a nonpersistent DNA virus does not yield statistically significant assemblies. This work demonstrates the feasibility of identifying viral genome remnants in archaeological samples with signal-to-noise assessment.

High frequency of alpha7-HPV in Colombian Caribbean coast women: cervical cancer screening analysis.

BACKGROUND: Cervical cancer (CC) is a significant global public health concern, particularly in developing countries such as Colombia. The main risk factor involves high-risk HPV types (HR-HPV) infection, coupled with population-specific variables. The Caribbean region in Colombia lacks research on HR-HPV-type frequencies. Therefore, this study aims to establish the prevalence of type-specific HR-HPV and its association with sociodemographic factors among women undergoing cervical cytology screening. METHODS: A cross-sectional study involving voluntary women who provided informed consent and completed a questionnaire capturing sociodemographic, clinical, and sexual behavior information was conducted. All participants underwent cervical cytology and molecular analysis. Generic HPV detection employed three simultaneous PCRs (GP5+/6+, MY09/11, and PU1R/2 M), and positive samples were genotyped using the Optiplex HPV Genotyping kit. The analysis encompassed the 12 types of high-risk HPV (HR-HPV-16,-18,-31,-33,-35,-39,-45,-51,-52,-56,-58, and - 59). Frequencies were reported based on geographic subregions within the Córdoba department, and disparities were made between single and multiple infections. Sociodemographic and clinical variables were subjected to ordinal logistic regression, with statistical significance at a p-value < 0.05. The statistical analyses utilized STATA 14® and R-Core Team-software. RESULTS: We included 450 women, mean age 40 (SD±11.44). PCR analysis revealed 43% HPV-positive (n=192). GP5+/6+ detected the most positives at 26% (n=119), followed by PU1R/2 M at 22% (n = 100) and MY09/11 at 15% (n=69). Multiple infections occurred in 87.3% (n=142), primarily 2 to 4 types (47.37%, n=90). Dominant types were HPV-18 (15.6%, n=61), HPV-16 (14.9%, n=58), HPV-31 (13.0%, n = 51), and HPV-45 (11.5%, n=45). Logistic regression identified age above 60 as a risk for concurrent multiple types (OR=6.10; 95% CI 1.18-31.63). Menopause was protective (OR=0.31; 95% CI 0.11-0.89). CONCLUSIONS: Our study reveals a notable prevalence of multiple (2-4) high-risk HPV infections among adult women engaged in CC detection initiatives. Predominantly, α7 species constitute the prevalent HR-viral types, with the Medio Sinú subregion showing elevated prevalence. Menopausal status confers protection against diverse HR-HPV infections. Nevertheless, advancing age, particularly beyond 60 years, is linked to an increased susceptibility to simultaneous infections by multiple HPV-types.