Comparative evaluation of HPV genotyping: A study on the performance concordance between Anyplex II HPV28 detection and Linear Array genotyping tests in nationwide studies in Brazil.

BACKGROUND: Advances in laboratory techniques for HPV diagnosis necessitate a thorough assessment of the efficiency, replicability, sensitivity, and specificity of those methods. This study aims to validate and compare HPV detection/genotyping using the Anyplex™ II HPV28 Detection assay (Seegene) assay and the Linear Array HPV Genotyping test (Roche Diagnostics) on genital samples for use in epidemiological studies. METHODS: From 6,388 penile and cervical DNA samples collected in the POP-Brazil, 1,745 were randomly selected to be included in this study. The samples were submitted to HPV detection and genotyping following the manufacturers' protocols. DNA was genotyped using the Anyplex™ II HPV28 Detection kit (Seegene), and the results were compared to those obtained using the Linear Array HPV Genotyping test (Roche Diagnostics). Concordance of HPV genotyping results was assessed by the percentage agreement and Cohen's kappa score (κ). RESULTS: The agreement between the two methodologies was deemed good for HPV detection (κ = 0.78). Notably, Anyplex™ II HPV28 demonstrated enhanced capability in detecting a broader spectrum of genotypes compared to Linear Array. CONCLUSION: Anyplex™ II HPV28 exhibited comparable results to the Linear Array assay in clinical specimens, showcasing its potential suitability for a diverse array of research applications requiring the detection and genotyping of HPV. The study supports the utility of Anyplex™ II HPV28 as an effective tool for HPV screening in epidemiological studies, emphasizing its robust performance in comparison to established diagnostic tests.

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.

Betapapillomavirus natural history and co-detection with alphapapillomavirus in cervical samples of adult women.

Human papillomaviruses (HPV) of the genus Betapapillomavirus can infect both cutaneous and mucosal sites, but research on their natural history at mucosal sites remains scarce. We examined the risk factors and co-detection patterns of HPVs of the Betapapillomavirus and Alphapapillomavirus genera in cervical samples of the Ludwig-McGill cohort study. We assessed a subset of 505 women from the Ludwig-McGill cohort study from São Paulo, Brazil. Cervical samples over the first year of follow-up were tested for DNA of over 40 alphapapillomavirus types and 43 betapapillomavirus types using a type-specific multiplex genotyping polymerase chain reaction assay. We assessed the risk factors for prevalent and incident betapapillomavirus type detection, and whether types were detected more frequently together than expected assuming independence using permutation tests, logistic regression, and Cox regression. We observed significant within-genus clustering but not cross-genus clustering. Multiple betapapillomavirus types were co-detected in the same sample 2.24 (95% confidence interval [CI]: 1.65-3.29) times more frequently than expected. Conversely, co-detections of alphapapillomavirus and betapapillomavirus types in the same sample occurred only 0.64 (95% CI: 0.51-0.83) times as often as expected under independence. In prospective analyses, positivity to one HPV genus was associated with a nonsignificant lower incidence of detection of types in the other genus. Lifetime number of sex partners and new sex partner acquisition were associated with lower risks of prevalent and incident betapapillomavirus detection. Betapapillomaviruses are commonly found in the cervicovaginal tract. Results suggest potentially different mechanisms of transmission for betapapillomavirus genital infections other than vaginal sex.

Lineage and phylogenetic analysis of HPV-16, -18 in saliva of HNSCC patients

Aim: Head and Neck Squamous Cell Carcinoma (HNSCC) is a global health problem whose incidence varies by geographic region and race according to risk factors. Human papillomavirus (HPV) infection is a significant risk factor for HNSCC. HPV-16 and HPV-18 are two forms of HPV that are carcinogenic. HNSCCs that are HPV positive have a better prognosis rather than HPV negative. The purpose of this research was to characterize HPV-16, -18 variations in the saliva of HNSCC patients by examining the genetic diversity of HPV-16, -18 utilizing the full E6, E7, and L1 genes. Methods:The case-control research included 15 patients with HNSCC and 15 healthy volunteers. Unstimulated entire saliva samples were obtained from the case and control groups by spitting method. Genomic DNA was isolated from all saliva samples. A PCR reaction was used to determine the presence of HPV in saliva. HPV-positive samples were genotyped and data were analyzed. We conducted a variant study on the HPV-16, -18 E6, and E7 genes. Results: Three patients with HNSCC were HPV-positive for two HPV genotypes out of 30 people diagnosed with HPV-DNA. HPV-16 and -18 were the most common genotypes. The HPV-16, -18 E6, and E7 genes were sequenced and compared to the HPV-16, -18 (E6, E7) prototype sequence. In all, HPV-16 lineages A1 and HPV-18 lineages A3 were discovered. Conclusion: Regarding the variation of HPV found in Iranian HNSCC patients, the need for further studies in HPV genotyping was seen. Sequencing HPV genes in HNSCC may help answer questions about HPV genotyping in the Iranian population. HPV genotype analysis aids in the development of vaccinations against HNSCC, halting disease progression and preventing HPV-associated HNSCC

Human papillomavirus genotyping using next generation sequencing (NGS) in cervical lesions: Genotypes by histologic grade and their relative proportion in multiple infections.

Sensitive and specific genotyping of human papillomaviruses (HPVs) is critical for the surveillance and monitoring of the vaccine effectiveness. Here, HPV genotypes were identified in 137 cervical samples with different histology (79 ≤CIN1 and 58 CIN3+) using Nested-PCR followed by Next-Generation sequencing (NGS) and relative proportions for each genotype in multiple infections were computed. All samples had been previously genotyped by PCR-Reverse Blotting Hybridization (PCR-RBH) thus allowing for a concordance analysis between both techniques. Multiple infections were present in 85% of ≤CIN1 cases compared to only 41% in CIN3+ cases (p<0.001). Among ≤CIN1 cases a towering genotypic diversity was observed, considering both low (LR-) and high risk (HR-) HPV genotypes; while among CIN3+, diversity was lower, HR-HPVs prevailing in most cases, especially HPV16. Furthermore, the predominance of HR-HPV genotypes in the proportions identified in each sample was higher in CIN3+ cases [(HPV16 (62.5%), followed by HPV31 and HPV58 (8.3% each)], than in ≤CIN1 cases [(HPV16 (17.7%), followed by HPV52 (14.7%) and HPV31 (10.3%)]. Agreement between PCR-RBH and NGS was higher than 90% for all genotypes (with an overall Kappa of 0.7), even though NGS identified eighty-nine positive results for HPV genotypes that had not been detected by PCR-RBH, evidencing its greater sensitivity. These results suggest that a reduction in genotypic diversity and/or an increase in the relative proportion of HR-HPVs in multiple infections can be considered as a biomarker for the potential risk of malignant progression.

Vaccination against human papillomavirus in Brazilian schoolchildren: National Survey of School Health, 2019.

OBJECTIVE: to analyze the prevalence of schoolchildren vaccinated against human papillomavirus (HPV) and the reasons related to non-vaccination. METHOD: cross-sectional study, with data from the 2019 National Survey of School Health. The sample consisted of 160,721 students aged 13 to 17 years. The prevalence and confidence intervals (95%CI) of vaccinated adolescents were estimated according to location, sex, and administrative dependence of the school. The differences between the strata were evaluated with the Chi-square test. Adjusted prevalence ratios (aPR) and 95%CI were estimated with the Poisson regression model. RESULTS: most of the students were vaccinated (62.9%), and the prevalence of girls (76.1%) was higher than that of boys (49.1%). The most prevalent reason for not vaccinating was "did not know they had to take" (46.8%), with the highest aPR in public schoolchildren in Brazil (1.6; 95%CI 1.5;1.7), from the Northeast region (1.2; 95%CI 1.1;1.2), and in students from private schools in the Northeast regions (1.1; 95%CI 1.1;1.2) and North (1.3; 95%CI 1.2;1.4). CONCLUSION: one out of every two Brazilian schoolchildren was vaccinated against HPV. Misinformation was a recurring reason for non-vaccination. The North and Northeast regions had the highest prevalence of non-vaccinated people, observed mainly in adolescents from public schools. HIGHLIGHTS: (1) 63% of Brazilian schoolchildren reported having been vaccinated against human papillomavirus (HPV).(2) In Brazil, in 2019, the prevalence of immunized girls was higher than that of boys.(3) Misinformation and fear are reasons for hesitating vaccination.(4) Social and health inequalities may reflect upon HPV vaccination.(5) Achieving the goal of 80% in HPV vaccination coverage is a challenge in Brazil.

Adolescents and young adults infected by the Human Papillomavirus (HPV): vulnerabilities and feelings experienced.

OBJECTIVE: To know the vulnerabilities experienced by adolescents and young adults infected by the Human Papillomavirus attended at a reference center in Feira de Santana - Bahia. METHOD: Qualitative study, carried out with a semi-structured interview with 20 adolescents and young adults, from November 2020 to February 2021. For data analysis, the Content Analysis proposed by Bardin and the software Iramuteq were used. RESULTS: The discovery of the infection highlights the misunderstanding about illness, fear, despair and guilt, individual and collective dimensions that point to little knowledge about the Human Papillomavirus. FINAL CONSIDERATIONS: It is necessary to implement public policies to minimize risks, through knowledge and confrontation of sexually transmitted infections, as well as health promotion strategies and shared decisions for the process of behavior change in adolescents and young adults.

Is there a higher frequency of anal dysplasia and infection by human papillomavirus in Crohn's disease patients?

The aim of this study was to compare the frequency of dysplasia and human papillomavirus (HPV) infection in the anal canal of patients with Crohn's disease (CD) with a control group and assess whether there is a correlation between use of immunosuppressants and anal manifestation of CD. Patients with CD and control individuals were submitted to anal cytology and material collection for polymerase chain reaction (PCR). The cytology was classified as normal, atypical squamous cells of undetermined significance (ASCUS), low-grade squamous intraepithelial lesion (LSIL), or high-grade (HSIL). PCR was considered positive or negative according to virus presence or absence. A total of 117 patients were included (54 in the control group and 63 in the CD group, being 32 without and 31 with immunosuppressants). ASCUS and LSIL were found in 25.9 and 22.2% of control patients and 28.6 and 39.7% of CD patients. HPV was identified in 14.8% of the control group and 27% of the CD group. In CD patients, HPV was found in 37.5 and 16.1% of those without and with immunosuppressants, respectively. Patients with perianal involvement had 15.6% of PCR positivity. There was no statistical difference in dysplasia and infection by HPV between the groups. Use of immunosuppressants did not influence the result, but anal manifestation was inversely proportional to viral detection.

Prevalence of oncogenic human papillomavirus in pregnant adolescents, association with colpocytological changes, risk factors and obstetric outcomes.

PURPOSE: The authors aim to carry out an investigation on the impact of cervical oncogenic Human Papillomavirus (HPV) detection in pregnant adolescents, to clarify the prevalence and risk factors, considering the importance and lack of data on this topic in Brazil. METHODS: A cross-sectional study was conducted with adolescents receiving prenatal care in a tertiary hospital in São Paulo, Brazil, with routine Pap smear and oncogenic HPV detection test in the uterine cervix. The authors sought to associate the results of these tests with demographic and obstetric variables. RESULTS: A total of 303 pregnant adolescents whose mean age was 15.30 ± 1.22 years comprised the study subjects. The frequency of high-risk HPV cervical detection was 50.50%. Multivariate analysis revealed that a large number of partners in their lifetime (OR = 1.27) and having a religion (OR = 2.05) were risk factors for cervical detection of oncogenic HPV, while schooling appeared as a protective factor (OR = 0.85). There was an association between this detection and colpocytological alterations, reaching almost 30% of patients, but without association with obstetric and neonatal outcomes. CONCLUSION: The prevalence found is one of the highest in Brazil and worldwide. A greater number of partners during their lifetime and having religion were detected as possible factors associated with cervical HPV detection. Detection of cervical HPV-DNA did not influence obstetric and neonatal outcomes. The findings of this study reinforce the need to implement educational measures capable of modifying the incidence of sexually transmitted infections in this population and capable of promoting adherence to HPV vaccination programs.

Ten Steps to Design a Counseling App to Reduce the Psychosocial Impact of Human Papillomavirus Testing on the Basis of a User-Centered Design Approach in a Low- and Middle-Income Setting.

PURPOSE: This study describes the 10 steps followed to produce the information architecture of a user-centered design (UCD) counseling mobile application, the first phase to develop an app. The app aims to reduce the psychosocial impact of the human papillomavirus test result and improve women's knowledge of human papilloma virus and cervical cancer. METHODS: We used a UCD approach to produce the information architecture of the app (ie, how to organize contents into features). We analyzed field notes, meeting agendas, and documentation produced during each stage of the design process. We described the goals, methods, and outcomes of each step. We also discussed the critical challenges and the strategies to address them. RESULTS: The steps are (1) knowledge, attitudes, and beliefs mapping: reanalysis of team's research findings from prior studies; (2) environmental scanning of apps available on the market; (3) stakeholders' point of view: The International Advisory Committee; (4) potential user's profile: building archetypes through the Persona method; (5) women's interviews: user's preferences and experiences; (6) effective features: scoping review to select app's features that address psychosocial impact; (7) the user journey: ideal interaction with the gynecological service and the counseling app; (8) women's focus groups: using Personas and Scenarios to discuss app's mock-up; (9) women's design sessions: prototype test and card-sorting techniques; and (10) team's design session: translating results into visual objects and features. CONCLUSION: We provide here detailed descriptions of the UCD process of an app for human papillomavirus-tested women for those venturing into the area of mHealth strategies work. Our experience can be used as a guide for future mHealth app development for a low- and middle-income setting.

Human Papillomavirus Modulates Matrix Metalloproteinases During Carcinogenesis: Clinical Significance and Role of Viral Oncoproteins.

Human papillomavirus (HPV) infections are associated with cervical cancer and other anogenital cancers. Despite progresses in HPV vaccination and screening, these cancers still show high incidence and mortality, requiring improved prognostic markers and tailored therapies. This review addresses the role of Matrix metalloproteinases (MMPs) in HPV-induced cancers and the modulation of MMP expression by HPV oncoproteins. Scientific literature indexed in PubMed and ScienceDirect about Human papillomavirus modulates matrix metalloproteinases was retrieved and critically analyzed, to obtain an overview of expression patterns and their implications for carcinogenesis and patient prognosis. Matrix metalloproteinases such as MMP1, MMP9 and MMP13 have been associated with patient prognosis in HPV-induced cancers and play a major role in the degradation of the extracellular matrix, tumor invasion and metastasis. The HPV E2 and E7 oncoproteins regulate MMP expression via AKT, MEK/ERK and AP-1 signaling among other mechanisms. Increased expression of MMPs is associated with cancer progression and poor prognosis in multiple HPV-induced cancers, suggesting their potential use as prognostic markers. The identification of specific signaling pathways that mediate MMP regulation by HPV is essential for developing efficient new cancer therapies.

HPV infection and 5mC/5hmC epigenetic markers in penile squamous cell carcinoma: new insights into prognostics.

BACKGROUND: Penile cancer is one of the most aggressive male tumors. Although it is preventable, the main etiologic causes are lifestyle behaviors and viral infection, such as human papillomavirus (HPV). Long-term epigenetic changes due to environmental factors change cell fate and promote carcinogenesis, being an important marker of prognosis. We evaluated epidemiological aspects of penile squamous cell carcinoma (SCC) and the prevalence of HPV infection using high-risk HPV (hrHPV) and p16INK4A expression of 224 participants. Global DNA methylation was evaluated through 5-methylcytosine (5mC) and 5-hydroxymethylcytosine (5hmC). RESULTS: The incidence of HPV was 53.2% for hrHPV and 22.32% for p16INK4a. hrHPV was not related to systemic or lymph node metastasis and locoregional recurrence, nor influenced the survival rate. P16INK4a seems to be a protective factor for death, which does not affect metastasis or tumor recurrence. Lymph node and systemic metastases and locoregional recurrence increase the risk of death. An increased 5mC mark was observed in penile SCC regardless of HPV infection. However, there is a reduction of the 5hmC mark for p16INK4a + (P = 0.024). Increased 5mC/5hmC ratio (> 1) was observed in 94.2% of penile SCC, irrespective of HPV infection. Despite the increase in 5mC, it seems not to affect the survival rate (HR = 1.06; 95% CI 0.33-3.38). CONCLUSIONS: P16INK4a seems to be a good prognosis marker for penile SCC and the increase in 5mC, an epigenetic mark of genomic stability, may support tumor progression leading to poor prognosis.

Association strength of E6 to E6AP/p53 complex correlates with HPV-mediated oncogenesis risk.

Human papillomavirus (HPV) is recognized as the causative agent of cervical cancer in women, and it is associated with other anogenital and head/neck cancers. More than 120 types of HPV have been identified and many classified as high- or low-risk according to their oncogenic potential. One of its proteins, E6, has evolved to overcome the oncosuppressor functions of p53 by targeting this protein for degradation via interaction with the human ubiquitin-ligase E6AP. This study evaluates the correlation between the association strength of 40 HPV E6 types to the E6AP/p53 complex and the HPV oncogenesis risk using molecular simulations and machine and deep learning (ML/DL). In addition, a ML/DL-driven prediction is proposed for the HPV unclassified oncogenic risk type. The results indicate that thermodynamics play a pivotal role in the establishment of HPV-associated cancer and highlight the need to include some viral types in the HPV-related cancer surveillance and prevention strategies.

Modeling and Mathematical Analysis of the Dynamics of HPV in Cervical Epithelial Cells: Transient, Acute, Latency, and Chronic Infections.

The aim of this paper is to model the dynamics of the human papillomavirus (HPV) in cervical epithelial cells. We developed a mathematical model of the epithelial cellular dynamics of the stratified epithelium of three (basale, intermedium, and corneum) stratums that is based on three ordinary differential equations. We determine the biological condition for the existence of the epithelial cell homeostasis equilibrium, and we obtain the necessary and sufficient conditions for its global stability using the method of Lyapunov functions and a theorem on limiting systems. We have also developed a mathematical model based on seven ordinary differential equations that describes the dynamics of HPV infection. We calculated the basic reproductive number (R 0) of the infection using the next-generation operator method. We determine the existence and the local stability of the equilibrium point of the cellular homeostasis of the epithelium. We then give a sufficient condition for the global asymptotic stability of the epithelial cell homeostasis equilibrium using the Lyapunov function method. We proved that this equilibrium point is nonhyperbolic when R 0 = 1 and that in this case, the system presents a forward bifurcation, which shows the existence of an infected equilibrium point when R 0 > 1. We also study the solutions numerically (i.e., viral kinetic in silico) when R 0 > 1. Finally, local sensitivity index was calculated to assess the influence of different parameters on basic reproductive number. Our model reproduces the transient, acute, latent, and chronic infections that have been reported in studies of the natural history of HPV.

University Students' Knowledge about the Relation between Human Papillomavirus (HPV) and Head and Neck and Oral Cancers.

INTRODUCTION: Human papillomavirus (HPV) causes the most common sexually transmitted infection (STI) in the world. It affects people regardless of gender and age, causing genital warts and cancer. OBJECTIVE: To evaluate university students' knowledge of HPV and its relationship with head and neck and oral cancers. METHODS: This is a cross-sectional study using an online questionnaire administered to undergraduate students at a public university (n=335). RESULTS: In total, 69.3% of the participants were unaware of the relationship between HPV and head and neck cancers and 34.6% claimed that HPV may not cause oral cancer.  The chances of knowing about the relationship of HPV with head and neck cancers were significant for participants who knew that HPV could be asymptomatic (OR = 9.9; p = 0.029), that might cause genital warts in men (OR = 4.0; p = 0.015), and those aged 24 years or older (OR = 1.9; p = 0.021). However, undergraduate students in the field of health and medicine (OR = 0.419; p = 0.002), who had sex at least twice a week (OR = 0.471; p = 0.017), and were unaware of the target public for the HPV vaccine (OR: 0.222, p<0.001) were less likely to know about the relationship. Students who knew of the relationship between HPV and female (OR = 3.6; p = 0.010) and male genital warts (OR = 3.0; p = 0.005) or were immunized (OR = 1.8; p = 0.020) were more likely to understand the viral interaction with oral cancer. Those who were unaware of the population eligible for HPV vaccine (OR = 0.493; p = 0.017) also showed gaps in their knowledge of this relationship. CONCLUSION: Our findings showed that there were limitations in the knowledge about HPV, its vaccine, and its relationship with head and neck and oral cancers.

Epidemiology and Molecular Biology of HPV Variants in Cervical Cancer: The State of the Art in Mexico.

Cervical cancer (CC) continues to be a major public health problem in Mexico, ranking second among cancers in women. A persistent infection with human papillomaviruses (HPV) is the main risk factor for CC development. In addition, a significant fraction of other cancers including those of the anus, oropharynx, and penis are also related to HPV infection. In CC, HPV-16 is the most prevalent high-risk HPV type, followed by HPV-18, both being responsible for 70% of cases. HPV intratype variant lineages differ in nucleotide sequences by 1-10%, while sublineages differ by 0.5-1%. Several studies have postulated that the nucleotide changes that occur between HPV intratype variants are reflected in functional differences and in pathogenicity. Moreover, it has been demonstrated that HPV-16 and -18 intratype variants differentially affect molecular processes in infected cells, changing their biological behavior that finally impacts in the clinical outcome of patients. Mexico has participated in providing knowledge on the geographical distribution of intratype variants of the most prevalent HPVs in premalignant lesions of the cervix and cervical cancer, as well as in other HPV-related tumors. In addition, functional studies have been carried out to assess the cellular effects of intratype variations in HPV proteins. This review addresses the state of the art on the epidemiology of HPV-16 and HPV-18 intratype variants in the Mexican population, as well as their association with persistence, precancer and cervical cancer, and functional aspects related to their biological behavior.

CIGB-300 Peptide Targets the CK2 Phospho-Acceptor Domain on Human Papillomavirus E7 and Disrupts the Retinoblastoma (RB) Complex in Cervical Cancer Cells.

CIGB-300 is a clinical-grade anti-Protein Kinase CK2 peptide, binding both its substrate's phospho-acceptor site and the CK2α catalytic subunit. The cyclic p15 inhibitory domain of CIGB-300 was initially selected in a phage display library screen for its ability to bind the CK2 phospho-acceptor domain ofHPV-16 E7. However, the actual role of this targeting in CIGB-300 antitumoral mechanism remains unexplored. Here, we investigated the physical interaction of CIGB-300 with HPV-E7 and its impact on CK2-mediated phosphorylation. Hence, we studied the relevance of targeting E7 phosphorylation for the cytotoxic effect induced by CIGB-300. Finally, co-immunoprecipitation experiments followed by western blotting were performed to study the impact of the peptide on the E7-pRB interaction. Interestingly, we found a clear binding of CIGB-300 to the N terminal region of E7 proteins of the HPV-16 type. Accordingly, the in vivo physical interaction of the peptide with HPV-16 E7 reduced CK2-mediated phosphorylation of E7, as well as its binding to the tumor suppressor pRB. However, the targeting of E7 phosphorylation by CIGB-300 seemed to be dispensable for the induction of cell death in HPV-18 cervical cancer-derived C4-1 cells. These findings unveil novel molecular clues to the means by which CIGB-300 triggers cell death in cervical cancer cells.

Association of human papillomavirus vaccination with cervical cancer screening: A systematic review and meta-analysis.

INTRODUCTION: Prophylactic vaccination and routine screening are effective at preventing most cases of cervical cancer. Globally, cervical cancer is the fourth most frequently diagnosed cancer among women. The aim of this study was to investigate the association between human papillomavirus virus (HPV) vaccination (1, 2, or 3 doses) and cervical cancer screening. METHODS: PubMed (MEDLINE), Scopus, Web of Science, and Cochrane Library electronic databases were systematically searched from July 1, 2006, up to September 30, 2021. We pooled estimates using random-effects models. Heterogeneity between studies was quantified using Cochran Q test and I2 statistics. In total, 12 studies involving 2.4 million individuals were included in the meta-analysis. RESULTS: In the adjusted estimates, uptake of HPV vaccination was associated with increased cervical cancer screening (pooled relative risk [RR]: 1.35; 95% confidence interval [CI]: 1.21, 1.50; n = 12). Between-study heterogeneity was large (I2 = 99%). Compared to unvaccinated, those who received 3 doses of HPV vaccine had the highest uptake of cervical cancer screening (RR: 1.85; 95% CI: 1.58, 2.17), followed by those who received 2 doses (RR: 1.34; 95% CI: 1.21, 1.47). No statistically significant association with screening was found for those who received a single dose of the HPV vaccine. CONCLUSION: In this meta-analysis, uptake of HPV vaccination was associated with higher cervical cancer screening. It is plausible that vaccinated individuals are more likely to engage in preventive health behaviors. Healthcare providers should remind patients to continue with routine screening for cervical cancer regardless of their HPV vaccine status since vaccination does not protect against all HPV types.