Assessing bias in the causal role of HPV in oral cancer: A systematic review and meta-analysis.

OBJECTIVE: High-risk human papillomaviruses (HPV) are an established cause of oropharyngeal cancer. Their relationship with oral cancer remains unclear with detection ranging from 0% to 100%. HPV DNA detection or evidence of exposure alone is insufficient to conclude causality. This systematic review assesses the extent of bias in studies of HPV detection in cancers of the oral cavity. METHODS: PubMed, Ovid MEDLINE, EMBASE, and PsycInfo databases were searched for observational studies reporting the effect of HPV in oral cavity specific cancers. RESULTS: All 15 included studies presented HPV DNA detection or serum HPV-antibodies, none included mRNA E6/E7 analysis. Cases with oral cancer had 5.36 times (95% CI 3.29-8.72) higher odds of having HPV detected compared to controls. The odds of HPV detection were higher in cell-based (OR 6.93; 95% CI 0.82-58.55) and tissue samples (OR 5.28; 95% CI 3.41-8.18) than blood-based samples (OR 3.36; 95% CI 1.53-7.40). CONCLUSION: When cancer site is clearly differentiated between oropharynx and oral cavity, 12 studies showed strong association between HPV and oral cancer, but the available estimates lack internal validity due to inconsistent measurements, high confounding, and lack of gold standard testing. There is not high-quality evidence to conclude a causal relationship of HPV with oral cancer.

Human papilloma virus (HPV)-related information acquisition and seeking behavior among infected women: A single center cross-sectional survey in Shanghai, China.

Lacking of adequate knowledge is an obstacle to effective prevention of cervical cancer, yet factors that affect the information acquisition and seeking behavior as well as the information communication process are not well studied. We assessed information acquisition and seeking behavior, as well as perceived barriers of doctor-patient communication regarding human papilloma virus (HPV)-related information of infected women. Among 437 participants, 405 (93%) expressed demands for HPV-related information, while only a small proportion (100/437, 22.9%) actively sought information and felt obstacles comprehending. Web-based channels were most frequently utilized and medical personnel were the most trusted information source. Patients' satisfaction was significantly correlated with doctor's patience (r = 0.581, p < 0.001) and emotional caring (r = 0.555, p < 0.001). Compared to patients not actively seeking information, those actively seeking information were more likely to be single (p = 0.005), had higher education (p = 0.009) and monthly individual-level income (p = 0.023), and was more likely to undergo regular cervical cancer screening (p = 0.003), and were already or willing to be vaccinated (p = 0.008). The actively seeking information group also achieved higher scores in HPV knowledge test (p = 0.007). Public health interventions targeting HPV-infected women using specifically designed educational materials may influence information seeking behavior, increase HPV literacy and knowledge, which could potentially increase HPV vaccine uptake and cervical cancer screening rate.

Knowledge About Cervical Cancer and Awareness About Human Papillomavirus Vaccination Among Medical Students at the Northern Border University, Arar, Kingdom of Saudi Arabia.

Objectives To evaluate the knowledge and awareness about cervical cancer and human papillomavirus (HPV) vaccination among medical undergraduates at Northern Border University. Methods It was a cross-sectional study done on students selected conveniently from the College of Medicine, Northern Border University, Arar. The data were collected regarding knowledge about HPV infection and vaccine awareness using a validated questionnaire. Results A total of 200 students responded to the questionnaires, with 104 (52%) being male students and 120 (60%) being clinical years of MBBS. The mean knowledge score was 17.12 ± 2.73 out of 24, which was labeled as moderate knowledge about cervical cancer and HPV. Almost two-thirds of the students responded correctly to the etiology and risk factors of cervical cancer, while only half of the students knew the correct screening intervals for cervical cancer. The awareness of students about the HPV vaccine was deficient, and the mean score was estimated to be 4.20 ± 0.79 out of nine. Female students and students in clinical years showed significantly better understanding and awareness about cervical cancer and its vaccine and showed greater vaccine acceptability as compared to male students and students in preclinical years. Conclusion The present study shows moderate knowledge about cervical cancer but deficient awareness of medical students about the HPV vaccine. However, the students were willing to get educated about cervical cancer and its vaccine and showed a favorable opinion towards vaccinating the schoolgirls and educating their patients as future physicians. The information can be considered a benchmark on knowledge and awareness levels and can be utilized to modify medical curricula and develop efficient awareness programs.

Human papillomavirus vaccination coverage among young women in the three sub-Saharan African countries using Demographic and Health Surveys data.

Cervical cancer is the fourth most common cancer, with 99% of cases linked to human papillomavirus (HPV) infection. It reflects global inequity as its burden is highest in low- and middle-income countries. The aim of this study was to determine the HPV vaccination coverage and its determinant factors among young women in the three sub-Saharan African countries. Data from the Demographic and Health Surveys among three sub-Saharan African countries were used for analysis. A total of 4,952 women were included in the study. Stata 14 was used to analyze the data. The determinants of the outcome variable were identified using a multilevel mixed-effects logistic regression model. Factors with p-values < 0.05 at 95% confidence interval were declared statistically significant. About 7.5% young women were vaccinated for HPV vaccine against cervical cancer in the current study. Younger age, use of internet, rich economic class, and individual-level media exposure were found to be favorable conditions, whereas being employed was negatively associated with HPV vaccination. Only few segments of young women in these three countries got HPV vaccination. The authors recommend that increasing internet use, media exposure, and economic level of young women will increase the HPV vaccination rates. Furthermore, creating awareness among employed women will also increase the possibility of HPV vaccination.

STEPS (Study To Examine Parent, Patient/Dental Provider Systems) to Prevent Human Papillomavirus (HPV)-Related Cancers: A Piloted Dental Patient and Provider Evaluation of Current and Future HPV Education.

Oropharyngeal human papillomavirus (HPV) cancers are prevalent, but HPV education in dental clinics is uncommon. The purpose of this study was to evaluate dental provider and patient knowledge from, attitudes towards, and preferences for HPV education, then assess perceptions of existing HPV educational materials for use at dental visits. Appalachian Ohio dental patients (n = 13) and general/pediatric dental providers (n = 10) completed an initial, close-ended survey on current HPV knowledge and HPV educational attitudes, participation, and resource preferences. Select individuals reviewed existing HPV educational videos and toolkits via virtual focus groups (n = 9) or independent review surveys (n = 6). Using a discussion guide, participants responded to overall, visual, auditory, and content satisfaction statements, orally (focus groups) or with Likert scales (independent reviews). Surveys were summarized with frequencies/percentages; transcripts were qualitatively coded to identify potential material modifications. Dental providers and patients were more comfortable with HPV and oral cancer education (87% and 96%, respectively) and screening (96%) than with HPV vaccine education (74%) and referrals (61%) during dental visits. Providers were neither sharing HPV educational materials (80%) nor initiating educational conversations with dental patients (100%). The American Cancer Society videos and the "Team Maureen" toolkit were the most liked resources (i.e., fewer negative/disagree statements) by all participant groups. Findings indicate that future dental HPV educational efforts should be informed by currently available materials. Additional interventions are needed to promote dental provider discussions and sharing of educational materials with patients to increase education and promotion of the HPV vaccine and reduce oropharyngeal cancers.

Emerging paradigms: unmasking the role of oxidative stress in HPV-induced carcinogenesis.

The contribution of the human papillomavirus (HPV) to cancer is significant but not exclusive, as carcinogenesis involves complex mechanisms, notably oxidative stress. Oxidative stress and HPV can independently cause genome instability and DNA damage, contributing to tumorigenesis. Oxidative stress-induced DNA damage, especially double-strand breaks, aids in the integration of HPV into the host genome and promotes the overexpression of two viral proteins, E6 and E7. Lifestyle factors, including diet, smoking, alcohol, and psychological stress, along with genetic and epigenetic modifications, and viral oncoproteins may influence oxidative stress, impacting the progression of HPV-related cancers. This review highlights various mechanisms in oxidative-induced HPV-mediated carcinogenesis, including altered mitochondrial morphology and function leading to elevated ROS levels, modulation of antioxidant enzymes like Superoxide Dismutase (SOD), Glutathione (GSH), and Glutathione Peroxidase (GPx), induction of chronic inflammatory environments, and activation of specific cell signaling pathways like the Phosphoinositide 3-kinase, Protein kinase B, Mammalian target of rapamycin (PI3K/AKT/mTOR) and the Extracellular signal-regulated kinase (ERK) signaling pathway. The study highlights the significance of comprehending and controlling oxidative stress in preventing and treating cancer. We suggested that incorporating dietary antioxidants and targeting cancer cells through mechanisms involving ROS could be potential interventions to mitigate the impact of oxidative stress on HPV-related malignancies.

Colposcopically Directed Biopsy Before Ablative Treatment Versus Direct Ablative Treatment in Patients With Cervical Oncogenic HPV.

Background/Aim: In the past, the standard of care for women with abnormal cervical cytology has been the performance of colposcopically guided biopsy, followed by conization or large loop excision of the transition zone (LLETZ) where biopsy revealed pre-cancerous or cancerous areas. More straightforward protocols are emerging which advocate performing LLETZ in all women with highly suspicious cytology, suspicious colposcopic impression, or the presence of high-risk oncogenic human papilloma virus (HPV) strains in their cervical swabs. This, theoretically, would reduce the rate of false-negative diagnoses, but at the price of overtreating a significant number of healthy women. Patients and Methods: We retrospectively analyzed cervical cancer screening protocols in two large cohorts of women with high-risk HPV. The study compared outcomes between patients undergoing a colposcopically directed biopsy before LLETZ (n=683) and those proceeding directly to LLETZ without a biopsy (n=136). The primary focus was to assess whether intervening biopsies would reduce unnecessary ablative procedures without compromising the detection of high-grade lesions. Results: The biopsy group had a high false-negative rate, with several high-grade lesions (CIN3) and a case of invasive cancer initially underdiagnosed. Conversely, the direct-to-LLETZ approach, while ensuring no high-grade lesions were missed, led to overtreatment of lower grade lesions. Conclusion: These findings raise concern about the reliance on biopsy results for treatment decisions. Neither protocol was entirely satisfactory, although the more aggressive one avoided the potentially life-threatening consequence of false-negative results. Further research is mandatory to accurately diagnose all cases requiring aggressive treatment, without subjecting healthy women to ablative treatments they do not need.

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.

Decoding dysregulated genes, molecular pathways and microRNAs involved in cervical cancer.

BACKGROUND: The present study aimed to identify dysregulated genes, molecular pathways, and regulatory mechanisms in human papillomavirus (HPV)-associated cervical cancers. We have investigated the disease-associated genes along with the Gene Ontology, survival prognosis, transcription factors and the microRNA (miRNA) that are involved in cervical carcinogenesis, enabling a deeper comprehension of cervical cancer linked to HPV. METHODS: We used 10 publicly accessible Gene Expression Omnibus (GEO) datasets to examine the patterns of gene expression in cervical cancer. Differentially expressed genes (DEGs), which showed a clear distinction between cervical cancer and healthy tissue samples, were analyzed using the GEO2R tool. Additional bioinformatic techniques were used to carry out pathway analysis and functional enrichment, as well as to analyze the connection between altered gene expression and HPV infection. RESULTS: In total, 48 DEGs were identified to be differentially expressed in cervical cancer tissues in comparison to healthy tissues. Among DEGs, CCND1, CCNA2 and SPP1 were the key dysregulated genes involved in HPV-associated cervical cancer. The five common miRNAs that were identified against these genes are miR-7-5p, miR-16-5p, miR-124-3p, miR-10b-5p and miR-27a-3p. The hub-DEGs targeted by miRNA hsa-miR-27a-3p are controlled by the common transcription factor SP1. CONCLUSIONS: The present study has identified DEGs involved in HPV-associated cervical cancer progression and the various molecular pathways and transcription factors regulating them. These findings have led to a better understanding of cervical cancer resulting in the development and identification of possible therapeutic and intervention targets, respectively.

Surgical treatment of perineal giant condylomata acuminata (Buschke Lowenstein tumor): Case series from a developing country.

INTRODUCTION: Giant condylomata acuminatum (GCA) also referred to as Buschke-Lowenstein tumor (BLT) is a rare tumor primarily associated with low-risk HPV 6 and 11, which is believed to be a slow growing intermediate tumor with low potential to transform into invasive cancer. CASE PRESENTATION: We presented our experience with three cases of BLT (one woman and two men). CLINICAL DISCUSSION: The three patients had surgical excision and two of them had reconstruction of the surgical defect with good clinical outcome. CONCLUSION: We highlighted the importance of early identification of symptoms, treatment options and risk of recurrence as well as primary preventive strategies.

Molecular Actions of Enicostemma hyssopifolium Whole Plant Extract on HPV18-Infected Human Cervical Cancer (HeLa) Cells.

OBJECTIVE: Enicostemma hyssopifolium (E. hyssopifolium) contains several bioactive compounds with anti-cancer activities. This study was performed to investigate the molecular effects of E. hyssopifolium on HPV18-containing HeLa cells. METHODS: The methanol extract of E. hyssopifolium whole plant was tested for cytotoxicity by MTT assay. A lower and higher dose (80 and 160 µg/mL) to IC50 were analyzed for colonization inhibition (Clonogenic assay), cell cycle arrest (FACS analysis), and induction of apoptosis (AO/EtBr staining fluorescent microscopy and FACS analysis) and DNA fragmentation (comet assay). The HPV 18 E6 gene expression in treated cells was analyzed using RT-PCR and qPCR. RESULTS: A significant dose-dependent anti-proliferative activity (IC50 - 108.25±2 µg/mL) and inhibition of colony formation cell line were observed using both treatments. Treatment with 80 µg/mL of extract was found to result in a higher percent of cell cycle arrest at G0/G1 and G2M phases with more early apoptosis, while 160 µg/mL resulted in more cell cycle arrest at SUBG0 and S phases with late apoptosis for control. The comet assay also demonstrated a highly significant increase in DNA fragmentation after treatment with 160 µg/mL of extract (tail moments-19.536 ± 17.8), while 80 µg/mL of extract treatment showed non-significant tail moment (8.152 ± 13.0) compared to control (8.038 ± 12.0). The RT-PCR and qPCR results showed a significant reduction in the expression of the HPV18 E6 gene in HeLa cells treated with 160 µg/mL of extract, while 80 µg/mL did not show a significant reduction. CONCLUSION: The 160 µg/mL methanol extract of E. hyssopifolium demonstrated highly significant anti-cancer molecular effects in HeLa cells.

The relationship between individuals' knowledge of human papillomavirus, attitudes towards HPV vaccination, and vaccine hesitancy: A cross-sectional study.

There are more than 207 types of Human Papillomavirus (HPV), most of which do not cause symptoms, lesions, or warts, and cause more than 600,000 cases of cancer annually. Purpose:This study was planned to elucidate the relationship between individuals' HPV knowledge, attitudes towards the HPV vaccine, and vaccine hesitancy. The research was conducted with 1011 people using a descriptive and correlational research design. Data collection tools included socio-demographic information survey, HPV Knowledge Scale, Carolina HPV Vaccination Attitudes Scale, and Vaccine Hesitancy Scale. The data was analyzed using the SPSS 26.0 package program. The average score was 11.68±7.23 on the HPV Knowledge Scale, 30.76±7.31 on the HPV Vaccine Attitude Scale, and 27.90±11.10 on the Vaccine Hesitancy Scale. While there was a very weak negative relationship between the participants HPV knowledge and HPV Vaccine Attitude scores, a weak positive relationship was found with vaccine hesitancy. A weak positive relationship was also detected between vaccine attitude and vaccine hesitancy (p<0.05). According to the regression model created in the study, HPV vaccination attitude was explained by the HPV Knowledge Scale and vaccine hesitancy at a rate of 22.5%. In line with the results, healthcare professionals need to raise awareness in the society and increase vaccination rates.

Il existe plus de 207 types de papillomavirus humain (HPV), dont la plupart ne causent pas de symptômes, de lésions ou de verrues, mais entraînent plus de 600 000 cas de cancer chaque année. Objectif : Cette étude a été planifiée pour élucider la relation entre les connaissances des individus sur le HPV, leurs attitudes envers le vaccin contre le HPV et l'hésitation vaccinale. La recherche a été menée auprès de 1011 personnes en utilisant un plan de recherche descriptif et corrélationnel. Les outils de collecte de données comprenaient un sondage d'informations sociodémographiques, l'Échelle de Connaissances sur le HPV, l'Échelle des Attitudes envers la Vaccination contre le HPV de la Caroline et l'Échelle d'Hésitation Vaccinale. Les données ont été analysées à l'aide du programme SPSS 26.0. Le score moyen était de 11,68 ± 7,23 à l'Échelle de Connaissances sur le HPV, de 30,76 ± 7,31 à l'Échelle des Attitudes envers la Vaccination contre le HPV, et de 27,90 ± 11,10 à l'Échelle d'Hésitation Vaccinale. Bien qu'il y ait eu une très faible relation négative entre les connaissances des participants sur le HPV et les scores d'attitude envers le vaccin contre le HPV, une faible relation positive a été trouvée avec l'hésitation vaccinale. Une faible relation positive a également été détectée entre l'attitude envers la vaccination et l'hésitation vaccinale (p<0,05). Selon le modèle de régression créé dans l'étude, l'attitude envers la vaccination contre le HPV était expliquée par l'Échelle de Connaissances sur le HPV et l'hésitation vaccinale à un taux de 22,5 %. Conformément aux résultats, les professionnels de la santé doivent sensibiliser la société et augmenter les taux de vaccination.

Estimation of self-funded human papillomavirus vaccine recipients from Japan's previously assumed "unvaccinated generation".

Precise vaccination data is essential to accurately estimate the effectiveness of the human papillomavirus (HPV) vaccine against HPV-related cancers. In Japan, the number of subsidized HPV vaccinations can be tracked through registries, but the number of self-funded vaccinations has not been tracked. The number of individuals who chose to receive the vaccine at their own expense, despite being ineligible for public subsidies due to their age, is unknown and has been nominally considered to be zero. Our aim is to produce a more accurate estimate of this number using recently released proprietary data. First, we estimated the total number of self-funded HPV vaccinations occurring from 2010 to 2012 using public data from the Ministry of Health, Labour and Welfare and our previously reported data on the number of HPV vaccinations eligible for public subsidy. Second, using proprietary data from the vaccine manufacturer, we calculated the distribution of self-funded vaccination shots by age. Finally, we combined these data to estimate the number of self-funded HPV vaccinations by birth fiscal year (FY) relative to a yearly reference population. We found that 78,264 individuals born in FY1993 and 58,190 born in FY1992 self-funded their vaccinations, representing 13.6% and 10.0% of the reference population, respectively. Additionally, we found that 5%-10% of individuals born from FY1986 to FY1991 self-funded their vaccinations. Our study revealed for the first time that a certain number of individuals from the "HPV unvaccinated generation," ineligible for subsidies due to age restrictions, chose to self-fund their vaccinations.

A transversal cross-sectional study of factors related to HPV vaccination status and cancer screening participation among French women aged 25-40.

BACKGROUND: In 2020, uterine cervical cancer (UCC) was the 12th most common cancer among women in France and the 4th worldwide. French health authorities wanted to increase Human Papilloma Virus (HPV) vaccination and screening rates. There were still many barriers to these measures among young women, their families, and health professionals and teachers. Between 2014 and 2019, international studies found inconsistent effects of HPV vaccination on UCC screening. In 2022, a survey was conducted among women aged 25 to 40 in the Nord-Pas-de-Calais region to assess participation 1) in HPV vaccination and its barriers, 2) in UCC screening as a function of HPV vaccination status. METHODS: Data were collected using an anonymous online questionnaire distributed by QR code in 80 general practices randomly selected in the Nord-Pas-de-Calais region between January and June 2022. Results were analyzed bivariately using the Chi2 test, multivariately when numbers allowed, and in age subgroups (sensitivity analysis). RESULTS: 407 complete questionnaires (for 602 participating women) were analyzed. In our sample, 41% of women aged 25 to 40 in the Nord-Pas-de-Calais region were vaccinated against HPV viruses in 2022. The risk factors for non-vaccination, after multivariable adjustment, were: the periods of eligibility for vaccination in the early days of French vaccination (2007-2012: odds ratio OR = 0.04 [95% CI, 0.02-0.09]; 2012-2017: OR = 0.5 [0.3-0.8]), information received from non-medical sources (OR = 0.3 [0.2-0.6]), and absence of information about vaccination (OR = 0.12 [0.05-0.27]). In our sample, 90% of women were screened for UCC. In bivariate analysis, women at risk of not being screened were those who were youngest, had been vaccinated against HPV, were not heterosexual, lived alone, had gynecological follow-up by their general practitioner, and did not have regular gynecological follow-up. Sensitivity analysis showed that the only risk factor significantly correlated with non-screening regardless of age group was lack of regular gynecological follow-up. CONCLUSIONS: Participation in HPV vaccination and UCC screening is improved by medical education and gynecological follow-up. This multicenter study, limited by the relative youth of vaccination in France, should be repeated after 2037 to assess the possible effect of vaccination on screening.

Coincidence or association: Adult-onset Still's disease following HPV vaccine.

This case details adult-onset Still's disease (AOSD) onset post-human papillomavirus (HPV) vaccination and acute gastroenteritis. The timing of HPV vaccine and vaccine-autoimmune disease literature may potentially confound the well-established link between infections and AOSD onset.

Comparison of preclinical efficacy of immunotherapies against HPV-induced cancers.

INTRODUCTION: Persistent infections with the human papilloma viruses, HPV16 and HPV18, are associated with multiple cancers. Although prophylactic vaccines that induce HPV-neutralizing antibodies are effective against primary infections, they have no effect on HPV-mediated malignancies against which there is no approved immuno-therapy. Active research is ongoing on immunotherapy of these cancers. AREAS COVERED: In this review, we compared the preclinical efficacy of vaccine platforms used to treat HPV-induced tumors in the standard model of mice grafted with TC-1 cells, which express the HPV16 E6 and E7 oncoproteins. We searched for the key words, 'HPV,' 'vaccine,' 'therapy,' 'E7,' 'tumor,' 'T cells' and 'mice' for the period from 2005 to 2023 in PubMed and found 330 publications. Among them, we selected the most relevant to extract preclinical antitumor results to enable cross-sectional comparison of their efficacy. EXPERT OPINION SECTION: We compared these studies for HPV antigen design, immunization regimen, immunogenicity, and antitumor effect, considering their drawbacks and advantages. Among all strategies used in murine models, certain adjuvanted proteins and viral vectors showed the strongest antitumor effects, with the use of lentiviral vectors being the only approach to result in complete tumor eradication in 100% of experimental individuals while providing the longest-lasting memory.

Persistent infections with the human papilloma virus HPV16 and HPV18 gentoypes can cause multiple cancers.Prophylactic anti-HPV vaccines show no efficacy against persistent HPV infections or already malignant tissues.No immunotherapy against HPV-induced cancers has been thus far approved for use in humans.Active research is ongoing on immunotherapy of HPV-induced malignancies.We compared the efficacy of the immunotherapy strategies developed against HPV-induced cancers in the standard murine TC-1 tumor model since 2005.Certain adjuvanted proteins and viral vectors induce the strongest effects against HPV-induced tumors.Lentiviral vectors, able to induce the longest-lasting T-cell immune memory, give rise to full eradication of large solid tumors in 100% of mice.

FRETting about CRISPR-Cas Assays: Dual-Channel Reporting Lowers Detection Limits and Times-to-Result.

Clustered Regularly Interspaced Short Palindromic Repeats-CRISPR-Associated Protein (CRISPR-Cas) systems have evolved several mechanisms to specifically target foreign DNA. These properties have made them attractive as biosensors. The primary drawback associated with contemporary CRISPR-Cas biosensors is their weak signaling capacity, which is typically compensated for by coupling the CRISPR-Cas systems to nucleic acid amplification. An alternative strategy to improve signaling capacity is to engineer the reporter, i.e., design new signal-generating substrates for Cas proteins. Unfortunately, due to their reliance on custom synthesis, most of these engineered reporter substrates are inaccessible to many researchers. Herein, we investigate a substrate based on a fluorescein (FAM)-tetramethylrhodamine (TAMRA) Förster resonant energy-transfer (FRET) pair that functions as a seamless "drop-in" replacement for existing reporters, without the need to change any other aspect of a CRISPR-Cas12a-based assay. The reporter is readily available and employs FRET to produce two signals upon cleavage by Cas12a. The use of both signals in a ratiometric manner provides for improved assay performance and a decreased time-to-result for several CRISPR-Cas12a assays when compared to a traditional FAM-Black Hole Quencher (BHQ) quench-based reporter. We comprehensively characterize this reporter to better understand the reasons for the improved signaling capacity and benchmark it against the current standard CRISPR-Cas reporter. Finally, to showcase the real-world utility of the reporter, we employ it in a Recombinase Polymerase Amplification (RPA)-CRISPR-Cas12a DNA Endonuclease-Targeted CRISPR Trans Reporter (DETECTR) assay to detect Human papillomavirus in patient-derived samples.

Assessing the long-term implications of age 9 initiation of HPV vaccination on series completion by age 13-15 in the US: projections from an age-structured vaccination model.

Introduction: Routine human papillomavirus (HPV) vaccination in the US is recommended at ages 11 or 12 years and can be given at age 9. Vaccination completion rates among adolescents 13-15 years in the US remain below the 80% goal. This study evaluated the long-term effects of increasing proactive HPV vaccination initiation rates at age 9 years in completion rates of adolescents. Methods: An age-structured vaccination model was developed and parametrized based on the National Immunization Survey-Teen (NIS-Teen) survey data. The model projected vaccination coverage (by vaccination status and age group), for 20 years, for a routine initiation scenario (no increase in initiation rates of 9-year-olds) and different proactive initiation (increased age 9 initiation) scenarios. The time to reach a completion rate of 80% for 13-15-year-olds was estimated. The model also generated projections stratified for subgroups of interest. Results: Results indicated that vaccine completion rates of 80% in 13-15-year-olds may not be achieved by 2040 under current trends of routine initiation at ages 11 or 12 years. However, increasing initiation rates in 9-year-olds by 1% and 3% annually could shorten the time to achieve 80% completion by 4 and 8 years, respectively. Stratification analyses showed that increasing initiation rates in 9-year-olds can also reduce disparities across subgroups in the time to achieve vaccination completion targets. Discussion: Increasing HPV vaccination initiation rates in 9-year-olds by as little as 1%-3% annually may be an effective strategy to improve HPV vaccination completion rates in adolescents by age 15 and reach the Healthy People goal of 80% completion much earlier.

Cervical Cancer and Its Association With Pregnancy.

Cancer is a disease in which abnormal cells divide uncontrollably, destroying tissues. A malignant tumor arises from cells in the cervix, the lower portion of the uterus (womb) that links the uterus to the vagina (birth canal), and is known as cervical cancer. One of the most significant global community health problems is cancer, which sees a daily increase in the number of sufferers. Therefore, it is crucial to expand our understanding of the molecular pathophysiology of cervical cancer and to suggest new therapeutic goals as well as new techniques for early detection of the illness. Since early diagnosis of pathologies can dramatically increase a patient's chance of survival, prognosis, and recurrence. This article aims to educate readers about some essential concepts surrounding cervical cancer, including the various types of cervical cancer, the stages of cancer, as well as their etiology, epidemiology, pathogenesis, management, and treatment, and its relationship with pregnancy. All of these concepts are essential for any individual studying medicine or working in the medical industry to understand. We intend to summarize the information that is currently available and the recommended courses of action for treating cervical cancer and its association with pregnancy in this review. Research priorities and controversies are also noted.

Metachronous Human Papillomavirus (HPV)-Related Eye Carcinoma in Previously Metastatic Breast Cancer: A Case Report.

Multiple primary malignancies (MPMs) occur when an individual develops two or more distinct primary cancers. These are categorized as synchronous or metachronous based on the timing of their diagnosis. Patients previously diagnosed with cancer face increased risks due to exposure to carcinogenic factors and treatments such as chemotherapy and radiotherapy. Individuals with a history of breast cancer are known to have elevated risks for secondary malignancies compared to the general population. However, cases of squamous cell carcinoma (SCC) of the eyelid in this group are exceedingly rare. Here, we present a case report describing a young female patient who sequentially developed metachronous breast cancer, and a human papillomavirus (HPV)-associated SCC of the eyelid. To the best of our knowledge, this case report represents the first documented instance of this specific combination of primary neoplasms in medical literature.