High-risk Strains Of Human Papillomavirus Research Articles

Prevalence and genotype distribution of potential high-risk and high-risk human papillomavirus among women attending selected reproductive health clinics in lake victoria basin-kenya: a cross-sectional study

BackgroundPersistent human papillomavirus (HPV) infection is considered the primary etiological factor for invasive cervical cancer. Understanding the epidemiology of circulating potential high-risk (HR) and HR HPV strains is essential in updating epidemiological knowledge and recommendations on genotype-specific vaccination development. This study determined the prevalence and factors associated with Potential HR/HR HPV among women attending selected reproductive health clinics in Lake Victoria Basin.MethodsA cross-sectional facility-based survey made up of 434 women aged 16–68 years was carried out in two selected facilities. Structured questionnaires were administered to collect participant clinical and social characteristics. Cervical specimens were collected and HPV genotyping was carried out using RIATOL HPV genotyping qPCR assay. Descriptive statistics followed by logistic binary regression was done using R version 4.3.2.ResultsThe overall prevalence of potential HR/HR HPV among women attending the selected reproductive health clinics was reported at 36.5% (158/434). Specifically, in the rural setting, Gobei Health Center, the prevalence was 41.4% (41/99) while in the urban setting-JOOTRH, it was 34.6% (117/335). The most prevalent potential HR/HR HPV are 52, 67, 16, 31, 39, 45, and 31 among women. Age was the main factor associated with HPV infection with women between the age of 30–39 having the highest risk (AOR = 0.3, CI:0.2–0.7, p < 0.001).ConclusionIn both rural and urban regions, potential HR/HR HPV infection among women attending reproductive health clinics at the selected facilities remains common. The study identifies the need for effective implementation and clinical follow-up process of cervical cancer control program in the LVB.

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.

Trends in human papilloma virus vaccination uptake by sex and race/ethnicity among US adolescents and young adults, 2011-2020.

10519 Background: High-risk strains of human papillomavirus (HPV) are associated with a variety of oral and anogenital cancers, many of which are preventable through HPV vaccination. In the US, completion of an HPV vaccination series is recommended for all individuals from age 9 through 26; however, national trends in HPV vaccination uptake across sex and racial/ethnic groups over the past decade are not well described. Methods: We analyzed data from the National Health and Nutrition Examination Survey across 4 survey cycles spanning January 2011 to March 2020. We used univariate logistic regression to evaluate temporal trends in HPV vaccination uptake across sex and racial/ethnic strata, with the midpoint of each survey cycle modeled as a continuous independent variable. Vaccination uptake was defined as self/parent-reported receipt of ≥ 1 dose of an HPV vaccine series (estimates for 2 and 3 doses were unreliable due to recall bias and missing data). All estimates incorporated appropriate survey weights to be representative of the US population. Results: We identified 10,927 participants representing 70,066,252 individuals: mean age 17.4 years, 48.8% male, 54.9% White. Between 2011-March 2020, overall HPV vaccination uptake steadily increased from 23.3% to 43.0% ( P trend &lt; 0.001; Table). HPV vaccination rates improved from 37.7% to 49.4% among females ( P trend &lt; 0.001) and from 7.8% to 36.4% among males ( P trend &lt; 0.001). HPV vaccination uptake increased similarly across all racial/ethnic strata by approximately 20%, with White individuals achieving the greatest vaccination uptake (45.5%) by March 2020. Conclusions: Among US adolescents and young adults, HPV vaccination uptake rose by ~20% overall and across all racial/ethnic groups. HPV vaccination uptake accelerated the most among males but still lags behind females, perhaps because routine vaccination wasn’t recommended for males until 2011, 5 years after it had been recommended for females. [Table: see text]

Knowledge on Human Papillomavirus Infections, Cancer Biology, Immune Interactions, Vaccination Coverage and Common Treatments: A Comprehensive Review.

Human papillomavirus (HPV) is a circular, double-stranded DNA virus and recognized as the most prevalent sexually transmitted infectious agent worldwide. The HPV life cycle encompasses three primary stages. First, the virus infiltrates the basal cells of the stratified epidermis. Second, there is a low-level expression of viral genes and preservation of the viral genome in the basal layer. Lastly, productive replication of HPV occurs in differentiated cells. An effective immune response, involving various immune cells, including innate immunity, keratinocytes, dendritic cells, and natural killer T cells, is instrumental in clearing HPV infection and thwarting the development of HPV-associated tumors. Vaccines have demonstrated their efficacy in preventing genital warts, high-grade precancerous lesions, and cancers in females. In males, the vaccines can also aid in preventing genital warts, anal precancerous lesions, and cancer. This comprehensive review aims to provide a thorough and detailed exploration of HPV infections, delving into its genetic characteristics, life cycle, pathogenesis, and the role of high-risk and low-risk HPV strains. In addition, this review seeks to elucidate the intricate immune interactions that govern HPV infections, spanning from innate immunity to adaptive immune responses, as well as examining the evasion mechanisms used by the virus. Furthermore, the article discusses the current landscape of HPV vaccines and common treatments, contributing to a holistic understanding of HPV and its associated diseases.

Saliva-based detection of oral HPV and oral cancer.

6057 Background: Head and neck cancers (HNC) consist of a group of biologically and clinically diverse malignancies. Oral cavity squamous cell carcinoma (OCSCC) and oropharyngeal squamous cell carcinoma (OPSCC) are the most common subtypes, together comprising the majority of HNC cases. While these cancers are associated with tobacco use and alcohol consumption, infection with human papilloma virus (HPV) is also etiologic to HNC, with OPSCC known to harbor higher HPV positivity (HPV+) rates relative to OCSCC, which is largely HPV-negative (HPV-). This distinction is clinically relevant as HPV+ tumors are more responsive to therapy and associated with better prognosis. While early-stage OCSCC/OPSCC has 5-year survival rates of &gt;80%, diagnosis typically occurs at advanced stages, where the survival rate drops to 20-40%. Compounding this grim outlook is the growing incidence in patients that do not smoke or drink alcohol, as well as the startling rise in HPV+ OPSCC cases, thus increasing the affected population and burden on the healthcare system. Currently, painful incisional biopsies are the standard method to diagnose HNC, and there are no accepted non-invasive screening options for early disease detection or serial assessment of treatment efficacy. There is an urgent need for non-invasive diagnostic solutions that accurately identify disease at an early stage and quickly discern HPV status to inform effective treatment decisions and improve patient outcomes. Methods: We have recently developed a novel salivary liquid biopsy screening method for early detection of OCSCC, which relies on targeted NGS of 7 commonly mutated genes associated with OCSCC tumorigenesis, and shown that it is able to accurately and reproducibly identify ~93% of patients with OCSCC, including early stage cases. To enhance the capabilities of this screening platform we have incorporated probes targeting high-risk HPV strains (hrHPV16/18) into the sequencing panel. Results: Applying this multi-functional assay to a cohort of 20 primary OCSCC tumors, driving somatic mutations were detected in all cases. Furthermore, using the 5% alignment cutoff, all OCSCC specimens were HPV-. We next sequenced HPV+ OPSCCs using the same criteria, detecting 93% of the cases as HPV positive by our combined assay. We next applied this updated assay to saliva specimens collected from 30 OCSCC patients and 10 healthy individuals. Somatic mutations were detected in all OCSCC saliva specimens, while no actionable aberrations were found in healthy controls. As expected, 27 of 30 OCSCC saliva samples were HPV-, with the remaining 3 samples being inconclusive. Conclusions: While additional validation is needed to accurately assess the performance of this dual panel in saliva specimens, such multi-functional (mutational drivers/HPV) detection assay may facilitate personalized treatment decisions based on tumor biology (mutations) in addition to clinical risk factors (presence of hrHPV).

Structure-Based Discovery of Potential HPV E6 and EBNA1 Inhibitors: Implications for Cervical Cancer Treatment

Cervical cancer is the fourth most diagnosed cancer and the fourth leading cause of cancer death in women globally. Its onset and progression have been attributed to high-risk human papillomavirus (HPV) types, especially 16 and 18, while the Epstein–Barr virus (EBV) is believed to also significantly contribute to cervical cancer growth. The E6 protein associated with high-risk HPV strains, such as HPV16 and HPV18, is known for its role in promoting cervical cancer and other anogenital cancers. E6 proteins contribute to the malignant transformation of infected cells by targeting and degrading tumor suppressor proteins, especially p53. On the other hand, EBV nuclear antigen 1 (EBNA1) plays a crucial role in the maintenance and replication of the EBV genome in infected cells. EBNA1 is believed to increase HPV E6 and E7 levels, as well as c-MYC, and BIRC5 cellular genes in the HeLa cell line, implying that HPV/EBV co-infection accelerates cervical cancer onset and growth. Thus, the E6 and EBNA1 antigens of HPV and EBV, respectively, are attractive targets for cervical cancer immunotherapy. This study, therefore, virtually screened for potential drug candidates with good binding affinity to all three oncoviral proteins, HPV16 E6, HPV18 E6, and EBNA1. The compounds were further subjected to ADMET profiling, biological activity predictions, molecular dynamics (MD) simulations, and molecular mechanics Poisson–Boltzmann surface area (MM/PBSA) calculations. A total of six compounds comprising ZINC000013380012, ZINC000070454124, ZINC000014588133, ZINC000085568136, ZINC000095909247, and ZINC000085597263 demonstrated very strong affinity (≤−60 kJ/mol) to the three oncoviral proteins (EBNA1, HPV16 E6, and HPV18 E6) after being subjected to docking, MD, and MM/PBSA. These compounds demonstrated relatively stronger binding than the controls used, inhibitors of EBNA1 (VK-1727) and HPV E6 (baicalein and gossypetin). Biological activity predictions also corroborated their antineoplastic, p53-enhancing, Pin1 inhibitory, and JAK2 inhibitory activities. Further experimental testing is required to validate the ability of the shortlisted compounds to silence the insidious effects of HPV E6 and EBNA1 proteins in cervical cancers.

Interobserver reproducibility of cervical histology interpretation with and without p16 immunohistochemistry.

Histopathological diagnosis of colposcopically identified cervical lesions is a critical step for the recognition of cervical cancer precursors requiring treatment. Although there have been efforts to standardize the histologic diagnosis of cervical biopsy specimens, in terms of terminology and use of biomarkers, there is no uniform approach in the pathology community. Adjunctive p16 immunohistochemistry (IHC) can highlight precancer diagnoses, with use recommendations outlined by the Lower Anogenital Squamous Terminology project. We assessed the diagnostic reproducibility of cervical histopathological biopsy specimens with and without p16 staining among 2 expert pathologists. Interpretation of p16 IHC as positive vs negative was highly reproducible (92.5% agreement, κ = 0.85); greater variation was seen in the choice of which biopsy specimens required adjunctive p16 staining (78.0% agreement, κ = 0.43). Adjunctive p16 IHC did not significantly increase diagnostic agreement under multitiered grading systems (benign vs cervical intraepithelial neoplasia [CIN] 1/low-grade squamous intraepithelial lesion vs atypical squamous metaplasia vs CIN2/high-grade squamous intraepithelial lesion [HSIL] vs CIN3/HSIL-CIN3 vs cancer) (65.5% agreement, κ = 0.56 without p16; 70.0% agreement, κ = 0.58 with p16). However, when dichotomizing diagnoses based on clinical management (less than HSIL vs HSIL+), diagnostic agreement increased with p16 IHC (90.5% agreement, κ = 0.79 without p16; 92.0% agreement, κ = 0.84 with p16). For biopsy specimens taken from women positive for human papillomavirus (HPV) type 16, agreement was similar with or without adjunctive p16 (κ = 0.80 without p16; κ = 0.78-0.80 with p16). In contrast, p16 IHC substantially improved diagnostic agreement for cervical biopsy specimens taken from women positive for other high-risk HPV strains, producing improvements in κ from 0.03 to 0.24. Adjunctive p16 immunostaining provides useful information in the evaluation of cervical biopsies for precancer. In our study, we have demonstrated that it is highly reproducible between 2 pathologists, although the decision of which biopsies warrant its use is less so. Furthermore, although p16 IHC showed a limited increase in diagnostic reproducibility for all biopsies included in our study, it did demonstrate a more sizable gain in biopsies negative for HPV 16 but positive for other high-risk genotypes. Further studies are needed to clarify the role of p16 IHC and how it can be optimized for the detection of cervical precancer, particularly in HPV-vaccinated populations where types other than HPV 16 are relatively more important.

Therapeutic Effect Analysis of Cervical Cancer Vaccine

Cervical cancer is a very widespread carcinogenic condition that poses a significant threat to women's health. The primary cause of this condition is mostly linked to persistent infection with high-risk strains of human papillomavirus (HPV), which are recognized for their ability to promote the development of cancer. Due to HPV infection, both therapeutic and preventative HPV vaccinations have been developed. Therapeutic vaccines can eradicate viruses and virus-infected cells by stimulating cellular immunity. Notwithstanding the availability of preventive HPV vaccinations, HPV screening, surgery, radiotherapy, and chemotherapy, the therapeutic effect on cervical cancer patients is limited. Therefore, therapeutic vaccines have emerged as a new treatment option. The cancer-causing proteins E6 and E7, which are consistently detected in cervical cancer and precancerous lesions, are crucial in the progression and sustenance of cervical cancer. Consequently, these cancer-causing proteins present an encouraging opportunity for the research and creation of therapeutic cervical cancer vaccines. The multiple therapeutic vaccines against cervical cancer will be briefly discussed in this article, including their mechanisms, development methods, and clinical effects.

Abstract 2141: Prevalence of cervical high risk HPV serotypes not covered by the 9vt vaccine in a clinic-based sample of Hispanic women living in Puerto Rico

Abstract Cervical cancer (CC) is the fourth most common female malignancy worldwide. Puerto Rico (PR) has the highest age-adjusted incidence of cervical cancer in the U.S. High-risk strains of human papillomavirus (hr-HPV) have been identified as common causative agents of CC. We aimed to characterize the prevalence of High-Risk HPV (HR-HPV) genotypes among a clinic-based sample of 368 HIV-negative women using a high-resolution approach. We used baseline data from IRB protocol 10510114. Cervical swabs underwent genomic DNA extractions followed by typification of HPV genotypes using a short-polymerase chain reaction-fragment assay (SPF10-LiPA) which detects 14 mucosal HR-HPV types (LiPA-25); 10 types (8 HR and 2LR) included in the 9-valent vaccine and 13 others not included on it. This process uses SPF10 primers to amplify a 65 bp fragment of the L1 open reading frame of HPV, followed by a reverse-hybridizationfor specific HPV genotypes by comparing the results to standardized kit controls. Cervical cytology was acquired for all participants. Data was collected from 186 women negative to intraepithelial lesions (NILM), 65 with low-grade lesions (LGSIL), 23 atypical squamous cells of undetermined significance (ASCUS) and 94 with high-grade lesions (HGSIL).Among study results, the prevalence of any HR-HPV infection was high overall (~71.5%) and higher in women who had either LGSIL or HGSIL. The top leading HR types detected were 51 (20.4%), 16 (18.5%), 52 (13.60%), 33 (13.00%) and 56 (11.00%, with other types including HPVs 35,39, 68 or 59.Nearly 34.00% of the identified cervical HR-HPV types, are not included in the 9-valent vaccine. The most common HPV types in HGSIL, included HR HPV types 16 (30.9%), 52 (18.10%), 51 (14.9%) and 33 (10.60%). In this group, only 35.20% were HPV16/18. The other 64.80% were other HR-HPV types and, based on the ASCCP guidelines, would not require a colposcopy, and could be observed in one year. Among these HGSIL (n=94) 48.9% of the HPV types were not included in the vaccine. HPV 51 was the most dominant in ASCUS (26.10%), LGSIL (20%), and women who were negative for intraepithelial lesions (NILM 22.6%). Additionally, the most prevalent HPV-HR serotypes across all cytology categories in the vaccinated cohort were 52 (11.14%), 16 (8.02%) and 31 (7.56%), whereas in the non-vaccinated cohort were HPV 16 (20.6%), 51 (17.55%), 33 (13.33%), 52 (12.29%), and 56 (11.94%).In conclusion, the high burden of other high-risk types not covered by the vaccine in women with high-grade lesions suggests that delaying immediate colposcopy might limit the identification of cervical lesions. Even though this is not a population-based study, the high prevalence of these other HR-HPV types calls for their inclusion in future generations of the vaccine. Study sponsored by 2U54MD007600-36 (8538) Research Centers in Minority Institutions of the University of Puerto Rico (NIH/NIMHD). Citation Format: Romaguera Josefina, Bianka Morales, Andrea Cortes, Ana Rosario, Andrea Padilla-Bou, Maria Frontera, Claudia Rosado, Daniela Cargas-Robles, Ana P. Ortiz, Filipa Godoy-Vitorino. Prevalence of cervical high risk HPV serotypes not covered by the 9vt vaccine in a clinic-based sample of Hispanic women living in Puerto Rico [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 2141.

Mitoxantrone 2HCl’s adroit activity against cervical cancer replication and maintenance proteins: a multitargeted approach

Cervical cancer poses a significant global health challenge, ranking as the fourth most common cancer among women worldwide and resulting in approximately 300,000 deaths yearly, predominantly caused by high-risk human papillomavirus strains (HPV), mainly types 16 and 18. The scenario poses the urgent need of the hour to develop effective treatment strategies that can address the complexity of cervical cancer and multitargeted inhibitor designing that holds promise as it can simultaneously target multiple proteins and pathways involved in its progression and have the potential to enhance treatment efficacy, reduce the likelihood of drug resistance. In this study, we have performed multitargeted molecular docking of FDA-approved drugs against cervical cancer replication and maintenance proteins- Xenopus kinesin-like protein-2 (3KND), cell division cycle protein-20 (4N14), MCM2-histone complex (4UUZ) and MCM6 Minichromosome maintenance (2KLQ) with HTVS, SP and XP algorithms and have obtained the docking and MM\\GBSA score ranging from −8.492 to −5.189 Kcal/mol and −58.16 to −39.07 Kcal/mol. Further, the molecular interaction fingerprints identified ALA, THR, SER, ASN, LEU, and ILE were among the most interacted residues, leaning towards hydrophobic and polar amino acids. The pharmacokinetics and DFT of the compound have shown promising results. The complexes were simulated for 100 ns to study the stability by computing the deviation, fluctuations, and intermolecular interactions formed during the simulation. This study produced promising results, satisfying the criteria that Mitoxantrone 2HCl can be a multitargeted inhibitor against cervical cancer proteins—however, experimental validation is a must before human use. Communicated by Ramaswamy H. Sarma

Screening for High-Risk Human Papillomavirus Reveals HPV52 and HPV58 among Pediatric and Adult Patient Saliva Samples.

Previous research has demonstrated that the human papillomavirus (HPV) can infect a wide range of human tissues, including those within the oral cavity. High-risk oral HPV strains have been associated with the development and progression of oral cancers, including oral squamous cell carcinomas. Although many studies have examined the prevalence of the high-risk strains HPV16 and HPV18, far fewer have assessed the prevalence of other high-risk HPV strains. An approved study protocol was used to identify HPV52 and HPV58 among clinical samples (n = 87) from a saliva biorepository. Quantitative polymerase chain reaction (qPCR) and validated primers for HPV52 and HPV58 were used to facilitate this screening. This screening demonstrated that a total of n = 4/45 or 8.9% of adult saliva samples harbored high-risk HPV52, and n = 2/45 or 4.4% tested positive for high-risk HPV58. In addition, a total of n = 6/42 or 14.3% of the pediatric saliva samples tested positive for high-risk HPV, including n = 5/42 or 11.9% with HPV52 and n = 3/42 or 7.1% for HPV58. These data demonstrate the presence of the high-risk oncogenic HPV52 and HPV58 strains among both adult and pediatric clinical patient samples. More detailed longitudinal research must be conducted to determine whether this prevalence may be increasing or decreasing over time. In addition, these data strongly support public health prevention efforts, such as knowledge and awareness of the nine-valent HPV vaccine covering additional high-risk strains, including HPV52 and HPV58.

Applying the COM-B behaviour model to understand factors which impact 15-16 year old students' ability to protect themselves against acquirement of Human Papilloma virus (HPV) in Northern Ireland, UK.

High-risk strains of Human Papillomavirus (HPV) can lead to the development of a number of cancers including cervical, vulvar, penile, anal and oropharyngeal. HPV vaccination programmes offer the HPV vaccine to males and females 12-13 years old in schools throughout the UK. However, knowledge of HPV remains low in post-primary schools. The aim of this study is to capture 15-16 year old students' perceptions regarding the current provision of HPV education, and whether providing HPV education to 15-16 year olds could influence their intention to be vaccinated and/or future sexual health decisions related to HPV. Between 5th November 2021 and 6th May 2022, seven focus groups were conducted with 34 students in post-primary schools in Northern Ireland, United Kingdom. The data was analysed using the COM-B behaviour model to explore the perceived facilitators and barriers impacting students' ability to protect themselves from acquirement of HPV. Students perceived their knowledge of HPV to be poor and supported the addition of comprehensive mandatory HPV education at 15-16 years old when many of them were becoming sexually active. They identified barriers including lack of parental education, school ethos and religion and insufficient education regarding their legal rights to self-consent to HPV vaccination. Students felt that removal of these barriers would lead to safer sexual practices, increased awareness of the importance of HPV screening and increased HPV vaccination uptake. The recommendations provided by students need to be supported by the Education Authority in conjunction with the Department of Health in order to be successfully implemented into the post-primary school curriculum.

Rapid immunoassay for dual-mode detection of HPV16 and HPV18 DNA based on Au@PdPt nanoparticles.

Cervical cancer (CC) remains one of the most severe global health challenges affecting women, primarily due to persistent infection with high-risk human papillomavirus (HPV) subtypes, particularly with HPV16 and HPV 18. Effective detection of these high-risk HPV strains is crucial for CC prevention. Current screening programs for HPV DNA include PCR and in situ hybridization, which are accurate and sensitive. However, these approaches demand a high level of expertise, along with expensive instruments and consumables, thus hindering their widespread use. Therefore, there is a compelling demand to develop an efficient, straightforward, and cost-effective method. Herein, we propose a lateral flow immunoassay (LFIA) method based on Au@PdPt nanoparticles for the simultaneous detection and genotyping of HPV16 and HPV18 within 15 min. This innovative approach allows for qualitative assessment by the naked eye and enables semi-quantitative detection through a smartphone. In this study, under optimal conditions, the qualitative visual limits of detection (vLOD) for HPV16 and HPV18 reached 0.007 nM and 0.01 nM, respectively, which were 32-fold and 20-fold more sensitive than conventional AuNPs-LFIA for HPV16 and HPV18, respectively. Meanwhile, semi-quantitative limits of detection (qLOD) for HPV16 and HPV18 were 0.05 nM and 0.02 nM, respectively. In conclusion, our formulated approach represents a significant step forward in HPV detection and genotyping, with the potential to enhance accessibility and effectiveness in the early diagnosis of CC at the point of care and beyond.

Head and neck cancers: epidemiology, diagnosis and treatments

Introduction: Head and neck cancers (HNC) affect many subsites in the upper aero-digestive tract. The risk factors include tobacco smoking, chewing betel nut/paan, excessive alcohol consumption, hereditary factors and viruses such as human papillomavirus (HPV) and Epstein–Barr virus (EBV). Early diagnosis, lifestyle changes and HPV vaccination will improve survival. Epidemiology: Globally, recent estimates from GLOBOCAN shows there are 890,000 cases of head and neck cancers annually and 450,000 deaths annually (1). There is an increasing incidence of oral cavity, lip, buccal cancers in the developing world due to higher consumption of tobacco, alcohol and chewing areca nut. There has been an increasing incidence of some HNC due to high-risk strains of human papillomavirus (HPV) (2). Cancers caused by HPV include tonsil cancer, tongue base cancer and unknown primary cancers. The EBV causes nasopharyngeal cancers especially in the Far East. There is a decreasing incidence of some cancers caused by smoking such as laryngeal and hypopharyngeal cancers mainly due to the reduction in smoking rates in some developed countries. Overall, there is a predicted increase in HNC of up to 30% annually by 2030 (2). The HPV-associated cancers affect mainly younger males, who do not necessarily smoke or drink alcohol. The HPV is a strong prognostic factor so patients with HPV positive cancers respond better to treatment as there are less genetic mutations when compared to cancers driven by tobacco smoking. These trends are alarming with socioeconomic impacts. Diagnosis: Symptoms of HNC include difficulty swallowing, persistent sore throat, difficulty breathing, hoarseness, neck lumps, referred pain to the ear, weight loss, and systemic symptoms in advanced disease. A full ENT examination is performed of the oral cavity, oropharynx, neck and ideally flexible nasendoscopy. Ultrasound-guided FNAC or core biopsy of neck lumps are performed. Cross-sectional imaging with CT or MRI scans followed by tumour biopsies either under local or general anaesthetic. Tumour biopsies are assessed using H&amp;E stains, and tests for HPV detection (p. 16 immunohistochemistry, in situ hybridisation or polymerase chain reaction). A PETCT scan is useful for staging cancers, identifying the origin of unknown primary cancers and for surveillance. Treatments: The head and neck cancer multidisciplinary team reviews all investigations and recommends either curative or palliative treatment options that are in every patient’s best interests. Surgery can be open, endoscopic or with the use of a robot. Microvascular reconstruction with flaps is performed as necessary to improve function and quality of life. Oncologic treatments include intensity-modulated radiotherapy (IMRT), which can be combined with chemotherapy. Immunotherapy is a second-line treatment for recurrent HNC currently. Advanced cancers can be treated with palliative intent or best supportive care especially if the patients are frail and have significant comorbidities. There are ongoing clinical trials and research studies exploring better, less-toxic treatments. Multiomics approach and artificial intelligence are exciting developments. Conclusion: There is an increasing incidence of some HNC especially cancers driven by tobacco smoking, alcohol consumption and high-risk human papillomaviruses. Smoking cessation, HPV vaccination, early diagnosis and improvements in treatments are important factors in ensuring good outcomes.

HPV Vaccine Usage Among the U.S. Military Academy Corps ofCadets (2018-2025).

Human papillomavirus (HPV) is a common sexually transmitted virus that infects over 13 million people every year. Over 80% of sexually active adults will acquire HPV at some point in their lives, which is concerning since certain high-risk strains of HPV can cause six types of cancer. Vaccination against HPV is safe and effective, but despite high vaccine efficacy, vaccination rates are low among both service members and civilians. We conducted a retrospective, cross-sectional study to identify the percentage of United States Military Academy (USMA) Cadets who had received at least one HPV vaccine and those who completed the vaccine series. Deidentified vaccination and demographic data were retrieved from the Defense Health Agency Military Health System Data Repository (MDR) for all Cadets who were enrolled at USMA between January 2018 and May 2022 (graduating classes of 2018-2025). To identify the population of Cadets for our study and confirm presence of "any" vaccine in the MDR, Tdap vaccination information was also retrieved. The study population was defined as any Cadet who was enrolled at USMA between January 2018 and May 2022 (graduating classes of 2018-2025) and had record of an HPV and/or Tdap vaccine in the MDR. We compared demographic information between the identified population and known demographics of the USMA population to confirm that the retrieved data were consistent with population demographics. Descriptive statistics were performed to identify demographic differences based on vaccinated and unvaccinated Cadets and to determine the percentage of Cadets who received at least one HPV vaccine. Vaccine series completion was defined as the receipt of three HPV vaccine doses among those who reported receiving at least one dose of HPV vaccine or two doses if vaccinated before the age 15. A total of 9,567 Cadets were assessed for eligibility with 9,433 having Tdap and/or HPV vaccine on record. Of these Cadets, 5,738/9,433 (60.8%) had received at least one HPV vaccine. Of those starting the series, 4,492 completed the two- or three-dose series for a completion rate of 47.6%. We found HPV vaccine completion rate among female Cadets (55.6%) is higher than that of male Cadets (45.2%). More Cadets from minority groups received one vaccine; however, full completion rates were similar for both the groups (48.1%). In contrast, the percentage of Cadets vaccinated against Tdap was 97.2%. Most of those vaccinated received their first vaccine between the ages of 11 and 15 (53.0%) and their final vaccine after they turned 16 (68.9%). Though the vaccination rate among the Corps of Cadets is comparable to the public, it is still less than the 80.0% goal set by the Healthy People 2030 objective. Based on these results, we recommend that the USMA modify its policy on HPV vaccine administration to encourage more vaccine uptake. We also conclude that further studies on the rationale for avoiding the vaccine are necessary to better inform educational campaigns and mitigate stigma.

Screening for High-Risk Oral Human Papillomavirus (HPV31, HPV33, HPV35) in a Multi-Racial Pediatric and Adult Clinic Patient Population.

Many human papillomavirus (HPV) strains induce cancer in the cervix and the oral cavity. Although high-risk strains including HPV16 and HPV18 are commonly known, additional high-risk strains including HPV31, HPV33, and HPV35 may also induce carcinogenesis, and much less is known about their prevalence. Using an approved protocol, samples from a salivary biorepository were screened to find pediatric and adult samples from a multi-ethnic, university-based patient clinic population. A total of N = 86 samples from the saliva biorepository met the quality and concentration standards and were screened for high-risk HPV. qPCR screening of adult samples revealed n = 10/45 or 22% were HPV31- or HPV33-positive. In addition, a total of n = 9/41 or 21.9% of pediatric samples were either HPV31- or HPV33-positive (or both). No samples harbored HPV35. Most samples were derived from patients within the recommended vaccination or catch-up age range (age 9-45 years). These results demonstrated that a significant percentage of patients harbor additional high-risk HPV strains within the oral cavity, including HPV31 and HPV33. These data support oral healthcare provider recommendations for the newer nine-valent vaccine, which includes both HPV31 and HPV33.

Comparative Study of Intralesional Measles–Mumps–Rubella Vaccine versus Needling-Induced Autoinoculation in the Management of Genital Warts

Abstract Background Genital warts caused by human papillomavirus (HPV) are one of the most common sexually transmitted infections, especially among women. Genital HPV infection has a relatively long incubation period up to 8 months. It is known to have a high recurrence rate, and the infection by certain high-risk HPV strains is known to be associated with malignancies of cervix, penis, vulva, vagina, and anus. Thus, factors such as long latency, lesions’ multiplicity, high recurrence rate, and the tendency to malignant transformation, are essential challenges during management of genital HPV infections. The clinical outcome of traditional treatment modalities; such as podophyllotoxin, imiquimod, cryotherapy, electrocautery, trichloroacetic acid, photodynamic therapy, and laser, is limited to individual lesions. Therefore, they are usually inconvenient for patients with multiple and/or recurrent lesions. Aim of the Work to evaluate the safety and efficacy of intralesional injection of MMR vaccine in comparison with needling-induced autoinoculation in the treatment of genital warts. Patients and Methods Our study included 50 patients with multiple and recurrent genital warts (more than 4 genital warts) divided into two equal matched groups. One group was subjected to MMR injection and the other subjected to needling-induced autoinoculation every two weeks for maximum three sessions. Follow-up was done for 8 weeks after last session. Results This study reports that both treatment options showed statistically significant value in treatment of genital warts, and here was no statistically significant difference between both study groups as regard response to treatment. Conclusion both MMR and needling are simple and effective modalities of immunotherapy for treatment of multiple genital warts with excellent safety profile. The only disadvantage is the long time taken for immune response to occur. Combination treatment plan can overcome this disadvantage. Needling-induced autoinoculation; being more safe and inexpensive, may be considered as a competing immunotherapeutic treatment modality for multiple and recurrent genital warts.

Development of a simplified and cost-effective sample preparation method for genotyping of human papillomavirus by next-generation sequencing.

High-risk human papillomavirus (HPV) infection is the most common cause of cervical cancer, but low-risk HPV strains can sometimes also be involved. Although HPV genotyping techniques used in clinical diagnosis cannot detect low-risk HPV, next-generation sequencing (NGS) can detect both types. However, DNA library preparation is complicated and expensive. The aim of this study was to develop a simplified, cost-effective sample preparation procedure for HPV genotyping based on next-generation sequencing (NGS). After DNA extraction, a first round of PCR was performed using modified MY09/11 primers specific for the L1 region of the HPV genome, followed by a second round of PCR to add the indexes and adaptors. Then, the DNA libraries were purified and quantified, and high-throughput sequencing was performed using an Illumina MiSeq platform. The sequencing reads were compared with reference sequences for HPV genotyping. The limit of detection for HPV amplification was 100 copies/µl. Analysis of the correlation of pathological cytology with the HPV genotype in individual clinical samples showed that HPV66 was the most common genotype found in the normal stage, whereas HPV16 was the main genotype found in low-grade squamous intraepithelial lesions, high-grade squamous intraepithelial lesions, and cervical cancer. This NGS method can detect and identify several HPV genotypes with 92% accuracy and 100% reproducibility, and it shows potential as a simplified and cost-effective technique for large-scale HPV genotyping in clinical samples.

The crossroads: divergent roles of virus-specific CD4+ T lymphocytes in determining the outcome for human papillomavirus infection.

Despite the widespread availability of effective prophylactic vaccines to prevent human papillomavirus (HPV) infection, HPV remains a major health burden. For health care systems in countries with the capacity for vaccine roll out, incomplete strategies result in citizens with naturally occurring infection, who are at an a posteriori risk of HPV-driven disease. Genital HPV infection is the most common sexually transmitted virus globally. Those classified as high-risk HPV strains are more likely to generate persistent disease. Within this group, HPV16 and 18 are the most prevalent and likely to induce persistent high-grade squamous intraepithelial neoplasia; neoplasia is a large step toward cancerous growth known as a squamous cell carcinoma which contribute to all cervical, 70% of oropharyngeal, 78% of vaginal and 88% of anal cancers. This review will illuminate the relevance of CD4+ T lymphocytes in determining the outcome of papillomavirus infection from the perspective of oropharyngeal and anogenital HPV-driven disease in the immune competent and immunocompromised. The focus is on recent investigations for this "silent" pandemic among current global health crises that should not be forgotten. Informing effective strategies that control viral infection through naturally acquired or induced immunity will identify aspects of scientific and clinical practice that may improve outcome.

Molecular Screening for High-Risk Human Papillomaviruses in Patients with Periodontitis.

Members of the Papillomaviridae family account for 27.9-30% of all infectious agents associated with human cancer. The aim of our study was to investigate the presence of high-risk HPV (human papilloma virus) genotypes in patients with periodontitis and a pronounced clinical picture. To achieve this goal, after proving the bacterial etiology of periodontitis, the samples positive for bacteria were examined for the presence of HPV. The genotype of HPV is also determined in samples with the presence of the virus proven by PCR (polymerase chain reaction). All positive tests for bacteria associated with the development of periodontitis indicated the presence of HPV. There was a statistically significant difference in HPV positive results between the periodontitis positive target group and the control group. The higher presence of high-risk HPV genotypes in the target group, which was also positive for the presence of periodontitis-causing bacteria, has been proven. A statistically significant relationship was established between the presence of periodontitis-causing bacteria and high-risk strains of HPV. The most common HPV genotype that tests positive for bacteria associated with the development of periodontitis is HPV58.