Human Papillomavirus Research Articles

Comprehensive Analysis of Codon Usage Bias in Human Papillomavirus Type 51.

Human papillomavirus type 51 (HPV-51) is associated with various cancers, including cervical cancer. Examining the codon usage bias of the organism can offer valuable insights into its evolutionary patterns and its relationship with the host. This study comprehensively analyzed codon usage bias in HPV-51 by examining 64 complete genome sequences sourced from the NCBI GenBank database. Our analysis revealed no noteworthy preference for codon usage in HPV-51 overall. However, there was a noticeable bias towards A/T-ending codons, accompanied by GC3s below 32%. Dinucleotide frequency analysis revealed reduced frequencies for ApA, CpG, and TpC dinucleotides, while CpA and TpG dinucleotides were more frequent than others. Relative Synonymous Codon Usage analysis revealed 30 favored codons, primarily concluding with A/T nucleotides. Further analysis using Parity Rule 2, Effective Number of Codons plot, and neutrality plot indicated a balance between mutational pressure and natural selection, with natural selection being the primary force shaping codon usage bias. The Isoacceptor tRNA Pool analysis indicates that HPV-51 has a higher translation efficiency within the human cellular translational system. Moreover, the Codon Adaptation Index and Relative Codon Deoptimization Index analyses suggested a moderate adaptation of HPV-51 to human codon preferences. Our discoveries offer valuable perspectives on how HPV-51 evolves and uses genetic codes, contributing to a deeper comprehension of its endurance and disease-causing potential.

Effectiveness of Digital Education on Human Papillomavirus Knowledge, Vaccination Intent and Completion Rates in Adolescents and Young Adults: A Meta-Analysis.

To examine the effects of digital educational intervention on HPV knowledge, vaccination intent and completion rates among adolescents and young adults. A systematic review and meta-analysis. The study followed PRISMA guidelines. Studies included randomised controlled trials assessing digital HPV educational interventions on individuals aged 9-26 years. Odds ratios (ORs), confidence intervals (CIs) and standardised mean differences (SMDs) were calculated and analysed with fixed- and random-effects models, depending on the degree of heterogeneity. Seven databases (Medline, PubMed, CINAHL, Cochrane Library, Web of Science, EMBASE and ASC) were searched from inception through April 9, 2024. Twelve studies enrolled 4925 participants were included. Six studies demonstrated that the intervention group significantly had higher HPV knowledge compared to the control group. Five studies reported a significant improvement on vaccination intent and vaccine completion rate. Subgroup analysis of the completion rates indicated that male participants demonstrated significantly greater vaccine competed rates. A tailored educational intervention was likely to effectively enhance HPV vaccine completion rates. Our findings confirmed that digital education was beneficial in enhancing adolescents and young adults' HPV knowledge, vaccination intention and vaccine completion rates. The tailored education might be considered prioritised in the design of interventions, while also considering the impact of gender on digital education. Digital interventions for HPV vaccinations require at least 7 months of follow-up, highlighting the vital role of tailored education for high-risk groups in designing effective interventions. The efficacy of digital interventions for HPV vaccination may differ across genders. There was no direct patient or public contribution, as this is a review of previous research. CRD-42023406919.

Health mediation for promoting cancer screening and vaccination in deprived neighbourhoods in France

Abstract Social inequalities in health affect access to healthcare and prevention. In Marseille, these inequalities are pronounced, with 26% of the population below the poverty line. In September 2022, a health mediation and outreach program was launched in deprived neighbourhoods to promote cancer screening and vaccination by going towards populations and providing information and orientation adapted to individuals’ health literacy and autonomy. We aimed to evaluate the effectiveness of this intervention. A repeated cross-sectional study compared knowledge, attitudes and practices about cancer screening and vaccination before and after health mediation interventions and between control and intervention neighbourhoods. Trained investigators administered a questionnaire door-to-door to individuals aged 18-74 years in randomly selected households. A first T0 survey was conducted in September 2022, and a second T1 survey is underway in May 2024, in 13 intervention and 26 control neighbourhoods. We compared the before-and-after participation rates and associated risk factors for cancer screening and vaccination between both areas using mixed regression models. Of the 2,647 respondents at T0, 61% were women, 43% non-native French speakers, 40% unemployed, and 53% had public health insurance. Survey respondents were socially deprived and had lower participation rates in cancer screening and vaccination compared to national levels. At T0, the cancer screening participation rate was 31% for colorectal cancer, 51% for breast cancer, and 68% for cervical cancer. Factors associated with non-participation were not believing in the effectiveness of cancer screening, not being aware of its existence or not speaking French. At T0, only 54% knew about human papillomavirus vaccine and only 35% of eligible women were vaccinated. A comparison of these T0 results with results of the ongoing T1 survey will be presented, in order to assess the effectiveness of this health mediation intervention. Key messages • Health mediation promotes cancer screening and vaccination by going towards populations in deprived neighbourhoods and providing information adapted to individuals’ health literacy and autonomy. • Survey respondents were socially deprived and had lower participation rates in cancer screening and vaccination compared to national levels.

Vaginal self-sampling for HPV in the context of cervical cancer screening

Abstract Background Effective cervical cancer screening programme has the potential to improve disease outcomes, yet women’s participation rates in Latvia remain suboptimal. Utilizing vaginal self-sampling for HPV, a convenient method, has demonstrated efficacy in boosting participation in under-screened populations. We analysed sociodemographic factors, as well as health behaviours with the preference for vaginal self-sampling procedures for early detection of cervical cancer. Methods Cross-sectional survey (2021-2022) included 1313 women in Latvia. Sampling was done in the colposcopy clinic and among GP practices. In the univariate analysis cervical cancer examination preference (self-test or by a physician) was analysed in association sociodemographic factors, participation in the screening, HPV status, study group, and health-related behaviour. Financed by “Internal consolidation of RSU and external consolidation of RSU with LSPA” (No. 5.2.1.1.i.0/2/24/I/CFLA/005), The EU Recovery and Resilience plan and the state budget, Grant Nr. RSU-PAG-2024/1-0016. Results 48.6 % (n = 538) of the women would prefer to use a vaginal self-test. Higher odds of the vaginal self-test preference were observed among Latvian (OR = 1.4 (1.1-1.8) vs other nationality women, but no other sociodemographic factors showed statistically significant associations. Women in the colposcopy study group (vs GP practices) were more likely to utilize self-sampling (OR = 1.8 (1.4-2.5). Non-participation in cervical cancer screening was related to 2.4 (1.6-3.6) higher odds of self-test preference, but knowledge about screening was related to 1.5 (1.1-2.0) times higher odds. Women who were HPV-negative were more likely to prefer vaginal self-test for HPV (OR = 1.4 (1.1-1.8) in comparison to HPV-positive women. Health-related behaviour did not show any associations. Conclusions Vaginal self-test for HPV can be effectively used to reach under-screened populations and enhance cervical cancer screening coverage. Key messages • The implementation of vaginal self-sampling for HPV testing has the potential to improve participation rates in cervical cancer screening programs among under-screened populations. • Outreach and education activities tailored to specific target groups in population could enhance level of the cervical cancer screening uptake.

High prevalence of cardiotropic viruses in endomyocardial biopsies from patients with inflammatory cardiomyopathy demonstrated by a novel targeted NGS approach

Abstract Background Viral infection of the heart muscle is a common cause of myocarditis and viral persistence can lead to chronic inflammatory cardiomyopathies (DCMi). A number of viruses including parvovirus B19 (B19V), adenovirus (AdV), cytomegalovirus (CMV), Epstein-Barr virus (EBV), herpes virus 6 (HHV-6) and enteroviruses (EV) are known to infect the myocardium, but their prevalence and role in persisting DCMi are not well understood. Virological etiologies can only be determined via endomyocardial biopsy (EMB), but the low tissue amount limits the number of conventional viral nucleic acid tests (virus-specific PCR) that can be performed in parallel. This study aimed to detect known and novel cardiotropic viruses in EMB of DCMi patients using a targeted next generation sequencing (NGS) approach. Methods A cohort of 33 patients with inflammatory cardiomyopathy (DCMi) (LVEF=29±12%) were retrospectively analyzed and compared to previous results of virus-specific PCR. DNA and RNA extracted from EMB were used for sequencing library preparation, and viral nucleic acids were enriched via a custom myBaits hybridization capture approach. Enriched libraries were sequenced on an Illumina MiSeq-platform in paired-end mode (500.000 reads/sample), and reads were taxonomically classified via Kraken2 and mapped against viral reference genomes using BWA-MEM2 or HiSat2, and subsequently deduplicated. Viral reads detected via both Kraken2 and mapping were classified as valid. Results Targeted NGS confirmed 19 out of 22 (86%) of the previous PCR-based viral detections. However, NGS was able to detect B19V DNA and RNA in an additional 11 and 15 patient samples respectively; CMV DNA/RNA in additional 5 and 4 samples respectively; EBV DNA/RNA in additional 5 and 1 samples respectively; and HHV-6 DNA/RNA in additional 3 and 1 samples respectively. Furthermore, viral reads of adenovirus type 2, adenovirus-associated virus type 2 (AAV-2), herpes viruses 7 and 8, and human parvovirus 4 were also found among the cohort. Thus, targeted NGS was able to identify 82 viral infections in a cohort of 33 DCMi patients, while only 22 were found using routine PCR tests. For routinely tested B19V, the use of the new NGS diagnostic approach improved sensitivity by 42% and specificity by 72%. Conclusions The presented NGS method represents a powerful new tool for the diagnosis of viral and inflammatory heart disease. The sensitivity is significantly higher than with conventional PCR approaches and the taxonomic classification is more specific. This enables the detection of previously false-negative routine viruses as well as potentially new cardiotropic pathogens from limited bioptic patient material – thus significantly increasing the diagnostic yield of EMB. In addition, our study demonstrates a high prevalence of non-enteroviral cardiotropic viruses in DCMi patients, shedding new light on the etiology of this heterogenous diseases and paving the way for more specific future treatments.

Synergistic pairing of synthetic image generation with disease classification modeling permits rapid digital classification tool development

Machine-learning disease classification models have the potential to support diagnosis of various diseases. Pairing classification models with synthetic image generation may overcome barriers to developing classification models and permit their use in numerous contexts. Using 10 images of penises with human papilloma virus (HPV)-related disease, we trained a denoising diffusion probabilistic model. Combined with text-to-image generation, we produced 630 synthetic images, of which 500 were deemed plausible by expert clinicians. We used those images to train a Vision Transformer model. We assessed the model’s performance on clinical images of HPV-related disease (n = 70), diseases other than HPV (n = 70), and non-diseased images (n = 70), calculating recall, precision, F1-score, and Area Under the Receiver Operating Characteristics Curve (AUC). The model correctly classified 64 of 70 images of HPV-related disease, with a recall of 91.4% (95% CI 82.3%-96.8%). The precision of the model for HPV-related disease was 95.5% (95% CI 87.5%-99.1%), and the F1-score was 93.4%. The AUC for HPV-related disease was 0.99 (95% CI 0.98-1.0). Overall, the HPV-related disease classification model demonstrated excellent performance on clinical images, which was trained exclusively using synthetic images.

Application of mass cytometry in multiparametric characterization of precancerous cervical lesions.

Cervical cancer (CC) is the fourth most common malignant tumor in women worldwide. Detecting different biomarkers together on single cells by novel method mass cytometry could contribute to more precise screening. Liquid-based cytology (LBC) cervical samples were collected (N = 53) from women categorized as normal and precancerous lesions. Human papillomavirus was genotyped by polymerase chain reaction, while simultaneous examination of the expression of 29 proteins was done by mass cytometry (CyTOF). Differences in cluster abundances were assessed with Spearman's rank correlation as well as high dimensional data analysis (t-SNE, FlowSOM). Cytokeratin (ITGA6, Ck5, Ck10/13, Ck14, Ck7) expression patterns allowed determining the presence of different cells in the cervical epithelium. FlowSOM analysis enabled to phenotype cervical cells in five different metaclusters and find new markers that could be important in CC screening. The markers Ck18, Ck18, and CD63 (Metacluster 3) showed significantly increasing associated with severity of the precancerous lesions (Spearman rank correlation rho 0.304, p = 0.0271), while CD71, KLF4, LRIG1, E-cadherin, Nanog and p53 (Metacluster 1) decreased with severity of the precancerous lesions (Spearman rank correlation rho -0.401, p = 0.0029). Other metaclusters did not show significant correlation, but metacluster 2 (Ck17, MCM, MMP7, CD29, E-cadherin, Nanog, p53) showed higher abundance in low- and high-grade intraepithelial lesion cases. CyTOF appears feasible and should be considered when examining novel biomarkers on cervical LBC samples. This study enabled us to characterize different cells in the cervical epithelium and find markers and populations that could distinguish precancerous lesions.

Electrochemical Immunosensor for the Sensitive Determination of Human Papillomavirus (HPV) 16 L1 Capsid Protein: A Leap in Cervical Cancer Diagnosis

Human Papillomavirus (HPV) is the principal cause of cervical cancer, which is still a prime universal health concern, especially in underdeveloped nations where access to advanced screening techniques is often restricted. Herein, we propose an electrochemical immunosensor for the determination of HPV 16 L1 protein, a key biomarker associated with cervical carcinogenesis. The developed immunosensor, employing glassy carbon electrode (GCE) enhanced with gold nanoparticles, provides a highly sensitive, specific, and cost-effective approach for early screening of cervical cancer. An optimized stepwise fabrication process which includes electrode surface modification and antibody immobilization, was used to enhance sensor performance. Characterization studies confirmed the effective modification of electrodes and the selectivity of immunoreactions. With an impressive limit of detection (LOD) of 0.033 fg mL−1, the immunosensor showed a linear response to L1 protein concentrations ranging from 0.1 fg mL−1 to 1 ng mL−1. Additionally, the immunosensor exhibits excellent specificity, stability, reproducibility, and regeneration capabilities. The performance of the immunosensor was compared with the enzyme-linked immunosorbent assay (ELISA) by analyzing clinical samples (positive: n = 12; healthy: n = 5) showed satisfactory results. The findings indicated that the proposed sensing platform has the potential to be utilized for the early diagnosis of cervical cancer.

The Burden and Prevention of Human Papillomavirus (HPV) Infections and Cervical Cancer in India: A Literature Review

The Burden and Prevention of Human Papillomavirus (HPV) Infections and Cervical Cancer in India: A Literature Review

A case of squamous cell carcinoma of the lung misdiagnosed as tuberculosis. Is HPV infected by oral sex the causative agent?

BackgroundThe integration of high-risk human papilloma virus (HPV) DNA into the human genome has been implicated in cervical carcinogenesis and head and neck squamous cell cancer. However, its role in lung squamous cell carcinoma is not well understood. In addition, tuberculosis (TB) and lung cancer(LC) share similar clinical symptoms and imaging features, increasing the risk of misdiagnosis.Case PresentationThe patient presented with a 16-month history of hemoptysis, chest pain, and occasional fatigue, without fever, chills, or history of mechanical damage or autoimmune diseases. Examination revealed normal vital signs and laboratory parameters, except for a positive interferon-gamma release assay indicating tuberculosis infection. Bronchoscopic examinations identified congestion and edema of the tracheal wall, along with a tiny lesion in the right wall of the trachea. She had been misdiagnosed with tuberculosis. However, the diagnosis of squamous cell carcinoma was eventually confirmed by endoscopic biopsy. The patient’s macrogenomic second-generation sequencing (mNGS) of the bronchoscopic biopsy specimen was positive for HPV-16.The patient’s sex partner tested positive for HPV-16 in penile scrapings, indicating HPV transmission through oral sex.ConclusionsThis case highlights the potential for HPV infection acquired through oral sex to lead to lung squamous cell carcinoma. It emphasizes the importance of considering HPV-associated malignancies in patients with respiratory symptoms who engage in oral sexual behaviors.

A scoping review of human papillomavirus and cervical cancer knowledge, attitudes, practices, and prevention among female sex workers in Africa

Background Global initiatives have emphasized the elimination of cervical cancer (CC) among female sex workers (FSW) in Africa. Yet screening remains low, and few interventions have been outlined to target this group. This scoping review sought to understand the knowledge, attitudes, and practices (KAP) among FSW in Africa regarding human papillomavirus (HPV) and CC prevention, and to identify the most effective intervention strategies. Methods A systematic literature search was performed in PubMed, Scopus, Web of Science, and African Index Medicus for work published between January 2012 through August 2022. Eligible studies included those relating to HPV and CC prevention among FSW in Africa. Studies were categorized as KAP, intervention, or both. A Logic Model was used to guide content analysis of the interventions, and a thematic analysis of all studies was performed. Results The search resulted in 79 articles of which 11 were included in the study. Six African countries were represented including South Africa, Mozambique, Uganda, Kenya, Ethiopia, and Nigeria. Five of the articles described KAP, while the other six described interventions. The intervention studies were categorized into 3 groups: “screen and treat”, self-collection HPV testing, and a “diagonal intervention” which included a multi-faceted approach. Conclusions Limited literature exists regarding KAP and interventions for HPV and CC prevention among FSW in Africa. While FSW in the literature had a moderate level of knowledge regarding HPV and CC prevention, studies identified a lack of detailed and nuanced knowledge. Successful uptake of screening was seen when services were provided at convenient locations, integrated into routine or HIV care, and recommended by healthcare providers. Future interventions should be context-specific, include improved counselling and education, and be integrated with other services.

Design and antiviral assessment of a panel of fusion proteins targeting human papillomavirus type 16.

Cervical cancer ranks as the third most prevalent malignancy in women worldwide. The persistence of Human papillomavirus (HPV) infection stands out as the foremost risk factor for cervical cancer development. Among the numerous HPV subtypes, HPV16 infection emerges as the primary pathogenic determinant of cervical cancer. To date, no specific drugs have been approved. In this study, we engineered two high-affinity fusion protein targeting HPV16 L1 protein based on the alpaca-derived single-domain antibody 2C12 previously obtained in our laboratory. These two fusion proteins exhibited potent neutralizing activity against HPV16 pseudovirus with IC50 values of 7.8 nM and 6.5 nM, respectively. Molecular docking analysis revealed that 2C12 formed ten pairs of hydrogen bonds with HPV16 L1, among which Arg39 and Thr100 established multiple pairs of hydrogen bonds with HPV16 L1, indicating their crucial roles in antigen-antibody binding process. These structural and biological findings underscore the effective binding capacity of these fusion proteins to HPV16, leading to reduced viral load and providing valuable insights into therapeutic antibody and vaccine development against HPV 16 infection.

Cervical cancer screening among women: A systematic literature review

Background: Cervical cancer is one of the major concerns of public health importance in today's world. It is a leading cause of mortality in women of reproductive age group worldwide, mainly in developing countries. It is almost always associated with human papilloma virus (HPV) infection. Reduction in mortality and morbidity due to cervical cancer is possible through early detection as a first step. Purpose: To investigate about cervical cancer screening among women. Method: A systematic literature review approach was employed to gather and assess data from PubMed, Science Direct, and Google Scholar. The keywords "cervical cancer screening," "adult women," "pap smear," "HPV vaccination," "behavior," and/or "health belief" were utilized for this purpose. A total of 79 items were identified. In all, the study comprised 7 papers that satisfied the specified criteria. Following that, we carry out a methodical examination and evaluation of the chosen papers in the current literature. Results: Variables associated with cervical cancer screening including Pap smear, the impact of HPV vaccination, behavioral patterns, and health-related views. Health beliefs frequently act as the main driving force for persons to voluntarily get cervical cancer screening. Preventive cervical cancer screening enables early detection, so potentially averting the development of the illness or limiting its progression. Conclusion: To advance the objective of eliminating cervical cancer as a global public health concern, it is necessary to enhance the accessibility and involvement in screening interventions.

Opportunities to advance cervical cancer prevention and care

Cervical cancer (CaCx) is a major public health issue, with over 600,000 women diagnosed annually. CaCx kills someone every 90 s, mostly in low- and middle-income countries. There are effective yet imperfect mechanisms to prevent CaCx. Since human papillomavirus (HPV) infections cause most CaCx, they can be prevented by vaccination. Screening methodologies can identify premalignant lesions and allow interventions before a CaCx develops. However, these tools are less feasible in resource-poor environments. Additionally, current screening modalities cannot triage lesions based on their relative risk of progression, which results in overtreatment. CaCx care relies heavily on genotoxic agents that cause severe side effects. This review discusses ways that recent technological advancements could be leveraged to improve CaCx care and prevention.

Spontaneous and post-interventional regression of cervical HPV infection.

Recent literature sources suggest that 15-20% of all malignant diseases have a viral aetiology. About 5% of these are caused by the human papillomavirus. The presence of papillomavirus is one of the strongest risk factors for development of a cervical pre-cancerous lesion and subsequent cervical cancer. The presented review provides a brief summary and characterisation of risk factors that influence spontaneous and post-interventional regression and persistence of papillomavirus in the cervical area.

Update on HPV-associated head and neck cancers-highlights of the 2024 ASCO Annual Meeting

Human papillomavirus (HPV)-associated head and neck squamous cell carcinoma (HNSCC) is becoming increasingly important in head and neck oncology. At this year's conference of the American Society of Clinical Oncology (ASCO), alarge number of papers were presented on the topic of HPV-associated HNSCC, particularly with regard to neoadjuvant treatment approaches, radiation de-escalation strategies, therapeutic vaccines, and treatment monitoring. In this context, study results on the treatment of HPV-related recurrent respiratory papillomatosis (RRP) were also presented. Based on contributions to the 2024 ASCO Annual Meeting, an insight into the latest developments in HPV-associated diseases of the head and neck is provided. The papers were reviewed for clinical relevance and contextualized based on current therapeutic concepts. Alarge number of studies on liquid biopsies (LB) were presented. It was shown that although the methods for analyzing LBs for HPV-positive patients are well developed and can be used for diagnostics, risk classification, treatment management, or tumor follow-up, the methods vary considerably, and their clinical application has not yet been sufficiently validated. With regard to therapeutic HPV vaccination, three large studies were presented for the treatment of recurrent/metastatic HPV-positive oropharyngeal squamous cell carcinoma (OPSCC). The only randomized study was on the vaccine ISA101b (peltopepimut-S) and did not reach its primary endpoint; however, the vaccine seemed to be highly effective in patients with a combined positive score (CPS) ≥ 20. Furthermore, data from aphaseIstudy on PRGN2012, an adenovirus-based immunotherapy used therapeutically for the treatment of recurrent respiratory papillomatosis (RRP), were presented. PRGN2012 led to areduction in surgical interventions for RRP, and the US Food and Drug Administration (FDA) designated PRGN2012 as abreakthrough therapy and orphan drug. However, the vaccine is not yet approved for the treatment of RRP.

Tumor Initiation and Progression in People Living on Antiretroviral Therapies

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

Cytologic features of gastric-type endocervical adenocarcinoma: Three cases report and literature review.

Cervical gastric-type adenocarcinoma shows gastric differentiation, and the tumor cell morphology appears benign and unrelated to human papillomavirus, which makes cervical gastric-type adenocarcinoma highly susceptible to misdiagnosis as normal glandular epithelium in cytologic diagnosis. We present 3 cases of gastric-type adenocarcinoma, with the first being a 57-year-old female with abnormal uterine bleeding and fluid drainage. The second patient was a 63-year-old female, and the third was a 59-year-old female with irregular vaginal bleeding after menopause. The 3 patients were diagnosed with cervical gastric-type adenocarcinoma by combining their history, clinical data, cytopathology, histopathology, and immunohistochemistry. Patient 1 underwent total hysterectomy and adnexectomy, but refused radiotherapy and chemotherapy. Patient 2 received a chemotherapeutic regimen, and patient 3 was treated with traditional Chinese medicine. Patient 1 was followed-up for 9 months and is currently in good general condition, while patients 2 and 3 were not followed-up. The "drunken honeycomb" cell arrangement is diagnostically important in liquid-based cytology, especially when three-dimensional spheroids are present, and may be a characteristic cytological finding of well-differentiated cervical gastric-type adenocarcinoma.

Dynamics and Optimal Control of a Stochastic Delayed Human Papillomavirus Epidemic Model with Media Coverage

Dynamics and Optimal Control of a Stochastic Delayed Human Papillomavirus Epidemic Model with Media Coverage

The full transcription map of cottontail rabbit papillomavirus in tumor tissues.

Cottontail rabbit papillomavirus (CRPV), the first papillomavirus associated with tumor development, has been used as a powerful model to study papillomavirus pathogenesis for more than 90 years. However, lack of a comprehensive analysis of the CRPV transcriptome has impeded the understanding of CRPV biology and molecular pathogenesis. Here, we report the construction of a complete CRPV transcription map from Hershey CRPV-induced skin tumor tissues. By using RNA-seq in combination with long-reads PacBio Iso-seq, 5' and 3' RACE, primer-walking RT-PCR, Northern blot, and RNA in situ hybridization, we demonstrated that the CRPV genome transcribes its early and late RNA transcripts unidirectionally from at least five distinct major promoters (P) and polyadenylates its transcripts at two major polyadenylation (pA) sites. The viral early transcripts are primarily transcribed from three "early" promoters, P90, P156, and P907 and polyadenylated at nt 4368 by using an early polyadenylation signal (PAS) at nt 4351. Like other low-risk human papillomaviruses and animal papillomaviruses, CRPV E6 and E7 transcripts are transcribed from three separate early promoters. Transcripts from two "late" promoters, P7525, and P1225, utilize either an early PAS for E1^E4 or a late PAS at 7399 for L2 and L1 RNA polyadenylation at nt 7415 to express capsid L2 and L1 proteins respectively. By using the mapped four 5' splice sites and three 3' splice sites, CRPV RNA transcripts undergo extensive alternative splicing to produce more than 33 viral RNA isoforms for production of at least 12 viral proteins, some of which without codon optimization are expressible in rabbit RK13 and human HEK293T cells. The constructed full CRPV transcription map in this study for the first time will enhance our understanding of the structures and expressions of CRPV genes and their contribution to molecular pathogenesis and tumorigenesis.