Human Papillomavirus Type Research Articles

CrRNA Conformation-Engineered CRISPR-Cas12a System for Robust and Ultrasensitive Nucleic Acid Detection.

Despite the widespread application of the CRISPR-Cas12a system in vitro diagnostics due to its high programmability and distinctive trans-cleavage activity, the susceptibility of its crRNA component to degradation and sensitivity to storage and working conditions poses a significant challenge to improving the practical efficacy of these diagnostic systems. Here, we show that engineered crRNA with a covalently closed circular structure (C-crRNA) can replace traditional linear crRNA to form functional complexes with Cas12a protein, significantly enhancing the anti-interference ability of the CRISPR-Cas12a system while maintaining its sensitivity and specificity. Based on this finding, a circular crRNA-mediated CRISPR molecular diagnostic (CRCD) toolkit is developed and successfully integrated with a standard nucleic acid amplification technique to detect synthesized Human Papillomavirus type 16 (HPV-16) plasmids down to 10 aM sensitivity levels. Furthermore, the CRCD system is applied for ultrasensitive detection of 40 HPV-16 and 40 influenza A viruses in clinical samples, with results consistent with those from PANTHER detection and quantitative real-time polymerase chain reaction (qRT-PCR). In conclusion, this strategy introduces a novel paradigm for engineering crRNA to program Cas12a, which has the potential to revolutionize the use of crRNA in CRISPR-based molecular diagnostics.

Human papillomavirus (HPV) type 16 E6 seroprevalence among men living with HIV without HPV-driven malignancies.

Individuals living with HIV are at a higher risk for developing human papillomavirus-driven oropharyngeal squamous cell carcinoma (HPV+OPSCC). There are no methods for early detection; however, HPV16 E6 antibodies have been identified as a promising early marker. The objective of this study was to evaluate the prevalence of HPV16 E6 antibodies among men living with HIV, with secondary objectives of analyzing clinical and serologic predictors of HPV16 E6 seropositivity. Banked blood specimens from 2,320 men aged 40+ living with HIV in Tennessee were evaluated for the following HPV16 antibodies: L1, E1, E2, E4, E6, E7. HPV16 E6 antibody levels were further categorized as moderate or high. Demographic, clinical, and serologic determinants of HPV16 E6 seropositivity were evaluated using logistic regression. HPV16 L1 antibodies were most common (22.8%), followed by E4 (10.5%), E6 (5.6%), E2 (4.8%), and E7 (4.0%). Of the 130 HPV16 E6 seropositives, 55 (2.4%) had moderate seropositivity and 75 (3.2%) had high. HPV16 E6 seropositive men had nearly 2-fold greater odds of seropositivity against one additional HPV16 E antigen (OR: 1.67 [95% CI: 1.10-2.52]; P=0.015) and over 3-fold greater odds of seroreactivity against two additional HPV16 E antigens (OR: 3.21 [95% CI: 1.40-7.33]; P=0.006). HPV16 E6 seropositivity was not associated with the clinical or demographic factors evaluated. In the largest study to date, HPV16 E6 seroprevalence was elevated compared to prior studies in HIV populations (range: 1.1% to 3.2%) and likely reflects the high incidence of HPV+OPSCC in the southeast region of the United States.

Development and evaluation of a novel E7 multi-epitopic vaccine for human papillomavirus type 16: design, expression, purification, and immunological characterization

BackgroundPersistent infection with high-risk Human papillomavirus (HPV), specifically HPV-16, is the leading cause of cervical cancer. Although preventative vaccines have shown significant efficacy in preventing HPV infection, cervical cancer is a significant public health issue that affects millions of women worldwide. Modern therapeutic approaches, such as peptide vaccines, could be promising and have potential for the treatment of the HPV-infected population.MethodsA HPV16-E7 multi-epitopic vaccine (MEVE7) was designed to comprise potent CD4 + and CD8 + T cell epitopes and optimally expressed in a prokaryotic expression system. Polyclonal antibodies were generated, and their reactivity with immunizing antigen and native protein in E7 expressing cells (TC-1) was assessed by ELISA and immunofluorescent staining, respectively. The efficacy of the vaccine was assessed in a therapeutic animal model of HPV-induced cancer.ResultsOur study revealed that the final construct was successfully expressed in E. coli BL21 (DE3)-gold within 4 h of induction as inclusion bodies. Among the tested solubilization buffers, the buffer with a pH of 12 and containing 2 M urea showed the highest solubilization effect. Polyclonal antibodies directed against the E7 multi-epitope vaccine were able to react strongly with the immunizing antigen and E7-bearing cells (TC-1). Immunization of TC-1 tumor-bearing mice with HPV16-E7, markedly delayed tumor growth and propagation.ConclusionThe poly-epitope vaccine for HPV16-E7, as expressed and purified in this research, is highly immunogenic and capable of triggering E7-specific antibodies, making it a potential therapeutic HPV vaccine. Further research is needed to optimize the vaccination schedule and assess the E7-specific immune cell profile.

Exploring the Role of Lower Genital Tract Microbiota and Cervical–Endometrial Immune Metabolome in Unknown Genesis of Recurrent Pregnancy Loss

Recurrent pregnancy loss (RPL) of unknown genesis is a complex condition with multifactorial origins, including genetic, hormonal, and immunological factors. However, the specific mechanisms underlying endocervical cell proliferation disorders in women with RPL remain inadequately understood, particularly concerning the role of microbiota and viral infections. The aim of this study was to investigate the mechanisms of endocervical cell proliferation disorders in women with RPL of unknown genesis by examining microbiota, human papillomavirus (HPV) typing, and the expression levels of key molecular biological markers, including p16/Ki-67, BCL-2, miR-145, and miR-34a. A prospective observational comparative study was executed on women with RPL and healthy pregnant controls with full ethical approval. Samples were collected for HPV typing and immunocytochemical analysis to evaluate the expression of p16, Ki-67, BCL-2, and the anti-oncogenic microRNAs (miR-145 and miR-34a). The expression of mRNA for the progesterone receptor (PGR-A) was also assessed, alongside local immune status markers, including proinflammatory T-lymphocytes (Th17/Th1) and regulatory CD4+ Tregs. Overexpression of p16, Ki-67, and BCL-2 was observed in 52.5% of women with RPL who had an ASC-US/LSIL cytogram, with the average double expression of p16/Ki-67 being three times higher than in the healthy pregnant group. A significant decrease in PGR-A mRNA expression in the endocervix of women with RPL was noted, accompanied by a dysregulated local immune status characterized by an increased prevalence of Th17/Th1 cells and a reduction in regulatory CD4+ Tregs. Additionally, the expression of miR-145 and miR-34a in the endocervix and endometrium of women with RPL significantly differed from the physiological pregnancy group, particularly in the context of high-risk HPV infection. The findings describe that disorders of endocervical cell proliferation in women with RPL of unknown genesis are associated with overexpression of specific molecular markers, impaired immune regulation, and altered microRNA profiles. These alterations may contribute to the pathophysiology of RPL, highlighting the need for further research into targeted interventions that could improve reproductive outcomes in affected individuals.

Prevalence OF HPV IN a Peruvian Healthcare Network: A Descriptive Cross-Sectional Study.

Human papillomavirus (HPV) infection is a common sexually transmitted infection often associated with cancer development. This study aimed to estimate the prevalence of HPV in women receiving care at the AUNA healthcare network in Peru. We conducted an observational, descriptive, cross-sectional, retrospective study. A de-identified database of HPV-positive women who underwent the BD Onclarity™ HPV Assay between December 2018 and December 2021 at Auna clinics was analyzed. The database contained information regarding age, city, and HPV type. High-risk HPV types were analyzed individually (16, 18, 31, 45, 51, 52) and pooled [P1 (33, 58), P2 (56,59,66), and P3 (35,39,68)]. The study was approved by an independent research ethics committee in Peru. Of 68,714 women included in the study, the HPV prevalence was 14.21% (N = 9765, 95%CI:13.95%-14.47%). The highest prevalence was detected in Piura (16.85%, 95%CI:15.40%-18.38%), where HPV-51, HPV-52, HPV-P1, HPV-P2, and HPV-P3 were most common compared to other Peruvian cities included in the study. In Arequipa, the prevalence was the lowest (13.58%, 95%CI:12.38%-14.85%), but the percentage prevalence of HPV-16 was the highest compared to other cities. The prevalence of multiple HPV infections was 2.88% (N = 1981, 95%CI:2.76%-3.01%), with most of them co-presenting two types of HPV (N = 1522). The most frequent co-occurrences were P2 and P3, P2 and 52, and P2 and 16. Among HPV-positive women, the mean age was 41.31 years (±9.48) and 25.29% were in the 31-35 years group. HPV-P2 was the most frequent in all age groups except in the 65-72 years group, where HPV-P3 was the most common. HPV prevalence was shown to be highest in Piura, with the most prevalent types being HPV-16, HPV-52, and HPV-P2 (HPV-56, -59, -66). HPV infection was found to be more frequent among women in the 31-35 years age group.

A case of warts in toe webs due to HPV type 7: Case report and literature review.

"Butcher's warts" are skin lesions caused by human papillomavirus type 7 (HPV type 7). Another clinically distinctive lesion, "warts in toe webs" (WTW), localized between the toes, has also been reported but remains poorly understood. We report the case of an 84-year-old man with a refractory, cauliflower-like lesion between his toes which was unresponsive to yokuinin and liquid nitrogen cryotherapy. The patient had no history of meat of fish handling. Biopsy revealed papillary thickening of the stratum corneum and vacuolated cells. Polymerase chain reaction and immunohistochemistry analysis confirmed HPV type 7. Treatment modifications, including maintaining a dry interdigital environment, led to resolution within 2 months. Our review of 19 previously reported WTW cases indicates a distinct clinical profile: all cases involved males from Asia, with a prevalence of fungal coinfection. This case indicates the importance of HPV typing for diagnosis and maintaining a dry interdigital environment to enhance treatment outcomes.

Oncoproteins E6/E7 of the human papillomavirus types 16 & 18 synergize in modulating oncogenes and tumor suppressor proteins in colorectal cancer

ABSTRACT Objective Our study presents a novel analysis of the oncogenes and tumor suppressor proteins directly modulated by E6/E7 of high-risk HPV types 16 and 18, in colorectal cancer (CRC). Methods HCT 116 (KRAS mutant) & HT-29 (TP53 mutant) cell models of CRC were transduced with E6/E7 of HPV16 and HPV18, individually and in combination. Further, we utilized a liquid chromatography mass spectrometry (LC-MS/MS) approach to analyze and compare the proteomes of both CRC cell models. Results We generated six stably transduced cell lines. Our data revealed a significantly higher, HPV-induced modulation of oncogenes and tumor suppressor proteins in the TP53 mutant model, as compared to the KRAS mutant model (p ≤ 0.01). Less than 1% of the genes were commonly modulated by HPV, between both models. We also report that HT-29 cells, expressing E6/E7 of both HPV types, significantly reduced the suppression of oncogenes as compared to cells expressing E6/E7 of either HPV types individually (p-value ≤0.00001). Conclusion Our data imply that HPV coinfections leads to the sustenance of a pro-oncogenic environment in CRC. HPV modulates different oncogenes/tumor suppressor proteins in CRC of varying mutational backgrounds, thus highlighting the importance of personalized therapies for such diseases with mutational heterogeneity.

A Qualitative Study of Attitudes Toward HPV Vaccine Recommendation in Otolaryngology Clinics.

The incidence of human papillomavirus (HPV)-related oropharyngeal cancers has increased such that they are now the most prevalent HPV-related cancer. In 2020, the Food and Drug Administration (FDA) expanded the indication for Gardasil-9 to include the prevention of oropharyngeal and other head and neck cancers caused by selected HPV types, but uptake remains low. Otolaryngology office interactions may provide opportunities to increase uptake, given the relevance of HPV to clinical practice. This study explored the feasibility of recommending HPV vaccination in otolaryngology clinics. Participants were recruited between February to June of 2022 from the alumni of the residency and fellowship training programs at the University of Iowa Hospitals and Clinics. Participant interviews comprised open-ended questions pertaining to otolaryngologists' attitudes toward HPV vaccination recommendation. Interview recordings were transcribed, coded, and analyzed for themes. Participants were willing to respond if patients asked about the HPV vaccine, although a common attitude toward vaccine discussions was that they were a pediatrician's responsibility. One barrier to recommending HPV vaccination was providers' concern that discussing the vaccine when not directly relevant to the patient's chief complaint could result in patient frustration. Nevertheless, participants endorsed the feasibility of discussing the vaccine during follow-up visits after the patient's needs had been addressed or via the distribution of educational materials to patients. Otolaryngologists do not currently identify recommending HPV vaccine uptake as their clinical responsibility. While such recommendations may not be feasible in every patient encounter, there could be a role for this in the appropriate clinical scenario. These findings can be used to inform interventions aimed at recommending the vaccine in otolaryngology clinics.

Clinicopathologic Features and Viral Status of Low-risk HPV6 and HPV11-Associated Squamous Cell Carcinoma of the Uterine Cervix and Vulva.

Despite being designated as "noncarcinogenic" human papillomavirus (HPV) types, mono-infection with HPV6 or HPV11 has been found in squamous cell carcinomas (SCCs) at specific sites, including the larynx, penis, anus, and rarely, the lower female genital tract. The association between clinicopathologic features, viral status, and the carcinogenic mechanisms related to these low-risk HPVs remains unclear. The current study characterizes a series of low-risk HPV6 and HPV11-associated SCCs of the uterine cervix (6 cases) and vulva (2 cases). The diagnosis of SCC was made through the identification of stromal invasion in 6 cases. In case 2, the diagnosis of cancer was made after metastases to the sigmoid colon and liver. The patient in case 6 was diagnosed with intramucosal papillary SCC given multiple recurrences. While all tumors displayed a similar verruco-papillary architecture, the cytologic features, and immunostaining patterns suggest 2 groups of lesions: one with high-grade cytology and a high Ki-67 proliferation index (>60% of lesional cells), and the other with low-grade cytology and a low Ki-67 (20% to 30% of lesional cells). The detection of HPV6 in 7 of 8 cases underscores its critical role in carcinogenesis at these anatomic sites. Case 8 represented the only patient who was infected with HPV11 and who had a well-controlled human immunodeficiency virus infection. Correlating with viral status, all cases, except case 7, demonstrated a negative or focal p16 staining pattern. In case 7, despite a block pattern of p16 staining often seen in predicting high-risk HPV, we employed several methods to confirm HPV6 as the sole HPV infection. Although this descriptive study does not establish an etiological mechanism for how HPV6/11 leads to malignant transformation, our results exclude the possibility of viral integration through a quantitative polymerase chain reaction-based analysis of the E2/E6 ratio. Our study highlights and expands upon the clinicopathologic features of a distinct group of low-risk HPV6/11-associated SCCs in the cervix and vulva. Although rare, recognizing this group of lesions is important for pathologists and oncologists, as it provides a basis for guiding appropriate prevention strategies and treatment modalities based on the viral type.

Multi-center evaluation of the Alinity m HR HPV assay with liquid-based cytology cervical specimens in the United States.

Incorporating molecular testing for human papillomavirus (HPV) into the screening of cervical specimens can improve risk stratification and, in turn, patient management. Infection with a high-risk (HR) HPV genotype is associated with greater risk for persistent infection, viral integration, and progression of cervical neoplasia. Current guidelines consider HPV 16 or HPV 18 clinically actionable with referral to colposcopy; however, 12 Other HR HPV genotypes have been associated with cervical cancer risk, suggesting a benefit of extended genotyping. In this multi-center study, we evaluated the performance of the Alinity m HR HPV assay, which reports HPV 16, 18, and 45 individually and aggregates of HPV 31/33/52/58 and HPV 35/39/51/56/59/66, compared with cobas HPV and Aptima HPV assays, across a variety of cytology result categories. A total of 746 de-identified residual cervical specimens, collected as part of routine cervical cancer screening programs, were tested using Alinity m HR HPV and at least one comparator assay. The overall percent agreement was ≥90.7% for results from the Alinity m HR HPV assay and cobas HPV assays and 90.5% for results from the Alinity m HR HPV and Aptima HPV assay. In patients with any abnormal cytology result, Alinity m identified 78 specimens with non-HPV 16/18 results, underscoring the benefit of detecting additional HR HPV genotypes to guide patient management more accurately. Among specimens with normal cytology, Alinity m detected 14 additional specimens with non-HPV 16/18 genotypes. Extended HR HPV testing can provide additional information to triage patients for appropriate testing and follow-up.IMPORTANCEExtended genotyping for high-risk human papillomavirus (HPV) types enhances diagnostic precision by identifying additional oncogenic HPV types beyond 16 and 18 therefore offering a more nuanced risk profile. This more comprehensive detection may aid in identifying persistent infections that are more likely to progress, thereby supporting future risk-based patient management strategies.

Repression of CADM1 transcription by HPV type 18 is mediated by three-dimensional rearrangement of promoter-enhancer interactions.

Upon infection, human papillomavirus (HPV) manipulates host cell gene expression to create an environment that is supportive of a productive and persistent infection. The virus-induced changes to the host cell's transcriptome are thought to contribute to carcinogenesis. Here, we show by RNA-sequencing that oncogenic HPV18 episome replication in primary human foreskin keratinocytes (HFKs) drives host transcriptional changes that are consistent between multiple HFK donors. We have previously shown that HPV18 recruits the host protein CTCF to viral episomes to control the differentiation-dependent viral transcriptional programme. Since CTCF is an important regulator of host cell transcription via coordination of epigenetic boundaries and long-range chromosomal interactions, we hypothesised that HPV18 may also manipulate CTCF to contribute to host transcription reprogramming. Analysis of CTCF binding in the host cell genome by ChIP-Seq revealed that while the total number of CTCF binding sites is not altered by the virus, there are a sub-set of CTCF binding sites that are either enriched or depleted of CTCF. Many of these altered sites are clustered within regulatory elements of differentially expressed genes, including the tumour suppressor gene cell adhesion molecule 1 (CADM1), which supresses epithelial cell growth and invasion. We show that HPV18 establishment results in reduced CTCF binding at the CADM1 promoter and upstream enhancer. Loss of CTCF binding is coincident with epigenetic repression of CADM1, in the absence of CpG hypermethylation, while adjacent genes including the transcriptional regulator ZBTB16 are activated. These data indicate that the CADM1 locus is subject to topological rearrangement following HPV18 establishment. We tested this hypothesis using 4C-Seq (circular chromosome confirmation capture-sequencing) and show that HPV18 establishment causes a loss of long-range chromosomal interactions between the CADM1 transcriptional start site and the upstream transcriptional enhancer. These data show that HPV18 manipulates host cell promoter-enhancer interactions to drive transcriptional reprogramming that may contribute to HPV-induced disease progression.

Vvax001, a Therapeutic Vaccine for Patients with HPV16-positive High-grade Cervical Intraepithelial Neoplasia: a Phase II Trial.

Human papillomavirus (HPV) infection is the major cause of (pre)malignant cervical lesions. We previously demonstrated that Vvax001, a replication-incompetent Semliki Forest virus (SFV) vaccine encoding HPV type 16 (HPV16) E6 and E7, induced potent anti-E6 and -E7 cytotoxic T-cell responses. Here, we investigated the clinical efficacy of Vvax001 in patients with HPV16-positive cervical intraepithelial neoplasia grade 3 (CIN3). Patients with newly diagnosed HPV16-positive CIN3 were eligible for participation. Patients received 3 immunizations of Vvax001 (5x107 infectious particles) at a three-week interval. Up to 19 weeks after the last immunization patients were monitored for regression of CIN3 by colposcopy. A colposcopy-guided biopsy was taken at the last visit and a standard of care loop excision was performed only in case of remaining CIN2/3. Histopathologic response rates, HPV16 clearance, treatment-related adverse events (trAEs), and vaccine-induced immune responses were assessed. A total of 18 patients were enrolled and fully immunized. Colposcopic examination revealed a reduction in CIN3 lesion sizes in 17/18 patients (94%) already evident from 3 weeks onwards after the last immunization. A histopathological complete response (regression to CIN1 or no dysplasia) was observed in 9/18 patients (50%), and HPV16 clearance in 10/16 patients (63%). Vvax001 did not induce clearance of other HPV types. To date, no recurrences have been observed, with a median and longest disease-free survival of 20 and 30 months, respectively. No serious AEs were observed. Treatment with Vvax001 is safe, feasible, and shows preliminary clinical effectiveness in patients with HPV16-associated CIN3 lesions.

First Report of HPV Genotyping and Distribution in People Living with and Without HIV from Iran and the Middle East.

In people living with human immune deficiency (PLHIV), the rates of human papillomavirus (HPV) infection, mixed types, and high-risk (HR) strains increase, while the virus clearance is prevented. Here, we report HPV genotyping in PLHIVs from Iran and the Middle East region for the first time. HPV genotyping in referring individuals from different provinces to our laboratory was evaluated over 2023-2024. For this, the HPV types in specimens were detected through the INNO- LiPA HPV genotyping kit. Statistical analysis was conducted with a 95% confidence interval (95%CI) and P < 0.05. Accordingly, 481 subjects from various provinces participated in this study. The rate of HPV infection was 45.7%, of which 14% were HIV-infected women referred from all provinces. The most prevalent types included 6, 51, and 18, but not 16 HR types. Mixed infections in dually infected women were significantly more than in HPV-infected ones. The HPV+/HIV+ subgroup had the lowest median age. The prevalence of HPV types and mixed infection in PLHIVs was congruent with the previous reports, except for the low rate of type 16 infection, perhaps due to the healthy nature of our subjects. Only HIV+/HPV+ cases' age was similar to the previous reports, perhaps because of sample collection and study designs. Among all factors, age and gender affected the HPV type distribution notably. The current study corroborated the results of many prior reports, demonstrating the considerable impact of HIV status on HPV distribution. The authors recommend implementing a national HPV vaccination and more comprehensive reports of HPV genotyping in PLHIVs.

Human papillomavirus, vaginal microbiota and metagenomics: the interplay between development and progression of cervical cancer.

Persistent infection with oncogenic human papillomavirus (HPV) types, such as HPV 16 or 18, is a major factor in cervical cancer development. However, only a small percentage of infected women develop cancer, indicating that other factors are involved. Emerging evidence links vaginal microbiota with HPV persistence and cancer progression. Alterations in microbial composition, function, and metabolic pathways may contribute to this process. Despite the potential of metagenomics to explore these interactions, studies on the vaginal microbiota's role in cervical cancer are limited. This review systematically examines the relationship between cervical microbiota, HPV, and cervical cancer by analyzing studies from PubMed, EBSCO, and Scopus. We highlight how microbial diversity influences HPV persistence and cancer progression, noting that healthy women typically have lower microbiota diversity and higher Lactobacillus abundance compared to HPV-infected women, who exhibit increased Gardenella, Prevotella, Sneathia, Megasphaera, Streptococcus, and Fusobacterium spp., associated with dysbiosis. We discuss how microbial diversity is associated with HPV persistence and cancer progression, noting that studies suggest healthy women typically have lower microbiota diversity and higher Lactobacillus abundance, while HPV-infected women exhibit increased Gardnerella, Prevotella, Sneathia, Megasphaera, Streptococcus, and Fusobacterium spp., indicative of dysbiosis. Potential markers such as Gardnerella and Prevotella have been identified as potential microbiome biomarkers associated with HPV infection and cervical cancer progression. The review also discusses microbiome-related gene expression changes in cervical cancer patients. However, further research is needed to validate these findings and explore additional microbiome alterations in cancer progression.

Population-based age-period-cohort analysis of declining Human Papillomavirus prevalence.

Most countries in the world have launched human papillomavirus (HPV) vaccination programmes and declining prevalences of HPV are reported. We aimed to disentangle the influences of calendar time, birth cohort and age by analysing HPV prevalences in the population-based cervical screening programme using age-period-cohort modelling. All 836,314 primary HPV-based cervical screening tests from women aged 23-64 between 2014-2023 in the capital region of Sweden were identified in the Swedish National Cervical Screening Registry. The odds ratio of HPV16/18 infection was estimated comparing each birth cohort to the unvaccinated 1984-born using an age-period-cohort model. The impact of changing HPV prevalences on the numbers needed to screen (NNS) to detect and prevent 1 cervical cancer case were calculated. HPV vaccination coverage was 82-83% among women born in 1999-2000. Before 2019 the HPV16/18 prevalence was highest among the youngest women in the screening program. During 2020-2023 the prevalence consistently decreased among the birth cohorts offered organised school-based vaccination. There was a 98% decline in HPV16 prevalence (odds ratio=0.02 [95% CI 0.01-0.04]) and a 99% decline in HPV18 prevalence (odds ratio=0.01 [0.00-0.04]) among the 2000-born compared to the HPV unvaccinated 1984-born. The declining HPV16/18 prevalences resulted in major increases in the NNS to detect and to prevent 1 case of cervical cancer. The declines of HPV16/18 were considerably larger than the vaccination coverage, suggesting herd immunity effects. The changing epidemiology of HPV types impacts screening needs, necessitating updated screening programs.

PRGN-2012 gene therapy in adults with recurrent respiratory papillomatosis: a pivotal phase 1/2 clinical trial.

Recurrent respiratory papillomatosis (RRP) is a rare debilitating condition caused by chronic infection with human papillomavirus (HPV) type 6 or 11. Papillomas develop in the aerodigestive tract, leading to significant voice disturbance and airway obstruction. No systemic treatment currently exists. We aimed to assess the safety and clinical activity of PRGN-2012 in adult patients with RRP treated at the recommended phase 2 dose. This was a single-centre, single-arm, phase 1/2 trial. Adult patients aged 18 years or older with RRP who required three or more interventions in the 1 year before treatment received adjuvant PRGN-2012 on day 1 following surgical debulking of disease, and on days 15, 43, and 85. Primary outcome measure was complete response rate, defined as the percentage of patients who did not require an intervention to control RRP in the 12 months after treatment. Safety outcomes included treatment-related adverse events. This study is registered ClinicalTrials.gov (NCT04724980). From March 16, 2021, to June 1, 2023, 38 patients were enrolled and received the 12-week treatment course. Among the 35 patients treated at the recommended phase 2 dose of 5×1011 particle units, 18 (51%) of 35 patients had a complete response (95% CI 34-69) with the median duration of complete response yet to be reached. Adverse events were mild and included grades 1-2 injection site reaction (34 [97%] of 35), fatigue (28 [80%] of 35), chills (25 [71%] of 35), and fever (24 [69%] of 35). PRGN-2012 treatment resulted in complete response in 51% of the patients treated and was safe. Based on these positive pivotal study results, a biologics license application to the US Food and Drug Administration (FDA) is planned, positioning PRGN-2012 to be an FDA-approved medical treatment for adult patients with RRP. National Institutes of Health.

Rational design of a triple-type HPV53/56/66 vaccine with one preferable base particle incorporating two identified immunodominant sites

The numerous high-risk carcinogenic types of human papillomavirus (HR-HPV) that lack vaccine protection underscore the urgent need to develop broader-spectrum HPV vaccines. This study addresses this need by focusing on HR-HPV types 53, 56, and 66, which are not currently targeted by existing vaccines. It introduces an effective method for their soluble expression, as well as that of their mutants, within an Escherichia coli expression system. Through strategic homologous loop swapping among HPV53, HPV56, and HPV66, we designed twenty double-type chimeric molecules. Comprehensive evaluations identified unique dominant immunogenic loops for each type: the FG loop for HPV53, the HI loop for HPV56, and the DE loop for HPV66, with HPV66 emerging as the optimal chimeric backbone virus-like particle (VLP). By incorporating two identified immunodominant sites into the preferable base particle, the study constructed a triple-type chimera H66-56HI-53FG, which could efficiently self-assemble into VLPs in vitro that closely resembled the wild-type HPV66 VLP and, induced balanced triple-type neutralization titers (~ 3 log unites), as contrast to none observable HPV53 neutralization titer and lower HPV56 titer elicited by the immunization of the wild-type HPV66 alone. This research outlines an amenable way to simultaneously identify immunodominant sites and their preferable particle base context for cross-type vaccine design, thereby offering a paradigm as extending antigenic variety in single particle to broaden vaccine protection coverage.Graphical

Impact of HPV Catch-Up Vaccination on High-Grade Cervical Lesions (CIN2+) Among Women Aged 26-30 in Northern Norway.

Human papillomavirus (HPV) is the primary cause of high-grade cervical lesions and cervical cancer worldwide. In Norway, HPV vaccination was introduced in 2009 for seventh-grade girls and extended through a catch-up program from 2016 to 2019 for women born between 1991 and 1996. This study evaluates the impact of the catch-up vaccination program on the incidence of HPV and high-grade cervical lesions in Troms and Finnmark. We analyzed data from 40,617 women aged 26 to 30 who underwent cervical screening between 2009 and 2023 in Troms and Finnmark, including 1850 women with high-grade cervical lesions (CIN2+) on biopsy. Using linear regression, we assessed trends in high-grade lesion incidence per 1000 screened women and the association between vaccination status and HPV-16/18 incidence. Between 2017 and 2023, the incidence of high-grade cervical lesions significantly decreased: CIN2+ decreased by 33.4%, and CIN3+ decreased by 63.4%. Significant reductions in HPV-16/18-associated high-grade cervical lesions were observed among vaccinated women, with the proportion of CIN2+ cases due to HPV-16 and 18 decreasing from 56.8% in 2017 to 40.7% in 2023, reflecting a 55.8% reduction in the absolute number of cases caused by these high-risk HPV types. Comparing unvaccinated women aged 25-26 in 2016 and vaccinated women in 2023, HPV-16 incidence decreased from 5.1% to 0.1%, and HPV-18 incidence decreased from 3.3% to 0.0%. The catch-up vaccination program significantly reduced the incidence of HPV-16/18 and high-grade cervical lesions in Troms and Finnmark, even with the lower vaccination coverage observed in the catch-up program. These findings demonstrate the effectiveness of HPV vaccination programs in reducing HPV infections and associated cervical lesions.

Nanoparticle-based colorimetric assays for early and rapid screening of the oncogenic HPV variants 16 and 18.

Cervical cancer is predominantly caused by human papillomavirus (HPV), with oncogenic strains HPV 16 and 18 accounting for most cases worldwide. Prompt and precise identification of these high-risk HPV types is essential for enhancing patient outcomes as it enables timely intervention and management. However, the existing HPV detection techniques are time-consuming, expensive, and require highly skilled personnel. This study presents the development and evaluation of a colorimetric nanosensor for the rapid detection of high-risk human papillomavirus (HPV) variants 16 and 18. Gold nanoparticles (AuNPs) were synthesized using an optimized method based on response surface methodology and then functionalized with monoclonal antibodies specific to HPV16-L1 and HPV18-L1 proteins. The nanosensor exhibited a visible color shift from red to violet upon the detection of the target proteins. The analytical validation demonstrated good linearity, sensitivity, precision, accuracy, robustness, and selectivity for detecting recombinant HPV16-L1 and HPV18-L1 proteins. The nanosensor remained stable for at least 90 days when stored at 4 °C. Clinical evaluation of 173 patients, obtained from cervical samples, showed high specificity (77.8 % for HPV16 and 87.3 % for HPV18) and excellent negative predictive value (>96 % for both). Several false-positive results have been associated with other HPV variants or cervical abnormalities. While the sensitivity was limited by the low prevalence of positive samples, the simple, rapid, and equipment-free nature of this colorimetric nanosensor makes it a promising tool for HPV screening, especially in resource-limited settings.

EDUKASI PENCEGAHAN DAN DETEKSI DINI KANKER SERVIKS PADA ANGGOTA PMN (PERMODALAN MEKAR MADANI)

Cervical cancer is a malignant tumor that forms in the cervix. The primary cause of cervical cancer is an infection with oncogenic types of Human Papillomavirus (HPV), particularly types 16 and 18, which lead to abnormal growth in the cervical epithelial tissue. Other risk factors that increase the incidence of cervical cancer include sexual activity with multiple partners, sexually transmitted infections, immune disorders, having many children, low socioeconomic status, and lack of knowledge about reproductive health. The aim of this activity is to enhance participants' knowledge about reproductive organ health as well as the prevention and early detection of cervical cancer. Increasing knowledge can be achieved by providing education on the prevention and early detection of cervical cancer, as well as educating about reproductive health. The results of the educational program showed an increase in knowledge, as reflected in the improved post-test scores.