High-risk Human Papillomavirus Infection Research Articles

The performance of JAM3/PAX1 methylation in the diagnosis of high-grade squamous intraepithelial lesions for women with high-risk HPV infection

ObjectiveTo assess the clinical value of DNA methylation measurement in exfoliated cervical cells for distinguishing high-grade squamous intraepithelial lesions (HSIL) from other cervical abnormalities.MethodsA total of 276 patients were enrolled, and general clinical information was collected. Exfoliated cervical cells were obtained to assess human papillomavirus (HPV) infection, conduct ThinPrep cytology tests (TCT), and measure methylation levels of JAM3 (△CtJ) and PAX1 (△CtP). Logistic regression was performed to identify factors significantly associated with HSIL diagnosis. A conditional inference tree model and the area under the curve (AUC) were employed to evaluate the efficacy of JAM3 and PAX1 methylation in detecting HSIL.ResultsIndependent risk factors for HSIL diagnosis included △CtJ, △CtP, atypical squamous cells of undetermined significance (ASCUS), and HPV16 infection. The conditional inference tree indicated that 96.4% of patients were non-HSIL when △CtJ > 11.66, and 99.1% were non-HSIL when △CtP > 10.97. The diagnostic performance of △CtJ/△CtP surpassed that of TCT/HPV alone. Among six methods, the combination of △CtP, TCT, and high-risk HPV (hr-HPV) testing achieved the highest sensitivity (91.2%), positive predictive value (50.0%), negative predictive value (98.6%), and AUC (0.932).ConclusionIn women with hr-HPV infection, DNA methylation analysis of cervical cytology outperformed traditional TCT or HPV testing. The combination of △CtP with TCT and HPV may offer the most accurate screening approach for HSIL.

Molecular Subtypes of Vulvar Squamous Cell Carcinoma: The Significance of HPV-Independent/p53 Wild Type

Vulvar carcinoma is a rare disease, meeting the criteria for a “rare cancer”, but its incidence is increasing, especially in women <60 years of age. Squamous cell carcinoma (VSCC) accounts for the overwhelming majority of vulvar carcinomas and is the focus of this review. As with many cancers, the increased understanding of molecular events during tumorigenesis has led to the emergence of the molecular subclassification of VSCC, which is subclassified into tumors that arise secondary to high-risk human papillomavirus infection (HPV-associated, or HPVa) and those that arise independently of HPV (HPVi), most commonly in the setting of a chronic inflammatory condition of the vulvar skin. This latter group of HPVi VSCC arises in most cases secondary to mutations in TP53, but recently, attention has focused on the uncommon TP53 wild-type HPVi VSCC. These three molecular subtypes of VSCC (HPVa, HPVi p53 abnormal, and HPVi p53 wild type), as well as their precursor lesions, cannot be diagnosed based on a routine histopathological examination or immunostaining for p53 and p16 as surrogate markers for TP53 mutation and high-risk HPV infection, respectively, are required. The molecular subtyping of VSCC shows high reproducibility and provides important prognostic information. HPVa VSCC has the most favorable prognosis, while HPVi VSCC with TP53 mutations (p53abn) has the worst prognosis, and HPVi VSCC with wild-type TP53 (p53wt) has an intermediate prognosis. In this review, we discuss the evidence supporting this molecular subclassification and its implications for the diagnosis and treatment of VSCC and its precursors.

The Assessment of Knowledge About Cervical Cancer, HPV Vaccinations, and Screening Programs Among Women as an Element of Cervical Cancer Prevention in Poland

Introduction: Cervical cancer is the fourth most commonly diagnosed malignant tumor in women and the fourth leading cause of cancer-related deaths among this population. Since it is asymptomatic in its early stages, preventive screening plays a crucial role in rapid diagnosis. Such screenings are conducted in many countries worldwide, although their popularity varies. Given that nearly all cases of cervical cancer are linked to high-risk human papillomavirus (hrHPV) infection, vaccination against this virus could lead to a significant reduction in cancer incidence. It should be noted that the level of vaccination coverage against hrHPV varies significantly between countries, ranging from a few percent to over 90%. Globally, the vaccination coverage of the target population is estimated at only a few percent. Methods: This study was conducted using a proprietary, anonymous online questionnaire comprising 24 questions addressing various aspects of cervical cancer prevention. The newly designed questionnaire comprised 19 primary questions and 5 metric questions. The collected data were subjected to descriptive and statistical analysis. Results: The majority of respondents reported regularly participating in cervical cytology screening and gynecological visits. Non-participation in these screenings was primarily reported by younger respondents, not all of whom had indications for undergoing such examinations. Only 14% of the women surveyed had been vaccinated against hrHPV. However, it should be noted that, as the surveyed women were not covered by the relatively recently introduced vaccination program, they received their vaccinations through local programs conducted by certain cities or through private healthcare services. The respondents’ primary sources of information on cervical cancer are the internet and medical personnel. Conclusions: The level of knowledge among the women surveyed regarding cervical cancer prevention was satisfactory, though improvement is needed in some areas. Despite relatively good awareness of HPV’s role in cervical cancer development, the popularity of HPV vaccination remains unsatisfactory. The results should be interpreted with caution due to the small study group.

Prevalence of HPV infection in the general population of young and adult males in Italy.

The most prevalent sexually transmitted disease in the world has the human papillomavirus (HPV) as its etiological agent. To evaluate the prevalence of previous and actual HPV infection and the clinical manifestations in unselected males. A total of 718 males participating to a surveillance program were asked to complete a study visit at our unit, including semen collection, balanopreputial sulcus swab, and blood collection for total anti-HPV immunoglobulin G (IgG). When HPV-DNA was detected, we performed HPV fluorescence in situ hybridization, oral and anal swab, and penoscopy. Because previous studies demonstrated a very high risk for HPV infection in subjects with history of HPV-induced lesions, with a partner with diagnosed HPV infection or reporting couple infertility or sexual promiscuity and an increase of the risk in males having sex with males, in subjects with unprotected sexual intercourses or in heavy smokers, patients were therefore stratified according to the presence of these known risk factors (RFs). Actual HPV infection was detected in 401/718 subjects (55.85%). Oral HPV-DNA was reported in 80 subjects and anal HPV infection in 52 subjects. Anti-HPV IgG antibodies have been detected in 288 subjects. The overall prevalence of HPV exposition, considering actual and/or previous infection was 77.99%. Among infected men, high-risk HPV genotypes were detected in 66.08%. A total of 514 subjects were considered as the RF population, while 150 were classified in the non-RF population. There was a significantly higher prevalence of condylomatosis (odds ratio [OR] 4.07) and of seminal infection (OR 6.22) in the RF group. These data represent an alert for the healthcare system to perform informative and screening campaigns for HPV infection in males and to promote HPV vaccination both in young people and for adult males with RF for HPV infections.

Recent advances in HPV biotechnology: understanding host-virus interactions and cancer progression – a review

Cervical cancer ranks as the fourth most common cancer among women globally, posing a significant mortality risk. Persistent infection with high-risk human papillomavirus (HPV) is the primary instigator of cervical cancer development, often alongside coinfection with other viruses, precipitating various malignancies. This study aimed to explore recent biotechnological advances in understanding HPV infection dynamics, host interactions, and its role in oncogenesis. The gathered data shed light on HPV biology, host-virus interplay, viral coinfections, and cellular transformations leading to HPV-associated cancers. Recent years have seen the introduction of diverse vaccination strategies, including live attenuated, subunit, and DNA-based vaccines, complemented by innovative nanotechnology and plant-based products. Despite rich data addressing research inquiries, urgent calls echo for the implementation of contemporary screening and therapeutic modalities at clinical levels. Moreover, extensive public awareness campaigns are imperative to alleviate the burden of HPV-related diseases, emphasizing the necessity for proactive intervention strategies in combating this global health challenge.

A Preclinical Immunogenicity Study of the Recombinant Human Papillomavirus Nine-Valent Virus-like Particle Vaccine

Background: Cervical cancer is associated with persistent infection of high-risk human papillomaviruses (HPVs). Prophylactic HPV vaccines have been recommended and have significant efficacy in preventing cervical cancer. Multivalent HPV vaccines have a better preventative effect on HPV-related diseases. However, there is currently only one nine-valent HPV vaccine on the market: Gardasil® 9. The development of new HPV vaccines is still urgent in order to achieve the goal of eliminating cervical cancer as proposed by the WHO. Methods: In this study, we developed a nine-valent recombinant HPV virus-like particle (VLP) vaccine (HPV-9 vaccine) containing HPV type 6, 11, 16, 18, 31, 33, 45, 52, and 58 antigens, with an adjuvant of aluminum phosphate (AlPO4). The type-specific L1 proteins were recombinantly expressed using Pichia pastoris, followed by self-assembly into VLPs. Immunogenicity studies of the HPV-9 vaccine were performed using rodents (mice and rats) and non-human primates (macaques) as animal models. Results: Immunogenicity studies showed that the HPV-9 vaccine is able to elicit a robust and long-lasting neutralizing antibody response in rodents (mice and rats) and non-human primates (cynomolgus macaque) models. The HPV-9 vaccine shows immunogenicity comparable to that of Walrinvax® and Gardasil® 9. Conclusions: In summary, this study provides a comprehensive investigation of the immunogenicity of the HPV-9 vaccine, including its immune persistence. These findings, derived from using models of diverse animal species, contribute valuable insights into the potential efficacy of the vaccine candidate in clinical settings.

Triage performance of DNA methylation for women with high-risk human papillomavirus infection.

DNA methylation is a promising biomarker for cervical cancer screening. This study aimed to validate the triage performance of cytological DNA methylation for detecting cervical intraepithelial neoplasia of grade 3 or worse (CIN3+) in women with high-risk human papillomavirus (hrHPV) infection from a large prospective cohort undergoing opportunistic screening in China (METHY3). The triage performance for detecting CIN3+ lesions was compared between HPV16/18 genotyping, a liquid-based cytology (LBC) test, and the PAX1 and JAM3 methylation (PAX1m/JAM3m) test according to cervical pathologic outcomes. Among the 4394 women infected with hrHPV, 1105 had definitive cervical histological findings that were analyzed. For detecting CIN3+, the specificity of HPV16/18(+), the LBC result of ≥atypical squamous cells of undetermined significance (ASCUS), and PAX1m/JAM3m(+) was 66.4%, 23.9%, and 89.6%, respectively, with odds ratios of 4.24 (95% confidence interval [CI], 2.85-6.40), 4.44 (2.27-10.1), and 18.5 (12.1-28.7) (P < .001), respectively. PAX1m/JAM3m(+) had the highest area under the receiver operating characteristic curve (0.790, 95% CI, 0.747-0.832) in the whole cohort and in women of various ages. PAX1m/JAM3m (+) was detected in all patients with cancer (n = 28). Compared with HPV16/18 genotyping and the LBC test, PAX1m/JAM3m testing reduced referrals to colposcopy by 20.64 percentage points and 61.18 percentage points, respectively. PAX1 m /JAM3 m testing is highly specific for detecting CIN3+. As a triage biomarker, it is superior to HPV 16/18 genotyping and LBC testing for women with hrHPV infection.

Analysis of the Impact of Pharmacological Intervention on the Outcome of High-Risk HPV Infections

This study aims to evaluate the clinical effectiveness of different drug treatment regimens for cervical high-risk human papillomavirus (HR-HPV) infection. Through literature review and randomized group experiment design, the study compares the HPV-DNA clearance rate, TCT results, and colposcopic biopsy findings among the control group, interferon group, and combination treatment group after six months of treatment. The results indicate that recombinant human interferon-2b vaginal effervescent tablets can effectively improve HPV clearance and reduce the risk of lesion progression, although individual responses to treatment vary. Combination therapy may enhance treatment efficacy by boosting immune response. The study also explores the relationship between drug treatment, viral load, cervical lesions, and vaginal microecology, providing scientific support for clinical medication decisions and offering a detailed analysis of the role of pharmacological intervention in the prognosis of HR-HPV infections.

Natural History of High-Risk Human Papillomavirus in Kenyan and South African Women: Implications for Vaccination Campaigns and Cervical Cancer Screening Programs.

Human papillomavirus (HPV) vaccines and DNA testing roll out in resource-constrained settings. We evaluated the natural history of HPV infections in African women to contribute to normative guidance. Women aged 16 to 35 years were enrolled from 3 sites in South Africa and Kenya and followed quarterly for 18 months. A subset was recalled 5 years postenrollment, when Papanicolaou smears were conducted. Endocervical swabs were tested for 36 HPV genotypes by HPV Direct Flow. Logistic regression models identified correlations between demographic, biological, or behavioral factors and baseline high-risk HPV (HR-HPV). At enrollment, 158 of 311 women (median age, 23 years; IQR, 20-27) had at least 1 HR-HPV genotype. HPV-52 (13.5%), HPV-16 (9.5%), HPV-58 (9.0%), HPV-18 (8.4%), and HPV-35 (8.4%) were most common. Coinfection with low-risk HPVs (odds ratio, 2.65; 95% CI, 1.59-4.45) were associated with HR-HPV positivity, while reported condom use (odds ratio, 0.57; 95% CI, .34-.98) and older age were protective. Of women with HR-HPV at enrollment, 87.3% cleared at least 1 HR-HPV infection over 18 months and 64.6% cleared all such infections. Few (1.9%) had evidence of high-grade cervical abnormalities, among which HPV-35 was the most prevalent during the study. The high prevalence of HR-HPV emphasizes that HPV vaccination, screening, and testing campaigns in Africa are important. Nonvaccine HPV-35 was as common as HPV-18, suggesting the need to supplement current vaccines with this genotype. HR-HPV clearance was also common, highlighting that clear messaging is needed from health care providers to patients while discussing HPV DNA testing results.

Glycan-induced structural activation softens the human papillomavirus capsid for entry through reduction of intercapsomere flexibility

High-risk human papillomaviruses (HPVs) cause various cancers. While type-specific prophylactic vaccines are available, additional anti-viral strategies are highly desirable. Initial HPV cell entry involves receptor-switching induced by structural capsid modifications. These modifications are initiated by interactions with cellular heparan sulphates (HS), however, their molecular nature and functional consequences remain elusive. Combining virological assays with hydrogen/deuterium exchange mass spectrometry, and atomic force microscopy, we investigate the effect of capsid-HS binding and structural activation. We show how HS-induced structural activation requires a minimal HS-chain length and simultaneous engagement of several binding sites by a single HS molecule. This engagement introduces a pincer-like force that stabilizes the capsid in a conformation with extended capsomer linkers. It results in capsid enlargement and softening, thereby likely facilitating L1 proteolytic cleavage and subsequent L2-externalization, as needed for cell entry. Our data supports the further devising of prophylactic strategies against HPV infections.

The Effect of Interventions Based on the Information-Motivation-Behavioral Skills Model on the Human Papillomavirus Vaccination Rate Among 11-13-Year-Old Girls in Central and Western China: Protocol for a Randomized Controlled Trial.

Persistent infection of high-risk human papillomavirus (HPV) can lead to cervical intraepithelial neoplasia, cervical cancer, and even death. HPV vaccination for girls aged 9-14 years can effectively prevent the occurrence of cervical cancer. Some Chinese provinces and cities have launched free HPV vaccination programs for school-age girls; however, due to the lack of supportive government policies, the high price and supply shortage of HPV vaccines, and vaccine hesitancy, some parents refuse to vaccinate their daughters. This protocol reports the design of a randomized controlled trial (RCT) aiming to explore the efficacy of a digital HPV vaccination education intervention based on the information-motivation-behavioral skills (IMB) model in improving the HPV vaccination rate among 11-13-year-old girls in central and western China. A multicenter intervention study based on an online applet will be conducted in December 2024, and about 750 eligible parents of 11-13-year-old girls will be assigned in a 1:1 ratio to an intervention group receiving 7-day digital HPV vaccination education based on the IMB model or a control group using non-HPV publicity materials. Free HPV vaccination pilot projects will be carried out among this population by our research team in central and western China (some parents might refuse to vaccinate their daughters). All participants will be asked to complete online questionnaires at baseline; postintervention; and 1 week, 1 month, and 3 months after the intervention. The primary outcome of this study will be receipt of the first HPV vaccination within 3 months. Data will be analyzed based on an intention-to-treat approach, and Stata 16.0 will be used for statistical analysis. This study aims to improve the HPV vaccination rate among 11-13-year-old girls and will examine the impact of a digital HPV vaccination education intervention based on the IMB model. The findings of this study may offer promising intervention measures for HPV vaccine hesitancy in low-health-resource areas in the future. Chinese Clinical Trial Registry, ChiCTR2300067402; https://tinyurl.com/v5zt4hc9. PRR1-10.2196/58873.

Human umbilical cord mesenchymal stem cells small extracellular vesicles-derived miR-370-3p inhibits cervical precancerous lesions by targeting DHCR24

Abstract Background Cervical cancer is often caused by persistent high-risk human papillomavirus (HPV) infection, causing precancerous lesions. Human umbilical cord mesenchymal stem cells-derived small extracellular vesicles (hucMSC-sEV) exhibit diverse effects on tumors. This study investigates hucMSC-sEV, the impact and mechanisms on HPV-positive cervical precancerous lesion cells to provide new treatment insights. Materials and Methods We previously obtained hucMSC and hucMSC-sEV. In vitro experiments evaluated hucMSC-sEV effects on the proliferation and migration of S12 cells (derived from cervical precancerous lesions). Bioinformatics identified key microRNA components, and their impact on S12 cell proliferation and migration was investigated. The target gene of the microRNA component was predicted and confirmed via bioinformatics and dual-luciferase reporter assays. Lentiviral systems overexpressed target gene in S12 cells to examine the effects on microRNA impacts. SH-42 inhibitor was used to investigate target gene treatment potential. Immunohistochemistry assessed target gene expression in cervical precancerous lesions tissue. Results hucMSC-sEV significantly inhibited S12 cell proliferation and migration. Bioinformatics identified miR-370-3p as an effective cargo, which also suppressed S12 cell proliferation and migration. miR-370-3p was confirmed targeting DHCR24 (24-Dehydrocholesterol Reductase). DHCR24 overexpression reversed miR-370-3p’s inhibitory effects, while SH-42 counteracted DHCR24 overexpression’s promoting effects. Clinical specimen analysis supported these findings, demonstrating a positive correlation between DHCR24 protein expression and cervical precancerous lesions’ progression. Conclusions hucMSC-sEV inhibits S12 cell proliferation and migration, mediated by miR-370-3p targeting DHCR24 to regulate cellular cholesterol content. DHCR24 inhibition reduces the cholesterol level and cell functions, suggesting its potential as a therapeutic target in cervical precancerous lesions.

Modulation of metabolic pathways and EndMT inhibition by a traditional Chinese herbal formula in the treatment of high-risk infections.

Herbal products have long been utilized as remedies for various disease conditions, including infections. This study investigates the therapeutic mechanism of a traditional Chinese herbal combination in treating high-risk HPV infections. The herbal formula was prepared using common herbs: dry Millettia speciosa, Guanzhong (a spermatophyte), Sarsaparilla, White Fruit, and Cockscomb Flower. Eight female patients diagnosed with high-risk HPV were enrolled from January to September 2023 at Shenzhen Hospital of Beijing University of Traditional Chinese Medicine. Cervicovaginal secretions were collected before and after treatment with the herbal remedy and analyzed using non-targeted metabolomics techniques. In vitro studies were conducted using HeLa cells to determine the optimal effective concentration of the remedy, assessed via the CCK8 method. The proliferation and migration of HeLa cells were evaluated using Transwell assays. Quantitative PCR was employed to measure mRNA levels of endothelial-to-mesenchymal transition (EndMT) markers, including VE-Cadherin, eNOS, α-SMA, and Snail. In vivo, significant alterations in cervicovaginal secretion metabolites post-treatment were observed through PCA, OPLS-DA, and volcano plot analyses. KEGG enrichment analysis highlighted crucial signaling pathways such as arginine and proline metabolism, purine metabolism, glycerophospholipid metabolism, and phenylalanine metabolism, indicating the herbal combination's systemic effects on patients. In vitro experiments demonstrated a dose-dependent reduction in HeLa cell proliferation and migration, confirmed by scratch and Transwell assays. Additionally, qPCR analysis revealed down-regulation of α-SMA and Snail, and up-regulation of VE-Cadherin and eNOS, suggesting inhibition of EndMT in HeLa cells. The traditional Chinese herbal combination modulates key metabolic pathways in vivo and inhibits EndMT in vitro, while reducing HeLa cell proliferation and migration. These findings highlight its potential as a therapeutic approach for managing HPV infections, bridging traditional practices with scientific research.

Prediction of high-grade cervical precancerous abnormalities: The role of personal factors, vaginal microflora, sexually transmitted infections, and high-risk human papillomavirus.

High-risk human papillomavirus infection (HR-HPV) is necessary but not the only factor needed to develop cervical cancer. It is essential to estimate cervical cancer development risk in the population of high-risk HPV-positive women and to avoid unnecessary examinations and treatment in low-risk individuals. The study aimed to identify associations between different personal factors, vaginal microflora, sexually transmitted, high-risk HPV infection, and various degrees of cervical precancerous lesions. A study was performed in 2016-2020. The study group consisted of 112 patients with abnormal cervical cytology results referred for colposcopic examination. 120 women who came for a routine gynecological check-up were included in the control group. Material from the cervix and upper vaginal fornix was taken for pH measurement, wet mount microscopy, testing the six most common high-risk HPV DNA types (16/18, 31, 33, 45, 58), HPV E6/E7 mRNA, and 7 genital infections-C. trachomatis, N. gonorrhea, T. vaginalis, M. hominis, M. genitalium, U. urealyticum, U. parvum. Results showed that women with all grades of cervical intraepithelial neoplasia (CIN) more often were smokers, had increased vaginal pH levels, and had positive HR-HPV DNA and HR HPV E6/E7 mRNA expression. Abnormal vaginal microflora, especially types associated with aerobic vaginitis, and M. hominis were significantly more often found in women with CIN2+. The presence of C.trachomatis, U. parvum, and U.urealyticum did not differ between the groups. The most important factors independently associated with CIN2+ were positive high-risk HPV E6/E7 mRNA expression (OR 59.4, 95% CI 14.84-237.51), and positive high-risk HPV DNA (OR 3.9, 95% CI 1.16-13.23). Higher education level was associated with reduced risk of CIN2+ (OR 0.2, 95% CI 0.07-0.71). In conclusion, this study reports HR-HPV DNA of the most common six types and E6/E7 mRNA positivity as the most significant factors associated with CIN2+ lesions and higher education related to lower risk of high-grade cervical lesions.

Human papillomavirus and male infertility correlation analysis following World Health Organization 2021 guidelines

Male infertility is a complex issue influenced by multiple environmental and pathological factors. In this context, the impact of Human papillomavirus (HPV) infection on male fertility remains controversial. The introduction of new WHO 2021 evaluation criteria, included in the 6th ed. of Laboratory Manual for the examination and processing of human semen, i.e. DNA fragmentation index (DFI), slow and rapid progressive motility, could provide additional information about this correlation. 121 semen samples of male partners of HPV-positive women attending In Vitro Fertilization (IVF) were evaluated following WHO 2021 and HPV-DNA test. Comparing HPV-negative and positive samples for rapid and slow progressive motility showed significantly different results (p = 0.0018, p = 0.0004), contrary to what was observed for total progressive motility. Regarding sperm DFI, only high-risk HPV infections affected DNA integrity. In addition, the correlation between the different semen parameters revealed a significant correlation between midpiece morphological defects and rapid progressive motility in the HPV-positive group (rho = 0.43, p = 0.0006). In conclusion, WHO 2021 provides additional information regarding HPV’s impact on seminal parameters. The correlation between HPV positivity, midpiece defects and a higher rapid progressive motility opens new research perspectives that may help unravel the issues surrounding the role of HPV in compromising sperm quality.

Cervical precancer screening using self-sampling, HPV DNA testing, and mobile colposcopy in a hard-to-reach community in Ghana: a pilot study

BackgroundThe World Health Organization has set ambitious goals to eliminate cervical cancer, necessitating evidence on increasing coverage and access to screening and treatment in high-burden areas. We implemented a pilot program to assess the feasibility of obtaining self-collected specimens for high-risk human papillomavirus (hr-HPV) testing in Nzulezo stilt village, a hard-to-reach community in Ghana, and inviting only hr-HPV-positive women to a central location for colposcopy and possible treatment. Subsequently, this study aimed to investigate the prevalence of hr-HPV infection and cervical lesions among the women and to explore factors potentially associated with hr-HPV infection among them.MethodsThis pilot community-based cross-sectional study utilized data from screening sessions held from 2 to 20 November 2021 with specimens collected by participants using Evalyn brushes. HPV DNA testing was performed using the Sansure MA-6000 platform, while visual inspection utilized the Enhanced Visual Assessment (EVA) mobile colposcope. Univariate and multivariable nominal logistic regression was employed to explore factors associated with hr-HPV positivity.ResultsAmong 100 women screened (mean age, 43.6 ± 14.5 years), the overall hr-HPV prevalence rate was 39.0% (95% CI, 29.4–49.3). The prevalence rates of hr-HPV genotypes were stratified as follows: HPV16–8.0% (95% CI, 3.5–15.2), HPV18–5.0% (95% CI, 1.6–11.2), and other genotype(s) – 31.0% (95% CI, 22.1–41.0). Single-genotype infections with HPV16 and HPV18 were found in 4.0% (95% CI, 1.1–9.9) and 3.0% (95% CI, 0.6–8.5) of women, respectively. Mixed infections were observed in 1.0% (95% CI, 0.0–5.4) for HPV16 + 18, 3.0% (95% CI, 0.6–8.5) for HPV16 + other type(s), and 1.0% (95% CI, 0.0–5.4) for HPV18 + other type(s). The prevalence of cervical lesions among hr-HPV-positive women screened via colposcopy was 11.4% (95% CI, 3.2–26.7). In the multivariable model, reliance on other sources for medical bill payment was associated with hr-HPV infection (aOR, 0.20; 95% CI, 0.04–0.93), whereas age was not (aOR, 1.02; 95% CI, 0.99–1.05).ConclusionsA high hr-HPV infection prevalence was recorded among the women. Utilizing technologies such as self-sampling, HPV DNA testing, and mobile colposcopy enables screening and treatment in remote and hard-to-reach communities where access to cervical cancer screening and treatment would otherwise be limited. Further research is warranted to assess the value and scalability of this approach in similar remote areas and its potential implementation in future programs.

Prevalence, Characteristics, and Distribution of Human Papillomavirus According to Age and HIV Status in Women of Eastern Cape Province, South Africa.

Human papillomavirus (HPV) is a sexually transmitted infection associated with the development of cervical cancer. This study investigated cervical HPV prevalence, characteristics, and distribution according to age and human immunodeficiency virus (HIV) status among women attending a public community health facility in the Eastern Cape Province of South Africa. A total of 325 participants (aged 18 to 60) visiting a community health facility for any reason were recruited. Cervical HPV infection was detected using the Seegene Anyplex™ II HPV28 assay (Seegene Inc., Seoul, South Korea). Overall HPV prevalence was 65.2% (95% CI: 59.9-70.2%), with the highest prevalence of 80.9% (95% CI: 67.2-89.8%) observed in the 18-25-year-old age group and the lowest prevalence of 46.3% (95% CI: 35.8-57.1%) in the 46-60-year-old age group. HR-HPV infection was found to decrease with increasing age (p < 0.001) in the overall population and according to HIV status. In contrast, LR-HPV infection was found to significantly decrease with age among HIV-negative women (p = 0.001) but not for the overall population and HIV-positive women. A proportion of 12.9% were infected with one or more HPV types covered by the Cervarix® HPV vaccine (HPV-16 and/or -18), 18.8% (by those covered by Gardasil®4 (HPV-6, -11, -16 and/or -18), and 42.2% by those covered by Gardasil®9 (HPV-6, -11, -16, -18, -31, -33, -45, -52 and/or -58). The alpha-9 HPV species was the most dominant species (40.6%), followed by the alpha-7 species (29.8%). High overall HPV, HR-HPV, and alpha-9 species prevalence were observed among the women attending the public health facility. These findings contribute to the limited HPV distribution data among the Eastern Cape women, which could be used to improve HPV-related policy and assess the effectiveness of the HPV vaccination.

Epidemiological and typing features of HPV co-infections in MSM with mpox: A hospital-based prospective study

ObjectivesRecent mpox outbreaks highlight diverse transmission modes, with sexual behavior prominent in China's IIb strain. Nevertheless, despite HPV being a common sexually transmitted pathogen, there is a paucity of research into its coexistence and genotype distribution within this patients population. MethodsWe conducted a study at the Third People's Hospital of Shenzhen from May to September 2023. We collected information on mpox patients, including their sociodemographic and clinical characteristics. Anal swabs were collected for HPV genotyping. ResultsAmong 73 MSM mpox cases, HIV positivity was 56.2 % (41/73) and HPV positivity 80.4 % (41/51). Multiple HPV infections were prevalent (56.9 %, 29/51), especially among HIV-positive (93 %, 27/29). HPV16 (29.3 %, 12/41) was the most common high-risk genotype, followed by HPV59 (26.8 %, 10/41), HPV42 (19.5 %, 8/41), HPV6 (14.6 %, 6/41), and HPV54 (14.6 %, 6/41). HPV infection was significantly associated with HIV infection (p = 0.001). Additionally, HIV infection (p = 0.001) and PCR-detected positive sites for mpox (p = 0.047) were associated with high-risk HPV infection. ConclusionsIn this study, most of the mpox patients were found to be infected with HPV, mostly with high-risk types and multiple infections. Therefore, it is strongly recommended that mpox-infected individuals intensify HPV-related screening, prevention, and treatment measures.

The anti-tumor efficacy of a recombinant oncolytic herpes simplex virus mediated CRISPR/Cas9 delivery targeting in HPV16-positive cervical cancer

Cervical cancer, often driven by high-risk human papillomavirus (HPV) infections such as HPV16 or HPV18, remains a leading cause of cancer-related deaths. HPV16, found in about 90% of cervical cancer patients, harbors key oncogenic related genes (E6, E7, E2, E5) and an upstream regulatory region (URR) that contribute to cancer progression. This study introduces a novel approach using a recombinant oncolytic herpes simplex virus type 1 (HSV-1) named SONC103, armed with a CRISPR/Cas9 gene editing system. The aim was to target and disrupt integrated HPV16 genes in cervical cancer cells. Results demonstrated SONC103's capability to specifically and effectively knock down HPV16 oncogenes, thereby reducing cell proliferation and promoting apoptosis. Analyses further revealed loss of HPV16 DNA probes in infected cells' chromosomes, significant regulation of cellular processes related to tumor apoptosis, and downregulation of E6/E7 oncoproteins while increasing tumor suppressor proteins P53 and pRB. Notably, SONC103 exhibited substantial inhibition of tumor growth in a murine xenograft cervical cancer model. This study showcases the potential of the recombinant oncolytic HSV-1 virus (SONC103) in combating HPV16-positive cervical cancer by targeting oncogenes and facilitating oncolysis.

The Potential Impact of a Single-Dose HPV Vaccination Schedule on Cervical Cancer Outcomes in Kenya: A Mathematical Modelling and Health Economic Analysis.

Background: Human Papillomavirus (HPV) is the primary cause of cervical cancer. Single-dose HPV vaccination can effectively prevent high-risk HPV infection that causes cervical cancer and accelerate progress toward achieving cervical cancer elimination goals. We modelled the potential impact of adopting single-dose HPV vaccination strategies on health and economic outcomes in Kenya, where a two-dose schedule is the current standard. Methods: Using a validated compartmental transmission model of HPV and HIV in Kenya, we evaluated the costs from the payer's perspective to vaccinate girls by age 10 with either one or two doses and increasing coverage levels (0%, 70%, 77%, 90%). Additionally, we modelled single-dose strategies supplemented with either catch-up vaccination of adolescent girls and young women or vaccination for all by age 10, funded with the first five-years of cost savings of switching from a two- to one-dose schedule. Costs and outcomes were discounted at 3% annually, and incremental cost-effectiveness ratios (ICERs) were calculated per disability-adjusted-life-year (DALY) averted. Results: All one-dose and the two-dose 90% coverage strategies were on the efficiency frontier, dominating the remaining two-dose strategies. The two-dose 90% coverage strategy had a substantially higher ICER (US$6508.80/DALY averted) than the one-dose 90% coverage (US$197.44/DALY averted). Transitioning from a two- to one-dose schedule could result in US$21.4 Million saved over the first five years, which could potentially fund 2.75 million supplemental HPV vaccinations. With this re-investment, all two-dose HPV vaccination scenarios would be dominated. The greatest DALYs were averted with the single-dose HPV vaccination schedule at 90% coverage supplemented with catch-up for 11-24-year-old girls, which had an ICER of US$78.73/DALYs averted. Conclusions: Considering the logistical and cost burdens of a two-dose schedule, a one-dose schedule for girls by age 10 would generate savings that could be leveraged for catch-up vaccination for older girls and accelerate cervical cancer elimination in Kenya.