HPV Infection Research Articles

HPV specificity and multiple infections and association with cervical cytology in Chongqing, China: a cross-sectional study

BackgroundIt is important to assess the relationship between specific HPV genotype or multiple infection and cervical cytology. The protection provided by the HPV vaccine is type-specific, and the epidemiology feature of coinfections needs to be investigated. The aim is to provide baseline information for developing HPV vaccination and management of HPV-positive populations in the region.MethodsA total of 3649 HPV-positive women were collected from 25,572 women who underwent 15 HR-HPV genotypes and ThinPrep cytologic test (TCT) results. Logistic regression was used to determine the correlation between the risk of cytology abnormalities and specific HPV infection. We calculated odds ratios (ORs) to assess coinfection patterns for the common two-type HPV infections. chi-squared test was used to estimate the relationship between single or multiple HPV (divided into species groups) infection and cytology results.ResultsThe results showed there was a positive correlation between HPV16 (OR = 4.742; 95% CI 3.063–7.342) and HPV33 (OR = 4.361; 95% CI 2.307–8.243) infection and HSIL positive. There was a positive correlation between HPV66 (OR = 2.445; 95% CI 1.579–3.787), HPV51 (OR = 1.651; 95% CI 1.086–2.510) and HPV58(OR = 1.661; 95% CI 1.166–2.366) infection and LSIL. Multiple HPV infections with α9 species (OR = 1.995; 95% CI 1.101–3.616) were associated with a higher risk of high-grade intraepithelial lesions (HSIL) compared with single HPV infection. There were positive correlations between HPV66 and HPV56 (α6) (OR = 3.321; 95% CI 2.329–4.735) and HPV39 and HPV68 (α7). (OR = 1.677; 95% CI 1.127–2.495). There were negative correlations between HPV52, 58, 16 and the other HPV gene subtypes.ConclusionHPV33 may be equally managed with HPV16. The management of multiple infections with α9 may be strengthened. The 9-valent vaccine may provide better protection for the population in Chongqing currently. The development of future vaccines against HPV51 and HPV66 may be considered in this region.

Uncommon high distribution of HPV-16, HPV-54, and HPV-56 in female referred to a laboratory in Karaj, Iran: indications of a paradigm shift in HPV genotypes?

BackgroundHuman papillomavirus (HPV) is among the leading cause of sexually transmitted infections, particularly prevalent among sexually active individuals. While many HPV infections clear up over time, some may progress to various cancers such as anal cancer, cervical cancer and, vaginal cancer. This study examines the prevalence of different HPV genotypes, classified as high-risk (HR) and low-risk (LR), among females of various age groups who visited the laboratory in Karaj.Material and methodsGenital specimens were gathered from the individuals involved in the study and subjected to DNA extraction (DNA/RNA extraction AmpliSense, Moscow, Russia) followed by amplification using Real-Time PCR. HR- and LR-HPV genotypes were identified using the GenoFlow HPV Array test kit (GenoFlow; DiagCor Bioscience, Hong Kong) and homemade HPV genotyping kit. Demographic information such as age, was examined alongside statistical virological data.ResultsOverall, 367 (17%) out of the 2109 (100%) female cases tested positive for HPV. Among these, 219 (46.2%) were classified as low-risk, 44 (9.3%) as potentially high-risk, and 211 (44.5%) as high-risk. The highest percentage of positive test results was detected in individuals under 30 years old (35%) and those aged 40–50 (18%). Individuals in the < 30 age group were primarily infected with HR genotypes. The most commonly identified genotypes overall were HPV-16 (11.7%), HPV-54 (10.3%), HPV-56 (8.4%), HPV-40 (8.1%). The lowest frequency was observed for HPV-70, HPV-71, HPV-82, and HPV-90, each recorded in only a single case.ConclusionOur results highlight the notable occurrence of HPV among females who visited the laboratory in Karaj, especially in the < 30 age group. Identifying HPV-16 as the most prevalent genotype in our examination highlights the necessity of tailored interventions for specific age ranges. While HPV-16 is covered by vaccination programs, HPV-54 and HPV-56 are not, emphasizing the need for effective screening and preventive plans to manage the consequences of HPV-related diseases in future.

HPV vaccine behaviors and intentions among a diverse sample of women aged 27-45 years: implications for shared clinical decision-making

BackgroundThe Advisory Committee on Immunization Practices issued a shared clinical decision-making (SCDM) recommendation for HPV vaccination in persons aged 27–45. Since expanded eligibility for the vaccine was issued, little information has been available about HPV vaccine behaviors and intentions among women in this age group.MethodsWe conducted a cross-sectional online survey among women aged 27–45 years recruited through a Qualtrics™ respondent panel (N = 324) to answer the following questions (1) What is the prevalence of HPV vaccination among a diverse sample of adult women aged 27–45 years? (2) What are the characteristics of those who have or have not previously been vaccinated? and (3) What factors are associated with the intention to obtain the HPV vaccine among those who had never been vaccinated? Multivariable logistic regression analyses estimated adjusted odds ratios (AORs) and 95% confidence intervals (95% CIs).ResultsOnly 31.1% had at least one dose of the HPV vaccine. In multivariable analyses, those more likely to have been vaccinated were younger and were more likely to believe that the vaccine was effective. Of those unvaccinated or unsure, 54.8% indicated they were likely to get vaccinated in the future. Factors associated with future vaccine intention (compared to those not intending) included beliefs about vaccine testing, perceived likelihood of HPV infection, greater comfort in asking one’s provider for vaccination, and prior negative healthcare experiences.ConclusionsOur findings suggest that many women in this age group are interested in HPV vaccination. While the recommendation is for SCDM rather than routine vaccination for all women in this age group, efforts to promote informed decision-making among mid-adult women may include educating women about the rigorous vaccine testing and approval process, their risk factors for HPV infection, and encouraging them to engage in SCDM with their medical providers. Targeted efforts to reach women who have had negative experiences with healthcare may also be needed.

Prevalence and genotype distribution of human papillomavirus infection among 66000 women from 2014 to 2023 in the plateau region of Southwest China

BackgroundPersistent infection with high-risk human papillomavirus (HR-HPV) plays a key role in the onset of cervical cancer. This study was designed to examine the epidemiological trends and genotype distribution of HPV from 2014 to 2023 in the plateau region of Southwest China.MethodsThe findings could offer valuable insights for clinical screening of cervical cancer and the formulation of HPV vaccination policies. This retrospective study analyzed 66,000 women who received HPV-DNA testing at the First People’s Hospital of Qujing, Yunnan, China, between 2014 and 2023. The cohort consisted of 33,512 outpatients, 3,816 inpatients, and 28,672 individuals undergoing health examinations. Cervical cells were collected for DNA extraction, and PCR amplification along with Luminex xMAP technology were used to detect 27 HPV genotypes. The data analysis was conducted using GraphPad Prism and IBM SPSS Statistics 27 software.ResultsThe overall HPV infection rate at the First People’s Hospital of Qujing declined from 24.92% in 2014 to 16.29% in 2023, averaging 16.02%. Specific infection rates were 18.50% among outpatients, 12.97% among inpatients, and 13.53% for health examination attendees. The predominant high-risk HPV genotypes identified were HPV52 (2.61%), HPV16 (2.06%), HPV58 (1.81%), HPV53 (1.55%), and HPV39 (1.09%). Meanwhile, the most frequent low-risk HPV genotypes were HPV6 (1.30%), HPV61 (1.21%), and HPV11 (0.85%). In HPV-positive cases, the distribution of single, double, triple, and quadruple or more infections were 79.90%, 15.17%, 3.59%, and 1.33%, respectively. The proportions of pure LR-HPV, pure HR-HPV, and mixed infections were 22.16%, 67.82%, and 10.02%, respectively. Age-specific analysis revealed a bimodal distribution of HPV infection, with the infection rate rapidly decreasing from 44.02% in the ≤ 19 age group to 19.55% in the 20–29 age group and 13.84% in the 30–39 age group, followed by a gradual increase to 14.64% in the 40–49 age group, 16.65% in the 50–59 age group, and 22.98% in the ≥ 60 age group. The coverage rates of the three available vaccines are all below 50%. The results of this study indicated a declining trend in HPV prevalence in the plateau region of Southwest China over the period from 2014 to 2023, especially in the reduction of genotypes targeted by vaccines.ConclusionThere were significant variations in the genotypes prevalent among different age groups, years, and patient sources within the same region. The underwhelming vaccination rates emphasize the critical need for developing either a multivalent vaccine or a personalized vaccine that targets the HPV genotypes common in the Chinese population. Furthermore, vaccinating adolescents to curb HPV infection and ensuring regular cervical cancer screenings for postmenopausal women are crucial steps.

Application of change-point analysis to HPV infection and cervical cancer incidence in Xinjiang, China in 2011–2019

ObjectiveCervical cancer (CC), serving as a primary public health challenge, significantly threatens women’s health. However, in terms of change-points, there is still a lack of epidemiological studies on the incidence of HPV infection and CC in Xinjiang,China. This research aims to identify significant changes in the trends of HPV infection and CC prevalence in Xinjiang through change-point analysis (CPA) to provide scientific guidance to health authorities.MethodsHPV infection and CC time-series data (from January 2011 to December 2019) were collected and analyzed. Meanwhile, their change-points were detected with binary segmentation method and the PELT method. Furthermore, patients were assigned into three groups based on their different ages and subsequently subjected to an analysis employing a segmented regression model (SRM).ResultsIt was evident that for the monthly HPV time series, the binary segmentation method detected three change points in August 2015, February 2016, and September 2017 (with the most HPV cases). In contrast, the PELT method detected two change-points in September 2015 and April 2017 (with the most HPV cases). For the monthly CC time series, the binary segmentation method identified two change points in October 2012 and August 2019 (with the most CC cases), whereas the PELT method identified three change points in October 2012, August 2019 (with the most CC cases), and October 2019. The SRM demonstrated varying numbers of change points in distinct groups, with HPV infection and CC having the higher growth rate in the 30–49 and 40–59 age groups, respectively. Based on above results, this research was conductive to comprehending the epidemiology of HPV infection and CC in Xinjiang. In addition, it offered scientific guidance for future prevention and management measures for both HPV infection and CC.

Knowledge of HPV vaccination and associated HNC and treatment decision-making among minority populations

ObjectiveUnderstand vaccination knowledge and barriers to vaccination among minority adults. Study designCross-sectional survey. SettingOtolaryngology clinics at a safety net hospital and a tertiary academic center and a head and neck cancer screening event. MethodsSurvey was administered to consenting patients. Descriptive statistics and significance testing were used to characterize the data, with non-minority respondents as controls. Multivariate logistic regression was used to understand factors associated with vaccination. ResultsHPV vaccination among our 241 respondents (n = 41, 17.67 %) and their qualifying children (n = 52, 33.55 %) was low. Non-vaccinated minorities were significantly more likely to express interest in HPV vaccination (28.66 % vs 8.66 %, p = 0.016). Minority patients were significantly less knowledgeable about HPV causing cervical (88.64 % vs 72.45 %, p = 0.024) and head and neck (68.18 % vs 44.90 %, p = 0.005) cancer and were also less aware of HPV infection (95.45 % vs 81.12 %, p = 0.020) among non-women. Lack of knowledge about the HPV vaccine was the most cited reason why minority patients did not or were uninterested in vaccination for themselves or their children. In a multivariable logistic regression of factors associated with HPV vaccination, only increased age demonstrated a significant association with vaccination likelihood (OR = 0.91, 95 % CI = [0.88–0.95], p < 0.001). ConclusionReported HPV vaccination rates were low for both white and minority patients but did not significantly vary on univariate or multivariate analysis. However, minority respondents were significantly less knowledgeable about HPV and its manifestations; they most often cited inadequate knowledge as why did not receive or were uninterested in HPV vaccination. As such, HPV vaccination educational interventions may raise vaccination rates among minority populations.

Effects of Ellagic Acid on Vaginal Innate Immune Mediators and HPV16 Infection In Vitro.

Ellagic acid (EA) is a phenolic phytochemical found in many plants and their fruits. Vaginal epithelial cells are the first line of defense against pathogen invasion in the female reproductive tract and express antimicrobial peptides, including hBD2 and SLPI. This study investigated the in vitro effects of EA (1) on vaginal innate immunity using human vaginal epithelial cells, and (2) on HPV16 pseudovirus infection. Vaginal cells were cultured in the presence or absence of EA, and the expression of hBD2 and SLPI was determined at both transcriptional and translational levels. In addition, secretion of various cytokines and chemokines was measured. Cytotoxicity of EA was determined by CellTiter-blue and MTT assays. To investigate the ability of EA to inhibit HPV16 infection, EA was used to treat HEK-293FT cells in pre-attachment and adsorption steps. We found significant increases in both hBD2 mRNA (mean 2.9-fold at 12.5 µM EA, p < 0.001) and protein (mean 7.1-fold at 12.5 µM EA, p = 0.002) in response to EA. SLPI mRNA also increased significantly (mean 1.4-fold at 25 µM EA, p = 0.01), but SLPI protein did not. Secretion of IL-2 but not of other cytokines/chemokines was induced by EA in a dose-dependent manner. EA was not cytotoxic. At the pre-attachment step, EA at CC20 and CC50 showed a slight trend towards inhibiting HPV16 pseudovirus, but this was not significant. In summary, vaginal epithelial cells can respond to EA by producing innate immune factors, and at tested concentrations, EA is not cytotoxic. Thus, plant-derived EA could be useful as an immunomodulatory agent to improve vaginal health.

The Relationship Between Metal Exposure and HPV Infection: Evidence from Explainable Machine Learning Methods.

HPV is a ubiquitous pathogen implicated in cervical and other cancers. Although vaccines are available, they do not encompass all subtypes. Meanwhile, metal exposure may elevate the risk of HPV infection and amplify its carcinogenic potential, but studies to further elucidate this relationship are insufficient.This study entailed a cross-sectional analysis utilizing data from the National Health and Nutrition Examination Survey (NHANES) 2007-2016. The study sample comprised 2765 women. Multivariate logistic regression was employed to examine the association between single metal exposure and HPV infection, weighted quantile sum (WQS) regression was utilized for assessing the mixed metal exposure effect, and the XGBoost + SHapley Additive exPlanations (SHAP) to evaluate the contribution of metal exposure in HPV infection.Multivariate logistic regression analysis indicated that elevated Co concentration was inversely associated with HPV infection (OR 0.891; 95% CI 0.814-0.975), while elevated Pb concentration correlated with an increased HPV infection (OR 1.176; 95% CI 1.074-1.287). Regression analysis of the WQS for mixed metal exposure suggested that the WQS index was potentially linked to an increased likelihood of HPV infection in the positive direction (OR 1.249; 95% CI 1.052-1.482), with no significant association observed in the negative direction (OR 0.852; 95% CI 0.713-1.017). SHAP analysis prioritized the importance of characteristics: number of sexual partners, marital status, poverty-to-income ratio (PIR), Co, Pb, and alcohol consumption.Exposure to Pb was associated with an increase in the incidence of HPV infection, whereas Co exposure demonstrated an inverse relationship. The composite exposure to multiple metals showed a positive association with the prevalence of HPV infection. These findings indicate that exposure to metals could potentially escalate the prevalence of HPV infection.

Male Tract Microbiota and Male Infertility.

In recent years, several studies have analyzed the composition of the male genital tract microbiota and its changes in infertility or in different situations associated with infertility. The aim of this narrative review is to obtain more insight on this topic; in particular, to describe actual evidence about changes in the semen microbiota in patients with infertility, male tract infections, or HPV infections. In semen, an increase in semen Prevotella spp. is associated with oligozoospermia and with obesity-associated asthenozoospermia; an increase in Pseudomonas is more frequently associated with asthenozoospermia and oligozoospermia; a reduction in Lactobacilli spp. (namely in Lactobacillus crispatus) may represent a marker of low semen quality. However, an increase in Lactobacillus iners is considered a risk factor for a reduced sperm concentration. In patients with prostatitis, there is a reduction in Lactobacillus spp. and an increase in Streptococcus spp., opening important perspectives about the role of probiotic treatments in these patients. Finally, an increase in Fusobacteria spp. was observed in patients with an HPV infection. In the conclusion, we underline the interactions between the seminal and vaginal microbiota, so that further studies should focus on the "couple genital microbiota".

Human papillomavirus vaccine delivery practices among pediatricians and pediatric trainees in a tertiary hospital in Singapore

AbstractHuman Papillomavirus (HPV) is the most common sexually transmitted infection and is associated with cervical, anogenital, and oropharyngeal cancers. It is crucial to improve vaccination uptake in both genders as primary prevention for these conditions. Pediatricians play an active role in advocating for HPV vaccination and our study aims to assess the level of knowledge, attitudes, barriers, and practices among pediatric trainees and general pediatricians regarding HPV infection and vaccination. A survey‐questionnaire was administered to our target groups. It comprised 14 questions regarding demographics of the healthcare provider, knowledge of HPV infection and vaccination, practices and barriers of recommending HPV vaccination, and effective strategies for improving HPV vaccine uptake. Among survey respondents, majority did not recommend for HPV vaccination (66.7%) or receive any enquiry about it (80.6%) within the preceding 12 months. The most common perceived barrier was inadequate knowledge, which was consistent with the misconceptions regarding HPV infection and vaccination that were identified in this survey. Strategies which physicians felt would be most effective in increasing vaccine uptake include educating and providing resources for both physicians and caregivers as well as making the vaccine free. Our study revealed a low advocacy rate for HPV vaccination. Physicians need to be equipped with the knowledge, skills, and resources to better counsel caregivers as well as focus our efforts on vaccinating male patients in order to increase vaccine uptake in both genders.

Telomere Length, Telomerase Activity, and Vaginal Microbiome in Patients with HPV-Related Precancerous Lesions.

Persistent high-risk human papillomaviruses (HR HPVs) infection leads to the development of squamous intraepithelial lesions in cervical cells that may lead to cancer. The telomere length, telomerase activity, and species composition of the vaginal microbiome may influence the dynamic of changes and the process of carcinogenesis. In the present study, we analyze relative telomere length (RTL), relative hTERT expression (gene for the telomerase component-reverse transcriptase) in cervical smear cells and vaginal microbiomes. Total RNA and DNA were isolated from tissue samples of 109 patients from the following groups: control, carrier, low-grade or high-grade squamous intraepithelial lesion (L SIL and H SIL, respectively), and cancer. The quantitative PCR method was used to measure telomere length and telomerase expression. Vaginal microbiome bacteria were divided into community state types using morphotype criteria. Significant differences between histopathology groups were confirmed for both relative telomere length and relative hTERT expression (p < 0.001 and p = 0.001, respectively). A significant difference in RTL was identified between carriers and H SIL (p adj < 0.001) groups, as well as between carriers and L SIL groups (p adj = 0.048). In both cases, RTL was lower among carriers. The highest relative hTERT expression level was recorded in the H SIL group, and the highest relative hTERT expression level was recorded between carriers and the H SIL group (p adj < 0.001). A correlation between genotype and biocenosis was identified for genotype 16+A (p < 0.001). The results suggest that identification of HPV infection, telomere length assessment, and hTERT expression measurement together may be more predictive than each of these analyses performed separately.

Factors associated with human papillomavirus infections among women living with HIV in public health facilities in Western Oromia, Ethiopia

BackgroundHuman Papillomavirus infection (HPV) is among the most common sexually transmitted infections with the highest incidence and prevalence worldwide. HPV has been established as the main cause of cervical cancer and remains a public health problem globally. In Western Oromia, Ethiopia cervical screening remains a major issue because of limited resources, and shortage of HPV testing technology. As a result, the prevalence of HPV and associated factors remain unknown among HIV-positive women. This study aimed to assess the prevalence of HPV and associated factors among women living with HIV attending Antiretroviral Therapy (ART) services in public health facilities of East Wollega and West Showa Zones, Ethiopia, 2022.MethodUsing a cross-sectional study design, a total of 415 women ≥ 18 years old were enrolled using systematic random sampling from five public health facilities. Cervical specimens were collected by a trained nurse from April 01 2022, to May 30, 2022, and tested at Nekemte Public Health Research and Referral Molecular Biology, a certified/accredited laboratory for HPV-DNA Polymerase Chain Reaction by expertise using Abbott m2000rt-PCR assays. Finally, Epi data version 4.6 was used for data entry and SPSS version 24.0 were used for data cleaning and analysis, and frequencies and prevalence of HPV were computed. Variables were identified using the multivariable model and statistically significant associations of variables were determined based on the adjusted odds ratio (AOR) with its 95% CI and P-value < 0.05 to determine the strength of association.ResultThe prevalence of HPV was 30.4% [95% CI: 26.0, 34.9]. Of HPV-infected women, 11.9% were positive for HPV-16, 9.5% for HPV-18, and 65.9% were positive for other hr-HPV . The odds of HPV infection among women aged beyond 48 years are 2.85 times the odds of HPV among people who were aged 18–27(AOR = 2.85, 95% CI: 1.16, 5.58). The odds of HPV infection among women who had three or more sexual partners is 4.12 times the odds of HPV infection among women with a single sexual partner(AOR = 4.12, 95% CI: 2.34–8.62). The odds of HPV infection among women who didn’t use condom during sexual intercourse are 4.73 times the odds of HPV among women who used condom during sexual intercourse. (AOR = 4.73, 95% CI: 1.98–9.33). The odds of HPV infection among women who had history of is 4.52 times the odds of HPV infection among women with no history of abortion. [AOR = 4.52, 95% CI: 2.04, 6.89] The odds of HPV infection among women with history of Sexually Transmitted Infection (STI) 3.62 times the odds of HPV among women with no history of STI (AOR = 3.62, 95%CI: 1.75, 5.83). The odd of HPV among women with abnormal vaginal discharge is 3.31 times the odds of the disease among women with normal vaginal discharge [AOR = 3.31, 95% CI: 2.87,7.35).Conclusion and recommendationThe prevalence of HPV infection among HIV-infected women was high in the study area. Given the above-associated factors, we recommend that the stakeholders integrate HPV prevention strategies into HIV /AIDS services. Furthermore, the study has provided essential information about the HIV link with hr-HPV infections, which may explain the high prevalence among HIV-infected women. This can contribute to policy development and planning of prevention strategies incorporating HPV infection prevention especially among youth and HIV-infected people.

Effectiveness of vaginal probiotics Lactobacillus crispatus chen-01 in women with high-risk HPV infection: a prospective controlled pilot study.

Female genital tract infection with high-risk human papilloma virus (HR-HPV) has the risk of developing into cervical cancer, and there is still a lack of effective therapeutic strategies. Probiotic intervention is considered as a potential intervention for HR-HPV, while exploration into living probiotic preparations for specific diseases remains limited and insufficient. This prospective controlled pilot study was conducted to observe the effect of intravaginal transplantation of a vaginal isolated natural probiotic strain, Lactobacillus crispatus chen-01, on the clearance of high-risk HPV infection. 100 women with high-risk HPV infection were enrolled and randomly divided into placebo group and probiotic treatment group, which received intravaginal transplantation of L. crispatus chen-01. Cervical exfoliated cells were collected 6 months later for detecting DNA load, typing of HPV, and cytological analysis. Our results showed that vaginal transplantation with L. crispatus chen-01 significantly reduced viral load of HPV, ameliorated HPV clearance rate, and improved vaginal inflammation state without causing obvious adverse reactions. Analysis of 16S rRNA sequencing revealed that L. crispatus chen-01 could effectively reconstitute the vaginal microbiota in women with high-risk HPV, which might be one of the underlying mechanisms of the beneficial effect of L. crispatus chen-01 transplantation. Our results suggested that vaginal transplantation of L. crispatus chen-01 might be a promising treatment for patients with high-risk HPV infection.

Computational insights into CRISP3 downregulation in cervical cancer and its cervical lineages pattern.

Cysteine-rich secretory protein 3 (CRISP3) emerges as a potential biomarker in the study of many cancers, including cervical cancer (CC). This study aimed to analyze the expression pattern of CRISP3 in CC patients and CC cell lineages, following treatment with the epigenetic drugs: trichostatin A (TSA) and 5-aza-2'-deoxycytidine (5-aza). The differentially expressed genes identified in GSE63514 were used to construct a protein-protein interaction network. CRISP3 was selected for subsequent analyses. We utilized data from the TCGA and GENT2 projects to evaluate the expression profile and clinical behavior of CRISP3. Additionally, we conducted cell culture experiments to analyze the expression profile of CRISP3 in cells. Low levels of CRISP3 were observed in squamous cell carcinoma (SCC) and human papillomavirus (HPV)16+, along with being associated with worse overall survival (OS). MIR-1229-3p was analyzed, and its high expression was associated with worse prognostic outcomes. In CC-derived cell lines, we observed low levels of CRISP3 in SiHa, followed by SW756, C33A, HeLa, and higher levels in CaSki. All cells were treated with TSA, 5-aza, or both. In all cell lines, treatment with TSA resulted in increased transcription of CRISP3. We identified a significant downregulation of CRISP3 in CC, particularly in cases with HPV16 infection and SCC, which was associated with poorer OS. Preliminary findings suggest that epigenetic treatments with TSA and 5-aza may modulate CRISP3 expression, warranting further research to elucidate its regulatory mechanisms and potential as a prognostic biomarker.

Traditional Chinese Medicine Erhuang Suppository for Treatment of Persistent High-risk Human Papillomavirus Infection and Its Impact on Transcriptome of Uterine Cervix.

High-risk human papillomavirus (HR-HPV) infection is the chief cause of cervical intraepithelial neoplasia (CIN) and cervical carcinoma. The Erhuang suppository (EHS) is a traditional Chinese medicine (TCM) prepared from realgar (As2S2), Coptidis rhizoma, alumen, and borneolum syntheticum and has been used for antiviral and antitumor purposes. However, whether EHS can efficiently alleviate HR-HPV infection remains unclear. This study was conducted to evaluate the efficacy of EHS for the treatment of persistent HR-HPV infection in the uterine cervix. In this study, we evaluated the therapeutic efficacy of EHS in a randomized controlled clinical trial with a 3-month follow-up. Totally, 70 patients with persistent HR-HPV infection were randomly assigned to receive intravaginal administration of EHS or placebo. HPV DNA, ThinPrep cytologic test (TCT), colposcopy, and safety evaluation were carried out after treatment. Microarray analysis was performed to compare transcriptome profiles before and after EHS treatment. A K14-HPV16 mouse model was generated to confirm the efficiency of EHS. After 3 months, 74.3% (26/35) of the patients in the treatment group were HPV negative, compared to 6.9% (2/29) in the placebo group. High-throughput microarrays revealed distinct transcriptome profiles after treatment. The differentially expressed genes were significantly enriched in complement activation, immune response, and apoptotic processes. The K14-HPV16 mouse model also validated the remarkable efficacy of EHS. This study demonstrated that EHS is effective against HR-HPV infection and cervical lesions. Additionally, no obvious systemic toxicity was observed in patients during the trial. The superior efficacy and safety of EHS demonstrated its considerable value as a potential cost-effective drug for the treatment of HPV infection and HPV-related cervical diseases.

Comment on, “Characterization of oral microbiota in HPV and non-HPV head and neck squamous cell carcinoma and its association with patient outcomes”

The article “Characterization of oral microbiota in HPV and non-HPV head and neck squamous cell carcinoma and its association with patient outcomes” by Chan et al. investigates the relationship between oral microbiota, HPV infection, and patient outcomes in head and neck squamous cell carcinoma (HNSCC). This comprehensive study, involving 166 Chinese adults, utilized advanced sequencing techniques to profile bacterial and HPV regions in paired tumor and control tissues. The findings highlight the complex interplay between microbiota dysbiosis, HPV infection, and HNSCC progression. Despite the robustness of the study, limitations include potential biases in DNA extraction and PCR amplification, and unaccounted environmental factors. Recommendations for future research include increasing sequencing depth, comparing DNA extraction methods, using multiple bioinformatics pipelines, and controlling for environmental variables. Longitudinal studies and microbiota-targeted interventions are suggested to further elucidate the role of oral microbiota in HNSCC and improve patient outcomes.

Association between human papillomavirus and preterm delivery: A systematic review and meta-analysis.

The lifetime prevalence of human papillomavirus infection (HPV) is estimated to be around 80% and it is the most common sexually transmitted infection. Despite being well known for its oncologic relevance, it has been associated with adverse pregnancy outcomes, though available evidence is contradicting. Previous meta-analyses involved articles which based HPV infection on Pap smear results, leading to a significant source of bias. Therefore, we aimed to assess the burden of genetically proven HPV infection on adverse pregnancy outcomes. In our meta-analysis, pregnant women tested for HPV DNA were only considered eligible. We conducted a systematic search in three major databases (PubMed, Embase, and CENTRAL) on September 22, 2023. Cohort, cross-sectional, and case-control studies were eligible for the analysis. The exposed group consisted of HPV-infected patients. We assessed the odds ratios (OR) with a confidence interval (CI) of 95%. In order to reduce the heterogeneity, we performed subgroup analyses based on different strains (high risk HPV, HPV 16/18, study design). The study was prospectively registered on PROSPERO (CRD42022370228). Our study involved 14 articles with 7008 women. A significant association was found between preterm delivery and HPV infection (OR: 1.94, CI: 1.31-2.87). No significant association was found when separately examining high-risk HPV-infected women (OR: 1.94, CI: 0.82-4.59), and HPV 16 or 18-infected women (OR: 2.08, CI: 0.50-8.63) in terms of preterm delivery. No significant association was found between spontaneous abortion and HPV infection (OR: 1.02, CI: 0.16-6.31). Our analysis indicates an association between HPV infection and preterm delivery. It is imperative that future studies consider confounding variables more comprehensively. Additionally, the global implementation of HPV vaccination programs holds significance not only in oncology but also in obstetrics.

Vaginal Intraepithelial Neoplasia (VaIN) after Hysterectomy Is Strongly Associated with Persistent HR-HPV Infection.

This retrospective study was conducted on 170 women who underwent a laparoscopic hysterectomy due to high-grade cervical intraepithelial neoplasia (CIN3) or benign gynecological disease. The follow-up strategy included performing a cotest and colposcopy with biopsy if necessary. The median time between primary treatment and a diagnosis of high-grade VaIN was 18 months. High-grade or severe VaIN was found in eight patients after hysterectomy (4.7%). All cases of high-grade VaIN occurred in women with persistent HPV infection. The most frequent genotype was 16. Women hysterectomized due to CIN3 showed an eight-fold greater risk than women hysterectomized due to benign disease of developing high-grade VaIN. The risk of VaIN is low in women hysterectomized due to benign disease. The risk of developing VaIN is greater in women with viral persistence. All these elements suggest that it is a history of HPV-related disease of the lower genital tract and viral persistence, rather than hysterectomy itself, that should be considered risk factors for the development of high-grade VaIN. After hysterectomy, patients with a history of CIN should undergo annual screening with vaginal dome cytology and HPV testing.

Prevalence of human papillomavirus genotypes in women of different ethnicity from rural northwestern Ecuador

BackgroundIn Ecuador, cervical cancer is the third most common cancer among women and the second most common cause of cancer-related death in women. Although HPV represents a serious public health problem worldwide, the information about its prevalence and genotypes in remote communities of Ecuador is limited. The aim of this study was to determine the distribution of HPV genotypes among ethnic minority women from two remote communities of the northwestern region of Ecuador: Afro-Ecuadorians and Chachis (Amerindian group).MethodsWe included 291 women who responded to a short survey and were screened for HPV by the amplification of the L1 gene and a nested multiplex PCR to detect 14 high risk (HR) genotypes. A survey collected information on ethnicity, age, community access, and sexual and gynecological history. We identified risk factors associated with HPV infection and co-infection using multivariate logistic regression to calculate odds ratio (OR) and Wald 95% confidence intervals (CI).ResultsOverall, HPV prevalence in the study cohort was 56%, and the five most common HR-HPV genotypes were HPV-58, -16, -68, -39, and -43; however, the distribution of HPV genotypes varied according to ethnicity. We identified lineage A (European variant) for HPV-16 and sublineage A2 for HPV-58 in both ethnic groups. Adjusting for ethnicity, age, community access, and number of sexual partners, we found that Afro-Ecuadorian women were less likely to have an HPV infection than Chachi women (OR: 0.49, 95% CI: 0.25, 0.96), and that participants in communities only accessible by river had 64% less chances of an HPV infection when compared to women in communities accessible by road (OR: 0.36, 95% CI: 0.19, 0.71), and women with 2 to 3 sexual partners had 2.47 times the odds of HPV infection than participants with 0–1 partners (OR: 2.47, 95% CI: 1.32, 4.6). Similar associations were observed with prevalence of co-infection.ConclusionsThis study provides baseline knowledge regarding the prevalence and distribution of HPV genotypes in ethnic groups of the northwestern coastal Ecuador and essential information for the implementation of appropriate HPV testing and vaccination program to prevent cervical cancer.

Time to take HPV infection in colorectal cancer patients more seriously.

The association between viral infections and colorectal cancer (CRC) remains an enigma in cancer research. Certain types of Human Papillomaviruses (hr-HPVs), known for their oncogenic properties, have been observed in particular CRC biopsies, further adding to the enigma surrounding this association. This cross-sectional study was conducted on 40 confirmed cases of CRC adenocarcinoma. The presence and genotyping of HPV DNA in colorectal fresh tissue and urine samples was assessed using an HPV DNA hybridization kit. A subset of serum samples from both CRC cases and healthy volunteers was randomly chosen and subjected to western blot to investigate the presence of HPV16 E6/E7 oncoproteins carried by exosomes. It was observed that 26/40 HPV-positive CRC patients demonstrated 7 times more chance to develop colorectal cancer when compared to those 8/40 normal tissue (odds ratio [OR] = 7.4; confidence interval [CI] 95% = 0.483156-0.793718; p < 0.001). Of 26 HPV-positive CRC patients, 14 urine samples were also showed HPV DNA positivity (p = 0.013). High-risk HPV16 was the most prevalent genotype detected in both 24/40 tumor and 12/40 urine samples (p < 0.001). The tumor sample of a male was HPV45, while another male's urine sample was HPV31. A female CRC patient had HPV83 in tumor and HPV56 in urine. Here, was the first detection of HPV83 in a CRC patient. Notably among 20 randomly selected serum exosome samples, one serum sample concurrently tested positive for both HPV16 E6 and E7 oncoproteins, and one sample tested positive for HPV16 E7 oncoprotein. High risk HPV DNA detection in CRC urine samples supports non-invasive screening tools. Detection of HPV16 E6 and E7 oncoproteins in exosomes from serum samples shows potential for non-invasive diagnostics. HPV's potential role in CRC development is also underscored. HPV vaccination should be implemented in low- and middle-income countries to prevent cancer.