Persistent Human Papillomavirus Research Articles

Microhomology-mediated repair machinery and its relationship with HPV-mediated oncogenesis.

Human Papillomaviruses (HPV) are a diverse family of non-enveloped dsDNA viruses that infect the skin and mucosal epithelia. Persistent HPV infections can lead to cancer frequently involving integration of the virus into the host genome, leading to sustained oncogene expression and loss of capsid and genome maintenance proteins. Microhomology-mediated double-strand break repair, a DNA double-stranded breaks repair pathway present in many organisms, was initially thought to be a backup but it's now seen as vital, especially in homologous recombination-deficient contexts. Increasing evidence has identified microhomology (MH) near HPV integration junctions, suggesting MH-mediated repair pathways drive integration. In this comprehensive review, we present a detailed summary of both the mechanisms underlying MH-mediated repair and the evidence for its involvement in HPV integration in cancer. Lastly, we highlight the involvement of these processes in the integration of other DNA viruses and the broader implications on virus lifecycles and host innate immune response.

Prevalence of high-risk human papillomavirus infection among women with diabetes mellitus in Accra, Ghana

BackgroundThere is increasing evidence of a higher risk and poorer prognosis of cervical cancer among women with diabetes mellitus (DM) compared to the general population. These are mediated by higher susceptibility to persistent high-risk human papillomavirus (hr-HPV) infection due to dysfunctional clearance in an immunocompromised state. We aimed to determine the prevalence of hr-HPV infection and cervical lesions in a cohort of women with DM in Ghana. We further disaggregated the prevalence according to DM type and explored factors associated with hr-HPV infection.MethodsThis retrospective descriptive cross-sectional study assessed 198 women with DM who underwent cervical screening via concurrent hr-HPV DNA testing and visual inspection with acetic acid in an outpatient department of the National Diabetes Management and Research Centre in Korle-Bu Teaching Hospital, Accra from March to May 2022. Univariate and multivariable binary logistic regression were used to explore factors associated with hr-HPV positivity.ResultsAmong 198 women with DM (mean age, 60.2 ± 12.1 years), the overall hr-HPV prevalence rate was 21.7% (95% CI, 16.1–28.1), disaggregated as 1.5% (95% CI, 0.3–4.4) each for HPV16 and HPV18 and 20.7% (95% CI, 15.3–27.0) for other HPV genotype(s). Respective hr-HPV prevalence rates were 37.5% (95% CI, 15.2–64.6) for type 1 DM, 19.8% (95% CI, 13.9–26.7) for type 2 DM, and 25.0% (95% CI, 8.7–49.1) for unspecified/other DM types. Past use of the combined contraceptive pill independently increased the risk of hr-HPV infection by approximately three times (adjusted odds ratio [aOR] = 2.98; 95% CI, 1.03 − 8.64; p-value = 0.045), whereas each unit increase in FBG level increased the odds of hr-HPV infection by about 15% (aOR = 1.15; 95% CI, 1.02 − 1.30; p-value = 0.021).ConclusionOur study points to a high prevalence of hr-HPV among women with DM and highlights a need for glycemic control among them as this could contribute to lowering their odds of hr-HPV infection. The low overall rates of HPV vaccination and prior screening also indicate a need to build capacity and expand the scope of education and services offered to women with DM as regards cervical precancer screening.

Serum Proteomic Signatures in Cervical Cancer: Current Status and Future Directions.

In 2020, the World Health Organization (WHO) reported 604,000 new diagnoses of cervical cancer (CC) worldwide, and over 300,000 CC-related fatalities. The vast majority of CC cases are caused by persistent human papillomavirus (HPV) infections. HPV-related CC incidence and mortality rates have declined worldwide because of increased HPV vaccination and CC screening with the Papanicolaou test (PAP test). Despite these significant improvements, developing countries face difficulty implementing these programs, while developed nations are challenged with identifying HPV-independent cases. Molecular and proteomic information obtained from blood or tumor samples have a strong potential to provide information on malignancy progression and response to therapy in CC. There is a large amount of published biomarker data related to CC available but the extensive validation required by the FDA approval for clinical use is lacking. The ability of researchers to use the big data obtained from clinical studies and to draw meaningful relationships from these data are two obstacles that must be overcome for implementation into clinical practice. We report on identified multimarker panels of serum proteomic studies in CC for the past 5 years, the potential for modern computational biology efforts, and the utilization of nationwide biobanks to bridge the gap between multivariate protein signature development and the prediction of clinically relevant CC patient outcomes.

The role of NF-κB in carcinogenesis of cervical cancer: opportunities and challenges.

The nuclear factor-κB (NF-κB) family, consisting of several transcription factors, has been implicated in the regulation of cell proliferation and invasion, as well as inflammatory reactions and tumor development. Cervical cancer (CC) results from long-term interactions of multiple factors, among which persistent high-risk human papillomavirus (hrHPV) infection is necessary. During different stages from early to late after HPV infection, the activity of NF-κB varies and plays various roles in carcinogenesis and progress of CC. As the center of the cell signaling transduction network, NF-κB can be activated through classical and non-classical pathways, and regulate the expression of downstream target genes involved in regulating the tumor microenvironment and acquiring hallmark traits of CC cells. Targeting NF-κB may help treat CC and overcome the resistance to radiation and chemotherapy. Even though NF-κB inhibitors have not been applied in clinical treatment as yet, due to limitations such as dose-restrictive toxicity and poor tumor-specificity, it is still considered to have significant therapeutic potential and application prospects. In this review, we focus on the role of NF-κB in the process of CC occurrence and hallmark capabilities acquisition. Finally, we summarize relevant NF-κB-targeted treatments, providing ideas for the prevention and treatment of CC.

Human malignancies associated with persistent HPV infection.

Human papillomavirus (HPV)-associated malignancies account for ~5% of human cancers worldwide. Thirteen, or more, HPV types are oncogenic, but infection with these viruses is common and usually cleared within 2 years. Only infections that become persistent are associated with the development of cancer, often occurring several decades later. These cancers mostly arise in 6 different anatomical regions: 5 are anogenital (anus, cervix, penis, vagina, and vulva) and the sixth is the oropharynx. Oncogenic HPVs promote cellular proliferation and genomic instability, but the anatomical niche of the target tissue also plays an important role in the development of cancer. Cells that reside in transitional regions between different types of epithelia, such as in the anus, cervix, and oropharynx, are particularly vulnerable to oncogenesis.

Incidence, Clearance and Persistence of Penile High-Risk Human Papillomavirus among Rwandan Men who have Sex with Men

Abstract Background Little is known about penile high-risk HPV among MSM in low-and-middle income countries. We aimed to determine the incidence, clearance and persistence of penile hrHPV among Rwandan MSM. Methods We enrolled 350 MSM (345 with valid HPV results), aged ≥18 years, at each visit (6-12 months apart), we collected penile PreservCyt specimens and blood for HPV and HIV testing, socio-demographic and behavioral variables. HPV testing was performed using the Ampfire assay. Penile hrHPV incidence and clearance/1,000 person-months of follow-up (PMF), prevalent- and incident-persistence were computed and compared by HIV status. Results The mean age was 27.7 ± 6.7 years and 19.4% were living with HIV. Penile hrHPV incidence was 34.8 (95% CI: 29.1, 41.8)/1,000 PMF. HPV16 (11.7, CI 9.26, 14.9) and HPV59 (6.1, CI 4.52, 8.39) had the highest incidence rates. Prevalent- and incident-persistence were 47.5% and 46.6%, respectively. HPV66 (33.3%), HPV52 (30.8%) and HPV16 (29.2%) had the highest prevalent-persistence and HPV33 (53.8%), HPV31 (46.7%) and HPV16 (42.6%) the highest incident-persistence. No differences were found by HIV status except for HPV45 (higher in MSM with HIV). Conclusion We found high incidence and prevalent/incident-persistence of penile hrHPV among Rwandan MSM. This highlights the importance of preventive strategies for HPV-associated anogenital cancers.

The importance of combined HPV and CINtec® PLUS genotyping testing for p16 in women with cervical squamous cell carcinoma.

Immunohistochemistry (IHC) for p16INK4A (p16) is a reliable surrogate test for the presence of a high-risk, potentially transformative human papillomavirus (HPV) infection in precursor and malignant lesions of the cervix. The purpose of this study was to evaluate changes in cervical cells caused by persistent HPV infection, by IHC (p16 protein) by comparison with HPV genotyping. The study included female patients aged between 26 and 57 years who presented to a public hospital, with complaints related to the genital area, namely vaginal bleeding and dyspareunia. After selecting the patients, samples were subjected to cytological testing and IHC for p16 and for the determination of HPV types. The relationship between HPV status and p16 status was statistically significant (p=0.0001), of the 41 patients, 53.7% were HPV positive, respectively 56.1% were p16 positive, the agreement relationship between the two indicators was very high (weighted kappa: 0.951). The clinical performance of CINtec® PLUS triage for p16 shows a high positive predictive value (PPV) and a high negative predictive value (NPV) of 95.7% and 100%, respectively, as regards HPV. The p16 marker (CINtec® PLUS) can be used as a prognostic biomarker and provides clinical usefulness through increased sensitivity (Se) and specificity (Sp) in the triage of women at risk of developing precancerous lesions, compared to cytology that is based on morphology, but has a rather low Se and high Sp, while HPV testing is very sensitive but slightly more specific.

Prevention and treatment of HPV-related cancer through a mRNA vaccine expressing APC-targeting antigen.

Persistent human papillomavirus (HPV) infection is associated with multiple malignancies. Developing therapeutic vaccines to eliminate HPV-infected and malignant cells holds significant value. In this study, we introduced a lipid nanoparticle encapsulated mRNA vaccine expressing tHA-mE7-mE6. Mutations were introduced into E6 and E7 of HPV to eliminate their tumourigenicity. A truncated influenza haemagglutinin protein (tHA), which binds to the CD209 receptor on the surface of dendritic cells (DCs), was fused with mE7-mE6 in order to allow efficient uptake of antigen by antigen presenting cells. The tHA-mE7-mE6 (mRNA) showed higher therapeutic efficacy than mE7-mE6 (mRNA) in an E6 and E7+ tumour model. The treatment resulted in complete tumour regression and prevented tumour formation. Strong CD8+ T-cell immune response was induced, contributing to preventing and curing of E6 and E7+ tumour. Antigen-specific CD8+ T were found in spleens, peripheral blood and in tumours. In addition, the tumour infiltration of DC and NK cells were increased post therapy. In conclusion, this study described a therapeutic mRNA vaccine inducing strong anti-tumour immunity in peripheral and in tumour microenvironment, holding promising potential to treat HPV-induced cancer and to prevent cancer recurrence.

Novel biomarkers of inflammation-associated immunity in cervical cancer.

Cervical cancer (CC) is a highly malignant gynecological cancer with a direct causal link to inflammation, primarily resulting from persistent high-risk human papillomavirus (HPV) infection. Given the challenges in early detection and mid to late-stage treatment, our research aims to identify inflammation-associated immune biomarkers in CC. Using a bioinformatics approach combined with experimental validation, we integrated two CC datasets (GSE39001 and GSE63514) in the Gene Expression Omnibus (GEO) to eliminate batch effects. Immune-related inflammation differentially expressed genes (DGEs) were obtained by R language identification. This analysis identified 37 inflammation-related DEGs. Subsequently, we discussed the different levels of immune infiltration between CC cases and controls. Weighted gene co-expression network analysis (WGCNA) identified seven immune infiltration-related modules in CC. We identified 15 immune DEGs associated with inflammation at the intersection of these findings. In addition, we constructed a protein interaction network using the String database and screened five hub genes using "CytoHubba": CXC chemokine ligand 8 (CXCL8), CXC chemokine ligand 10 (CXCL10), CX3C chemokine receptor 1 (CX3CR1), Fc gamma receptors 3B (FCGR3B), and SELL. The expression of these five genes in CC was determined by PCR experiments. In addition, we assessed their diagnostic value and further analyzed the association of immune cells with them. Five inflammation- and immune-related genes were identified, aiming to provide new directions for early diagnosis and mid to late-stage treatment of CC from multiple perspectives.

Knowledge and Practices Regarding Human Papillomavirus and Cervical Cancer Screening Among Women in Low-Income Areas of China: A Cross-Sectional Study.

Persistent human papillomavirus (HPV) infection is the primary cause of cervical cancer. However, this can be prevented through vaccination and screening. This study aimed to clarify the relationship between behavior, knowledge, and attitude toward cervical cancer and regular screening and HPV infection among women in Lueyang County. Women who underwent cervical cancer screening at the outpatient department of a maternal and child health center between September and December 2021 were invited to participate. In total, 2,303women completed the questionnaire. Women who underwent regular or irregular screening were 1:1 matched for age. Differences in knowledge of HPV and attitudes toward HPV vaccination among different populations were assessed. Logistic regression analysis was performed to identify the factors influencing HPV infection. In total, 417 pairs of women who underwent regular and irregular screening were successfully matched. Multivariate logistic regression results indicated that age is a risk factor for HPV infection (OR=1.05695%CI: [1.0311.082]), while regular screening acts as a protective factor against HPV infection (OR=0.17495%CI: [0.1170.259]). Additionally, regular screening was associated with a higher level of knowledge about HPV among women compared to those who did not undergo regular screening (p<0.001). Women in Lueyang County have low levels of knowledge regarding HPV and cervical cancer. Regular screening is a protective factor against HPV infection. The regular screening group demonstrates a higher level of HPV knowledge compared with the irregular screening group. These findings highlight the importance of regular screening and the need to strengthen public health education.

Association between human papillomaviruses, metabolic syndrome, and all-cause death; analysis of the U.S. NHANES 2003-2004 to 2015-2016.

Human papillomavirus (HPV) is the most common sexually transmitted infection, attributed to 4.5% of all cancers worldwide. Co-infection with the metabolic syndrome (MetS), a common cluster of cardiometabolic risk factors, has been shown to increase the persistence of HPV. The purpose of this study was to estimate the association between HPV and MetS on mortality risk. Data for the current study was drawn from seven consecutive cycles (2003-2004 to 2015-2016) of the U.S. NHANES. The final analytic sample consisted of 5,101 individuals aged 18-65y with HPV and MetS information with follow-up to Dec. 31st, 2019. Baseline HPV status was assessed by either vaginal swab, penile swab or oral rinse and used to classify participants as: no HPV (n = 1,619), low (n = 1,138), probable (n = 672), and high-risk (n = 1,672; 22% type 16, and 10% type 18) HPV using IARC criteria. MetS was assessed by the Harmonized criteria. The average follow-up was 9.4 y with 240 all-cause deaths (no HPV: n = 46 deaths; low-risk: n = 60 deaths; probable: n = 37 deaths, and; high-risk: n = 97 deaths). HPV status alone revealed no associations with mortality in fully adjusted models. Cross-classification into discrete MetS/HPV strata yielded an increased risk of mortality in females with high-risk HPV/MetS relative to the no MetS/no HPV group. In this study, low, probable, and high-risk HPV and MetS were differentially related to mortality risk in men and women. Further work is necessary to separate the temporal, age, vaccination, and sex effects of HPV diagnosis in these relationships using prospective studies with detailed histories of HPV infection and persistence.

Human Leucocyte Antigen Class II Risk and Protective Alleles in Women with Cervical Intraepithelial Neoplasia

Background: Persistent human papillomavirus (HPV) infection is a necessary cause for development of cervical precancerous lesions and cervical cancer, however, only a small percentage of women progress to cervical cancer. The local immune response, determined, among other factors, by Human Leucocyte Antigen (HLA) genes, is thought to be significant. Still the results of genome studies are inconsistent and differ between ethnical populations. The aim of the study was to assess an association between HLA-DQA1*; DQB1*; DRB1* allele’s genetic variants between women with cervical precancerous lesions and healthy controls in Latvia.Materials and methods: From January until April 2017 we enrolled 84 consecutive patients referred for colposcopy to Riga East University Hospital (Latvia) due to abnormal cervical cytology results. 57 women who came for a regular check-up and had normal cytology smears were included in the control group. Material from the cervix was taken for subsequent HLA genotyping of 13 DRB1*, 8 DQA1*, and 12 DQB1* alleles. Colposcopy was performed on all participants. In case of visual suspicion for CIN cervical biopsy was done.Results: There were 57 “no CIN” patients, 23 histologically proven CIN 1 and 61 CIN2+ cases in the study population. CIN2+ was more often associated with DQA1*0401 (OR 6.68, 95% CI 1.47-30.29, p=0.014), DRB*15 (OR 2.99, 95% CI 1.22-7.39, p=0.017), DQB1*0401 (OR 2.91, 95%CI 1.11-7.68, p=0.03), DQA1*0103 (OR 2.72, 95% CI 1.02-7.21, p=0.045), DRB1*11 (OR 2.42, 95% CI 1.10-5.33, p=0.029) and DQB1*0301 (OR 1.94, 95% CI 1.12-3.38, p=0.018). Women with “no CIN” more often had DQB1*0501 (OR 0.17, 95% CI 0.04-0.81, p=0.026), DRB1*16 (OR 0.21, 95% CI 0.06-0.78, p=0.019), DQA1*0301 (OR 0.35, 95% CI 0.14-0.87, p=0.024) and DRB1*14 (OR 0.59, 95% CI 0.01-0.46, p=0.007).Conclusions: In the current study we have demonstrated a strong association with risk and protective HLA class II alleles that are determined by the HLA-DRB1*; DQA1*; DQB1*.

Performance of Different Follow-Up Strategies and Genotype-Based Recurrence Risk After Treatment of Cervical High-Grade Squamous Intraepithelial Lesion.

Our aim was to evaluate the performance of different follow-up strategies after treatment for cervical intraepithelial neoplasia (CIN) 2 or 3, including human papillomavirus (HPV) detection, cytology, or colposcopy, as well as their combinations. Additionally, we compared the influence of the persistence of HPV 16/18 versus that of other high-risk HPV genotypes (HR-HPV) in the recurrence risk. Retrospective register-based study, including women who had an excision of the transformation zone for CIN2 or CIN3 at our institution, between January 2011 and December 2022. The outcome assessed was histopathological recurrence/persistence of CIN2 or worse. Of the 721 women included, 6.8% (49/721) had recurrence/persistence. The sensitivity, specificity, and positive and negative predictive values of the HPV test were 97.4%, 80%, 22.3%, and 99.8%, respectively, whereas for cotesting (HR-HPV and cytology), 86.8%, 90.1%, 34.4%, and 99.1%, respectively. The referral rates for colposcopy were 24.3% and 14.2%, respectively. The sensitivity of colposcopy was low (40.0%).Women who were initially positive for non-16/18 genotypes at baseline who became HPV16/18 positive during follow-up, had a statistically significant increased risk of CIN2 or worse, compared with those who tested positive only for other HR-HPV genotypes during both stages (hazard ratio = 4.98; 95% CI = 1.66-14.91). Human papillomavirus testing is the best strategy for follow-up after treatment of cervical HSIL. The addition of cytology triage decreases by more than 40% the referrals for colposcopy, without significantly missing cases of recurrence/persistence. Human papillomavirus 16/18 in the follow-up, regardless of being previously positive, is associated with higher risk of recurrence/persistence of HSIL.

Cervical Cancer Treatment Update: A Society of Gynecologic Oncology Clinical Practice Statement

ABSTRACT Despite increased screening and human papillomavirus (HPV) vaccination in high-income countries, cervical cancer represents the fourth most diagnosed cancer in women worldwide and the second highest cause of cancer mortality among women in low- and middle-income countries. This clinical practice statement describes therapies for cervical cancer by treatment setting, as well as quality of life, financial toxicity, and disparities associated with the disease. Persistent HPV infection, particularly types 16 and 18, are the main factor in the development of cervical cancer. High-risk HPV variants integrate HPV DNA into the host genome to upregulate two viral oncoproteins, E6 and E7, which in turn inhibit the tumor suppressor proteins p53 and Rb. Certain driver mutations including PIK3CA, KRAS, and EGFR are frequently seen in cervical cancer, however further research is needed to identify an actionable biomarker based on targetable oncogenic alterations. Locally advanced cervical cancer is defined as clinically visible tumor exceeding 4 cm or invading beyond the cervix, extending to the pelvic sidewalls, vagina, bladder, rectum, or involving pelvic and/or paraaortic lymph nodes. Standard treatment for locally advanced cervical cancer is external beam radiation therapy and concurrent weekly cisplatin. Standard treatment for advanced, recurrent, or metastatic cervical cancer is cisplatin, paclitaxel, and bevacizumab (possibly adding pembrolizumab). Several studies have shown that checkpoint inhibitors, when combined or sequenced with chemoradiation, may provide survival benefit in both locally advanced and recurrent/metastatic cervical cancer. Given these findings, immunotherapy should be incorporated in treatment of advanced or recurrent disease. Negative effects on quality of life (QOL) in patients with cervical cancer often begin in people who receive negative Papanicolaou test results or positive HPV DNA tests. Negative body image, self-esteem, and relationships with partners contribute to an overall decrease in QoL. Surgical, radiation-induced, and chemotherapy-induced treatment effects further impact survivors’ physical health, body-image, and sexual function. Economic burdens of cancer diagnosis and treatment may disproportionally affect cervical cancer patients due to the intensity of curative treatment, decreases in QoL and functional status, and unique population including younger patients, those with poor access to health care at baseline, and those who identify as racial or ethnic minorities.

Escherichia coli and HPV16 coinfection may contribute to the development of cervical cancer

ABSTRACT Persistent human papillomavirus HPV infection is a necessary but insufficient condition for cervical cancer. Microorganisms are crucial environmental factors in cancers susceptibility and progression, recently attracting considerable attention. This study aimed to determine the infection status and relationship between high-risk HPV (HR-HPV) and lower genital tract infectious pathogens in cervical cancer and its precursors. From a retrospective and a prospective cohort analysis, Escherichia coli (E. coli) dominated the pathogens isolated from cervical discharges, and an isolation rate uptrend has been shown recently. HPV16 and E. coli’s coinfection rate gradually increased with the severity of cervical intraepithelial neoplasia. The adhesion and invasion abilities of the isolated E. coli to HPV16-positive SiHa cells were evaluated in vitro. The TCGA database and cervical tissues samples analysis showed that IL-10 was upregulated in cervical cancer. IL-10 expression levels increased in tissue samples with the severity of cervical cancer and its precursors with HPV16 and E. coli coinfection. Although no significant changes in IL-10 production were observed in the co-culture supernatant, we hypothesized that Treg immune cells in the tumour microenvironment might be responsible for the local IL-10 upregulation, according to our data showing Foxp3 upregulation and an upward trend with the cervical intraepithelial neoplasia grading to cancer and tumours with E. coli and HPV16 coinfection. Our data provide insights into the possible role of E. coli in cervical cancer progression and suggest that the application of HPV and E. coli screening programs may be an effective strategy to relieve the burden of cervical cancer and its precursor lesions.

Evaluation of the Association between Genetic Polymorphism of Interleukin-1 Beta (–511C/T and +3953C/T) and Cervical Cancer Susceptibility

Cervical cancer (CC) is the leading cause of cancer-related mortality among women, primarily caused by persistent human papillomavirus (HPV) infection, especially in developing countries. A proinflammatory cytokine, emerging as a major facilitator of carcinogenesis, is termed interleukin-1 beta (IL-1β), which characterizes host-environment interactions. Numerous epidemiological studies have revealed that IL-1β gene polymorphisms have been associated with numerous malignancies, but in the context of CC, results of these studies were inconclusive. Thus, our study aimed to explore the relationship between IL-1β polymorphisms (-511C/T and +3953C/T) and CC susceptibility. Genotyping was conducted on 192 CC patients and 200 healthy controls through polymerase chain reaction-restricted fragment length polymorphism. HPV analysis was done through real-time polymerase chain reaction, and the serum concentration of IL-1β was measured by enzyme-linked immunosorbent assay. Women with CT and TT genotypes of IL-1β -511C/T had a threefold increased risk of CC (odds ratio [OR], 3.60; 95% confidence interval [CI], 2.132-6.063; p &lt; 0.001 vs. OR, 3.34; 95% CI, 1.952-5.713; p &lt; 0.001) compared to controls. Women with the T allele of IL-1β -511C/T polymorphism were associated with increased CC susceptibility (OR, 2.00; 95% CI, 1.51-2.66; p = 0.0001) compared to controls. No significant difference was found between patients and controls in the genotype or allele frequencies of IL-1β +3953C/T polymorphism (OR, 0.93; 95% CI, 0.56-1.55; p = 0.86 vs. OR, 0.95; 95% CI, 0.72-1.26; p = 0.74). There was no significant association found between IL-1β -511C/T promoter (OR, 2.41; 95% CI, 0.46-12.76; p = 0.28 vs. OR, 1.64; 95% CI, 0.13-21.10; p = 0.7) and +3953C/T (OR, 3.76; 95% CI, 0.44-31.82; p = 0.19 vs. OR, 0.21; 95% CI, 0.01-3.92; p = 0.25) polymorphisms in tobacco chewers and smokers compared to controls. The level of serum concentration of IL-1β was significantly higher in cases compared to controls. Our results conclude that IL-1β -511C/T polymorphism is associated with CC susceptibility.

Vaginal pH value can affect the susceptibility to human papillomavirus infection

BackgroundCervical cancer is the fourth most common cancer among women, with persistent high-risk human papillomavirus (HPV) infection being responsible for its progression. In healthy, pre-menopausal women, the vaginal pH value is maintained at 3.8–4.5, but various factors can affect it. Previous studies have suggested the relationship between vaginal pH value and HPV infection. In this study, we aimed to explore the relationship between vaginal pH and susceptibility of HPV infection.MethodsIn our study, we retrospectively collected medical information from women who underwent leukorrhea examination at our hospital. We excluded women with infectious diseases or cancer, those who were pregnant or within 6 months post-delivery, and those without HPV test results within 6 months. The association between percentage of HPV infection and vaginal pH value was analyzed. Furthermore, we prepared HPV pseudovirus (PsVs) by co-transfecting structure plasmids and report plasmids in 293FT cells. In vitro, we changed the pH value of cell culture medium to investigate its influence on HPV PsVs infection. In vivo, we changed mouse’s vaginal pH value to investigate its influence on HPV PsVs infection.ResultsOur retrospective study included 3115 women aged 20–78, including 2531 women with HPV negative and 584 women with HPV positive. The percentages of both HPV infection and high-risk HPV infection were higher in women with a vaginal pH value ≥5.0 compared to those with a pH value < 5.0. In vitro, HPV PsVs infection rate was higher in cell culture medium of higher pH value, dominantly due to the influence of pH value on the stage of HPV PsVs adhering to cell surface. Neither of the cell surface HPV receptors Syndecan-1 nor integrin α6 was found to be changed obviously in different pH values. In vivo, more HPV PsVs were adhered to the mouse’s vaginal epithelial cells with the increase of the vaginal pH value.ConclusionsOur study suggests a possible association between vaginal pH value and HPV infection. The pH value can influence the susceptibility of HPV PsVs infection by affecting the adhering of HPV PsVs to cells in vivo and in vitro. Additionally, the cell surface HPV receptors Syndecan-1 and Integrin α6 do not seem to be affected by pH value, and the specific mechanism needs to be further explored.

Investigation of the relationship between the changes in vaginal microecological enzymes and human papillomavirus (HPV) infection.

This study aims to investigate the relationship between the human papillomavirus (HPV) infection and the altered vaginal microecological environment of patients. Initially, HPV genotyping and microecological detection were performed in 1281 subjects in the Department of Obstetrics and Gynecology of The First Hospital of Qinhuangdao (Qinhuangdao, China). The relationship between the enzymes of vaginal microecology, that is, proline aminopeptidase and acetylglucosaminidase, and vaginal inflammatory diseases, as well as the prognosis of HPV infection, was analyzed. The experimental findings indicated a close relationship between the expression of positive prolyl aminopeptidase and trichomonas vaginitis, as well as bacterial vaginitis. In addition, the expression of acetylglucosaminidase is closely associated with trichomonas vaginitis and vulvovaginal candidiasis. Furthermore, the observations indicated that positive prolyl aminopeptidase and acetylglucosaminidase could increase the risk of various subtypes of HPV infection in patients. The receiver operating characteristic curve analysis presented that the expression of prolyl aminopeptidase and acetylglucosaminidase could offer exceptional diagnostic efficacy, indicating their association with persistent HPV infection. In summary, our results highlighted that the expression of positive prolyl aminopeptidase and acetylglucosaminidase in the vaginal microecology could be substantially correlated to the occurrence and the development of vaginal inflammatory diseases, as well as the outcome and the risk of persistent HPV infection.

Precision Population Cancer Medicine in Cancer of the Uterine Cervix: A Potential Roadmap to Eradicate Cervical Cancer.

With the success of the Human Genome Project, the era of genomic medicine (GM) was born. Later on, as GM made progress, there was a feeling of exhilaration that GM could help resolve many disease processes. It also led to the conviction that personalized medicine was possible, and a relatively synonymous word, precision medicine (PM), was coined. However, the influence of environmental factors and social determinants of diseases was only partially given their due importance in the definition of PM, although more recently, this has been recognized. With the rapid advances in GM, big data, data mining, wearable devices for health monitoring, telemedicine, etc., PM can be more easily extended to population-level health care in disease management, prevention, early screening, and so on.and the term precision population medicine (PPM) more aptly describes it. PPM's potential in cancer care was posited earlier,and the current authors planned a series of cancer disease-specific follow-up articles. These papers are mainly aimed at helping emerging students in health sciences (medicine, pharmacy, nursing, dentistry, public health, population health), healthcare management (health-focused business administration, nonprofit administration, public institutional administration, etc.), and policy-making (e.g., political science), although not exclusively. This first disease-specific report focuses on the cancer of the uterine cervix (CC). It describes how recent breakthroughs can be leveraged as force multipliers to improve outcomes in CC - by improving early detection, better screening for CC, potential GM-based interventions during the stage of persistent Human papillomavirus (HPV) infection and treatment interventions - especially among the disadvantaged and resource-scarce populations. This work is a tiny step in our attempts to improve outcomes in CC and ultimately eradicate CC from the face of the earth.

High-risk HPV prevalence and vaccination coverage among Indigenous women in the Colombian Amazon: Implications for cervical cancer prevention. Cross-sectional study.

Cervical cancer, primarily caused by Human Papillomavirus (HPV) transmission through sexual contact, necessitates comprehensive strategies to combat its impact on women's health. Yet, certain underserved populations, such as low socioeconomic and ethnic minority groups, encounter barriers in accessing timely interventions and early diagnosis. This cross-sectional study was conducted with the aim of assessing HPV prevalence, genotype distribution, and co-infections among 280 adult women residing in a Colombian Indigenous Reserve within the Amazon region. The research adhered to a community-centric approach that respected cultural norms, native languages, and Indigenous authorities' permission. The study revealed an overall HPV infection prevalence of 31.1% (n = 87, 95% CI 25.7-36.8), with 22.5% (n = 63, 95% CI 17.7-27.8) of women infected by at least one high-risk HPV genotype and 15.0% (n = 42, 95% CI 11-19.7) infected by at least one LR genotype. These results align with the findings of other Colombian studies. Notable high-frequency genotypes included 16, 52, 66, 56, and 68, with the most common combinations being [66-52] and [66-58]. The study also assessed the prevalence of HPV vaccination, revealing a rate of 22.9%, lower than the national average. In vaccinated women, the prevalence of genotypes 16 and 18 was significantly reduced, as anticipated. Importantly, it was observed that 57.1% of all high-risk HPV infections could have been prevented with the use of the nonavalent vaccine. These findings underscore the critical need to enhance adherence to early cervical cancer detection and monitor positive cases to evaluate high-risk HPV persistence. Efforts should be directed toward continuing vaccination coverage against high-risk HPV 16 and 18 with the quadrivalent vaccine, while also striving to make the nonavalent vaccine accessible for inclusion in large-scale public health programs. Additionally, the study did not identify a specific pattern of co-infection. The study emphasizes the significance of adopting a locally tailored epidemiological approach to guide and promote cervical cancer prevention efforts in Indigenous communities.