Persistent High-risk Human Papillomavirus Infection Research Articles

Incidence, clearance, persistence and factors related with high-risk anal HPV persistence in South-East Asian MSM and transgender women.

Persistent anal high-risk human papillomavirus (HR-HPV) infection is a major risk factor for anal cancer among MSM and transgender women (TGW). We aimed to estimate incidence, clearance, and persistence of anal HR-HPV in HIV-positive and HIV-negative MSM and TGW, and to assess factors for HR-HPV persistence. Prospective cohort study. MSM and TGW aged at least 18 years, were enrolled from Indonesia, Malaysia, and Thailand, then followed up 6-monthly for 12 months. Anal swabs were collected at every visit for HR-HPV genotypes to define anal HR-HPV incidence, clearance, and persistence. Logistic regression was used to evaluate factors associated with HR-HPV persistence. Three hundred and twenty-five MSM and TGW were included in this study, of whom 72.3% were HIV-positive. The incidence of anal HR-HPV persistence was higher in HIV-positive than HIV-negative MSM participants (28.4/1000 vs. 13.9/1000 person-months). HIV-positive participants had HR-HPV lower clearance rate than HIV-negative participants (OR 0.3; 95% CI 0.1-0.7). The overall persistence of HR-HPV was 39.9% in HIV-positive and 22.8% HIV-negative participants. HPV-16 was the most persistent HR-HPV in both HIV-positive and HIV-negative participants. HIV infection (aOR 2.87; 95% CI 1.47-5.61), living in Kuala Lumpur (aOR 4.99; 95% CI 2.22-11.19) and Bali (aOR 3.39; 95% CI 1.07-10.75), being employed/freelance (aOR 3.99; 95% CI 1.48-10.77), and not being circumcised (aOR 2.29; 95% CI 1.07-4.88) were independently associated with anal HR-HPV persistence. HIV-positive MSM and TGW had higher risk of persistent anal HR-HPV infection. Prevention program should be made available and prioritized for HIV-positive MSM and TGW where resources are limited.

Genetic predisposition for cervical cancer

Aim: to assess a role of genetic factors and human papillomavirus (HPV) in developing cervical neoplasia based on analyzing current publications on virus-induced carcinogenesis.Materials and methods. A systematic overview on publications dedicated to examining genetic predisposition to developing cervical cancer (CC) available in electronic databases was performed by searching in the International Scientific Databases (ISDB) PubMed/MEDLINE as well as manually by accessing enlisted input documents related to the above noted studies. Full-text publications were solely selected for analysis.Results. CC is a multifactorial disease implicating host genetic predisposition being caused by persistent high oncogenic risk HPV-infection. Immune system plays a major role in HPV-infection. Altered cell-mediated immune response is responsible for impaired potential to HPV eradication. On the other hand, immune evasion contributes to viral persistence and cancer progression. Oncogenes, cancer suppressor genes (Rb and TP53), cytokine (ILs, IFNG) and chemokine (CXCL) genes, the genes involved in antigen processing, as well as an impact for each gene polymorphism or even haplotypes playing a role in cervical carcinogenesis are mainly involved in CC developing.Conclusion. The data obtained allowed to demonstrate a role for genetic polymorphisms in the genes encoding cytokines, chemokines, diverse receptors as well as those involved in antigen processing, and cancer suppressor genes in perpetuation of HPV-infection.

The role of body mass index in incidence and persistence of cervical human papillomavirus infection

PurposeThis study aimed to assess the association between body mass index and incident or persistent cervical high-risk human papillomavirus (hrHPV) infection. MethodsThis cohort study included 6809 women from the general Danish population who participated in two clinical visits (in 1991–1993 and in 1993–1995). Height and weight were measured by nurses, lifestyle data were obtained by structured interviews, and cervical cytology samples were obtained for hrHPV DNA testing. We conducted log-binomial regression to estimate risk ratios (RRs) with 95% confidence intervals (CIs) of incident and type-specific persistent hrHPV infection according to body mass index, adjusting for age, education, smoking, and the number of sexual partners in the past year. ResultsWe found no increased risk of incident hrHPV infection in women who were underweight (RRadjusted, 0.97; 95% CI, 0.64–1.48), overweight (RRadjusted, 0.98, 95% CI, 0.82–1.17), or obese (RRadjusted, 0.93; 95% CI, 0.63–1.36) compared with women of normal weight. The risk of hrHPV persistence was similar in overweight (RRadjusted, 0.98; 95% CI, 0.71–1.34) and obese (RRadjusted, 1.00; 95% CI, 0.56–1.79) women compared with women of normal weight, whereas underweight women had a lower risk (RRadjusted, 0.32; 95% CI, 0.11–0.95). ConclusionsOverweight and obesity were not associated with HPV incidence or persistence when adjusting for sexual behavior.

Measuring vaccine effectiveness against persistent HPV infections: a comparison of different statistical approaches

BackgroundPersistent high-risk human papillomavirus (HPV) infection is endorsed by the World Health Organization as an intermediate endpoint for evaluating HPV vaccine effectiveness/efficacy. There are different approaches to estimate the vaccine effectiveness/efficacy against persistent HPV infections.MethodsWe performed a systematic literature search in Pubmed to identify statistical approaches that have been used to estimate the vaccine effectiveness/efficacy against persistent HPV infections. We applied these methods to data of a longitudinal observational study to assess their performance and compare the obtained vaccine effectiveness (VE) estimates.ResultsOur literature search identified four approaches: the conditional exact test for comparing two independent Poisson rates using a binomial distribution, Generalized Estimating Equations for Poisson regression, Prentice Williams and Peterson total time (PWP-TT) and Cox proportional hazards regression. These approaches differ regarding underlying assumptions and provide different effect measures. However, they provided similar effectiveness estimates against HPV16/18 and HPV31/33/45 persistent infections in a cohort of young women eligible for routine HPV vaccination (range VE 93.7–95.1% and 60.4–67.7%, respectively) and seemed robust to violations of underlying assumptions.ConclusionsAs the rate of subsequent infections increased in our observational cohort, we recommend PWP-TT as the optimal approach to estimate the vaccine effectiveness against persistent HPV infections in young women. Confirmation of our findings should be undertaken by applying these methods after longer follow-up in our study, as well as in different populations.

Prevalence characteristics of cervical human papillomavirus (HPV) infection in the Zhoupu District, Shanghai City, China

BackgroundHuman papillomavirus (HPV) infection is the leading cause of genital diseases. It can cause a series of cervical lesions. The distribution of HPV genotypes indicates that the increased prevalence of high-risk HPV (HR-HPV) is positively correlated with the severity of cervical lesions. In addition, persistent HR-HPV infection is associated with the risk of cervical cancer. Considering the latest approval of homemade HPV vaccine in China and the prevalence of HPV distribution, this is of great significance for guiding HPV vaccination work.ObjectiveOur study’s purpose was to examine trends of cervical HPV infection rate in each 5-year age group from 2011 to 2019.MethodsRetrospective analysis of human papillomavirus prevalence rate of 59,541 women from 2011 to 2019 in the District Zhoupu of Shanghai City in China. HPV genotype testing is performed using a commercial kit designed to detect 15 high-risk HPV genotypes and 6 low-risk HPV genotypes. Trends were examined for each 5-year age group.ResultsIn the District Zhoupu of Shanghai City in China, the prevalence rate of cervical HPV increased significantly among women aged 15–34 years. The most prevalent HR-HPV genotypes were 52, 16, 58, 53, 39, and 51.ConclusionCervical HPV prevalence rate is very high in younger women in suburb Shanghai. Due to significant differences in infection rates between specific age groups and HPV subtypes, timely intervention is required for these vulnerable populations.

Photodynamic therapy combined with carbon dioxide laser for low-grade vaginal intraepithelial neoplasia: A retrospective analysis.

To evaluate the clinical efficacy and safety of 5-aminolevulinic acid photodynamic therapy (ALA-PDT) combined with a carbon dioxide laser (CO2 laser + PDT) versus CO2 laser for the treatment of low-grade vaginal intraepithelial neoplasms (vaginal LSIL). We recruited 40 patients with vaginal LSIL and persistent HR-HPV infection and divided these individuals into two groups. The CO2 laser + PDT group (20 patients) received one CO2 laser treatment and three treatments of ALA-PDT over a one-week interval. The CO2 laser group (20 patients) received up to three CO2 laser treatments. All patients were followed up at 1 month, 3 month, 6 month and 1 year. Hybrid capture HPV DNA assay and colposcopic biopsy were performed for both groups before treatment and during each of the follow-ups. Adverse effects were also assessed. The complete remission (CR) rates were 65 % (13/20) in the CO2 laser group and 85 % (17/20) in the CO2 laser + PDT group (p > 0.05). HR-HPV remission rates were 25 % (5/20) in the CO2 laser group and 95 % (19/20) in the CO2 laser + PDT group (p < 0.05) at one year after treatment. In the CO2 laser group, one patient experienced severe bleeding during treatment. Twelve patients had varying degrees of adhesions and vaginal scar stenosis. One patient underwent vaginal "dead angle" after repeated CO2 laser treatment. No severe adverse events or systemic side effects were observed in the CO2 + PDT group. Topical ALA-PDT combined with CO2 laser is an effective, safe, and well-tolerated treatment for vaginal LSIL and HR-HPV infections.

Abstract A20: Persistent high-risk HPV infection in the development of uterine cervical cancer

Abstract The early detection and treatment of preneoplastic uterine cervical lesions is certainly a major challenge for developing countries. Preneoplastic lesions result from human papilloma virus (HPV) infection in cells located in the transformation zone of the cervical epithelial tissue, causing low-grade or high-grade lesions. HPV infections are transient and most of the time cleared within a couple of years following exposure. However, 10–20% of infections persist latently, leading to disease progression and, ultimately, various forms of invasive cancer. The transformation of preneoplastic lesions in invasive cancer cells is provoked at least partly by HPV, especially through gene and protein expression modulation. This modulation involves tissue oxygenation, oncogene activation, loss of tumor suppressor genes and aberrant molecular signaling pathways (such as Insulin-like growth factor-1 receptor (IGF-1R). In recent studies, it was reported that IGF1R is overexpressed by effect of E6 AA-a and E-G350 HPV-16 variants. The aim of the present study was to prospectively and retrospectively report the detection of HPV-16 variants and IGF1R expression in patients with cervical cancer and assess the relationship with development of uterine cervical cancer. Sixty consecutive patients with invasive cervical cancer were assessed for HPV-16. A total of 35 patients (58.3%) were infected with HPV-16, with a mean age of 51 years (range: 30–76 years). Thirty patients (85.7%) were diagnosed with European HPV-16 variant and five patients (14.3%) were diagnosed with non-European HPV-16 variants. European HPV-16 variants (E-HPV-16) were mainly E-G350 (n = 14; 41.1%) and E-T350 (n = 12; 35.2%) subclasses. Of these 35 patients, 15 received exclusive radiotherapy and four radiochemotherapy, and the remaining 16 did not complete the treatment (NCT). Of the patients who presented an incomplete response, overexpression of IGF1R was detected in all. Of patients NCT, we retrospectively studied one case in IIIB stage FIGO. Samples of preneoplastic lesions and invasive cervical cancer were analyzed to confirm histopathologic diagnosis and detect the presence of HPV variants and overexpression of IGF-1R. Of the results found in this case, in which the patient was diagnosed in 1986 with a high-grade squamous intraepithelial cervical lesion, HPV-16 E-G350 and HPV-33 coinfection as low expression of IGF1R were detected and for the invasive cancer diagnosed in 2002, the presence of HPV-16 AA-c and overexpression of IGF1R was detected. The detection of high-risk HPV in samples of preneoplastic lesions and invasive cancer in a 60-year-old patient at the time of diagnosis showed that HPV33 infection was eliminated. Results such as these suggest that persistent infection with HPV-16 variants, overexpression of IGF1R, such as viral load and age, could be necessary factors for disease progression, and thus contribute to the identification of patients with a high risk of viral persistence and development of cervical neoplasia. Note: This abstract was not presented at the conference. Citation Format: Pablo Moreno Acosta, Diana Mayorga, Nicolas Magné. Persistent high-risk HPV infection in the development of uterine cervical cancer [abstract]. In: Proceedings of the AACR Special Conference on the Microbiome, Viruses, and Cancer; 2020 Feb 21-24; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2020;80(8 Suppl):Abstract nr A20.

Multiple HPV Infections and Viral Load Association in Persistent Cervical Lesions in Mexican Women.

Persistent high-risk human papillomavirus (HR-HPV) infections play a major role in the development of invasive cervical cancer (CC), and screening for such infections is in many countries the primary method of detecting and preventing CC. HPV typing can be used for triage and risk stratification of women with atypical squamous cells of undetermined significance (ASC-US)/low-grade cervical lesions (LSIL), though the current clinical practice in Mexico is to diagnose CC or its preceding conditions mainly via histology and HR-HPV detection. Additional information regarding these HPV infections, such as viral load and co-infecting agents, might also be useful for diagnosing, predicting, and evaluating the possible consequences of the infection and of its prevention by vaccination. The goal of this follow-up hospital case study was to determine if HPV types, multiple HPV infections, and viral loads were associated with infection persistence and the cervical lesion grade. A total of 294 cervical cytology samples drawn from patients with gynecological alterations were used in this study. HPV types were identified by real-time PCR DNA analysis. A subset of HPV-positive patients was reevaluated to identify persistent infections. We identified HPV types 16, 18, and 39 as the most prevalent. One hundred five of the patients (59%) were infected with more than one type of HPV. The types of HPV associated with multiple HPV infections were 16, 18, and 39. In the follow-up samples, 38% of patients had not cleared the initially detected HPV infection, and these were considered persistent. We found here an association between multiple HPV infections and high viral loads with and infection persistence. Our findings suggest there are benefits in ascertaining viral load and multiple HPV infections status of HR-HPV infections for predicting the risk of persistence, a requirement for developing CC. These findings contribute to our understanding of HPV epidemiology and may allow screening programs to better assess the cancer-developing risks associated with individual HR-HPV infections.

Role of Oct3/4 in Cervical Cancer Tumorigenesis.

Cervical cancer (CC) is the fourth most common type of cancer that affects women. Compared to other types of cancer, CC has a high mortality rate in women worldwide. Several factors contribute to the development of CC, but persistent high-risk human papillomavirus infection is the main etiologic agent associated with the development of CC. Moreover, several studies reported that alterations in the expression of transcription factors present in a small subpopulation of cells within tumors called cancer stem cells (CSCs), which contribute to the development of CC by promoting tumorigenicity and metastasis. These transcription factors affect self-renewal and maintenance of pluripotency and differentiation in stem cells. OCT3/4 belongs to the family of transcription factors with the POU domain. It consists of five exons and can be edited by alternative splicing into three main transcripts: OCT3/4A, OCT3/4B, and OCT3/4B1. The OCT3/4 expression in CSCs promotes carcinogenesis and the development of malignant tumors, and the loss of expression leads to the loss of self-renewal and proliferation and favors apoptosis. This review describes the main roles of OCT3/4 in CC and its importance in several biological processes that contribute to the development of CC and may serve as molecular targets to improve prognosis of CC.

Composition of the Vaginal Microbiome Associated with High Risk HPV Infection and Increased Risk for Cervical Cancer

Abstract Persistent high-risk Human papillomavirus (HPV) is a necessary but not sufficient cause for development of cervical cancer. Changes in the vaginal microbiota including reduction of Lactobacillus and increased microbial diversity may facilitate HPV infection and persistence as well as the pathogenesis of cervical cancer. Our objective was to characterize the vaginal microbiota among women with and without persistent HPV infection with HPV 6, 11, 16, 18, 31, 33, 45, 52, 58 in a cohort of young U.S. women. Methods: This analysis used data from a longitudinal study of 1365 women followed for 12 months every two months apart from six locations across the US. HPV genotyping was performed using quantitative PCR using TaqMan probes in a customized plate (ThermoFisher Scientific). Bacterial communities were profiled by 16S rRNA gene sequences from the V3-V4 region using high-throughput pyrosequencing. Persistence was defined by examining for HPV presence in two consecutive visits. Results: Participants included 80 African-American women tested at 3 consecutive time-points. The mean age of participants was 21.4 years. About 43.7% (95% CI: 32.7%–55.3%) had persistent HPV infection, 20% (11.9%–30.4%) were able to clear the infection, and 36.2% (25.8%–47.8%) were consistently negative for HPV infection at all three time points. Atopobium and Peptoniphilus were significantly more abundant in women who were HPV negative suggesting possible protective effects. Prevotella bivia was enriched among women with persistent HPV. Conclusion: Based on these data, we can hypothesize that Prevotella richness is significantly associated with HPV persistence, suggesting a possible role in chronic HPV infection and development of cervical cancer.

Hyperbranched poly(β-amino ester) based polyplex nanopaticles for delivery of CRISPR/Cas9 system and treatment of HPV infection associated cervical cancer

Persistent high-risk HPV infection is the main factor for cervical cancer. HPV E7 oncogene plays an important role in HPV carcinogenesis. Down-regulation of E7 oncogene expression could induce growth inhibition in HPV-positive cells and thus treats HPV related cervical cancer. Here we developed a non-virus gene vector based on poly(amide-amine)-poly(β-amino ester) hyperbranched copolymer (hPPC) for the delivery of CRISPR/Cas9 system to specifically cleave HPV E7 oncogene in HPV-positive cervical cancer cells. The diameter of polyplex nanoparticles (NPs) formed by hPPCs/linear poly(β-amino ester) (PBAE) and plasmids were approximately 300 nm. These hPPCs/PBAE-green fluorescence protein plasmids polyplex NPs showed high transfection efficiency and low toxicity in cells and mouse organs. By cleaving HPV16 E7 oncogene, reducing the expression of HPV16 E7 protein and increasing intracellular retinoblastoma 1 (RB1) amount, hPPCs/PBAE-CRISPR/Cas9 therapeutic plasmids polyplex NPs, especially highly branched hPPC1-plasmids polyplex NPs, exhibited strong growth inhibition of cervical cancer cells in vitro and xenograft tumors in nude mice. Together, the hPPCs/PBAE polyplex NPs to deliver HPV16 E7 targeted CRISPR/Cas9 system in this study could potentially be applied to treat HPV-related cervical cancer.

Research of the potential biomarkers in vaginal microbiome for persistent high-risk human papillomavirus infection

Vaginal dysbiosis may paly role in increased risk of human papillomavirus (HPV) infection. This study aims to explore potential vaginal microbiome biomarkers, to predict persistent high-risk HPV (HR-HPV) infection and cervical intraepithelial neoplasia (CIN) 2+, and to find novel treatment targets for HPV infection. A total of 329 women aged 20-69 were enrolled in this study, including 59 with cervical persistent HPV infection irrespective of cytology status (group A), 139 with incident HPV infection (group B), and 131 without HPV infection (group C). Vaginal microbiome composition was determined by sequencing of barcoded 16S rDNA gene fragments (V4) on Illumina HiSeq2500. In genus level, the relative abundance of Prevotella, Porphyromonas and Enterococcus were significantly the highest in group A, while Bacteroides was the lowest in group A. In species level, we found the relative abundance of Prevotella bivia, Enterococcus durans and Porphyromonas uenonis were the highest in group A while Lactobacillus iners was significantly under-represented in group A than the other two, and Prevotella disiens was over-represented in group C than the other two groups. A predominance of Prevotella bivia, Enterococcus durans and Porphyromonas uenonis with a concomitant paucity of Lactobacillus iners and Prevotella disiens may relate to HPV persistent infection. Furthermore, the relative abundance of Prevotella bivia being over 0.05554% with Prevotella disiens being under 0.02196% may be a good predictor for appearance CIN2+ for those diagnosed with the other 12 types of HR-HPV persistent infection but normal ThinPrep cytology test (TCT) testing. The exact molecular mechanism of the vaginal microbiome in the course of persistent HR-HPV infection and cervical neoplasia should be further explored. Future research should include intervention of vaginal microbiome composition to reverse the course of HR-HPV infection and the natural history of cervical neoplasia.

Rapid and non-invasive screening of high-risk human papillomavirus using Fourier transform infrared spectroscopy and multivariate analysis

Persistent high-risk human papillomavirus (HR-HPV) infection is leading cause for the occurrence of cervical cancer, and timely detection and early treatment of HR-HPV infection can effectively reduce incidence of cervical cancer. In this study, a rapid and non-invasive method for detecting HR-HPV was proposed by using Fourier transform infrared (FT-IR) spectra of cervical exfoliated cells combined with multivariate analysis. A total of 100 spectra were recorded from 50 HR-HPV positive patients and 50 normal subjects. The obvious difference in infrared spectrum between the two groups was mainly shown at 1042 cm−1 (mucin), 1246 cm−1 (amide III), 1396 cm-1 (proteins), 1543 cm−1 (amide II), 1651 cm−1 (amide I), 2361 cm−1 (CO2), 2928 cm−1 (lipids), and 3294 cm−1 (amide A). Then, a principal component analysis-linear discriminant analysis (PCA-LDA) diagnostic model was developed and applied on the FT-IR spectra of normal samples as well as HR-HPV positive patients, and satisfactory classification results were obtained. The diagnostic accuracy, specificity, and sensitivity were 98 %, 98 %, and 98 %, respectively. Furthermore, the area under the receiver operating characteristic (ROC) curve (AUC) was 0.997, which could further demonstrate the feasibility of the PCA-LDA model. Therefore, our exploratory work shows that the combination of FT-IR spectroscopy and PCA-LDA model has great potential for HR-HPV screening.

Analysis of therapeutic effect of cervical radiofrequency ablation on persistent HR-HPV infection

Analysis of therapeutic effect of cervical radiofrequency ablation on persistent HR-HPV infection

Human papillomavirus infection and cervical dysplasia in HIV-positive women: potential role of the vaginal microbiota.

To assess the associations between microbiological markers of vaginal dysbiosis and incident/cleared/type-swap/persistent high-risk human papillomavirus (hrHPV) infection; and incident/cured/cleared/persistent high-grade cervical intraepithelial neoplasia (CIN2+) while controlling for persistent hrHPV infection. Two nested case-control studies (N = 304 and 236) within a prospective cohort of HIV-positive women in Johannesburg, South Africa. Participants were examined for hrHPV type (INNO-LiPA), cervical dysplasia (histology), and vaginal microbiota (VMB) composition (V3-V4 Illumina HiSeq 2x300 bp) at baseline and endline, a median of 16 months later. Women with incident hrHPV compared to those who remained hrHPV-negative were less likely to have an optimal Lactobacillus crispatus or jensenii-dominated VMB type at end-line [relative risk ratio (RRR) 0.125, P = 0.019], but not at baseline. Having different hrHPV types at both visits was associated with multiple anaerobic dysbiosis markers at baseline (e.g. increased bacterial vaginosis-associated anaerobes relative abundance: RRR 3.246, P = 0.026). Compared to women without CIN2+, but with hrHPV at both visits, women with incident CIN2+ had increased Simpson diversity (RRR 7.352, P = 0.028) and nonsignificant trends in other anaerobic dysbiosis markers at end-line but not baseline. These associations persisted after controlling for age, hormonal contraception, and CD4 cell count. Current hormonal contraceptive use (predominantly progestin-only injectables) was associated with increased CIN2+ risk over-and-above persistent hrHPV infection and independent of VMB composition. hrHPV infection (and/or increased sexual risk-taking) may cause anaerobic vaginal dysbiosis, but a bidirectional relationship is also possible. In this population, dysbiosis did not increase CIN2+ risk, but CIN2+ increased dysbiosis risk. The CIN2+ risk associated with progestin-only injectable use requires further evaluation.

Is focused ultrasound surgery (FUS) a new way to treat persistent high-risk HPV infection and CINI

Is focused ultrasound surgery (FUS) a new way to treat persistent high-risk HPV infection and CINI

A demographic and clinico pathological study of HPV associated cofactors in the pathogenesis of cervical cancer

Aims: Cervical carcinogenesis is a multi-step process associated with refractory infection by highrisk human papillomavirus (HPV) types. Only a minority of HPV infected women develop cervical intraepithelial neoplasia (CIN) or cervical cancer, indicating that HPV infection is not the sole risk factor to induce cervical cancer. The present study aimed to identify the association of demographic and clinic pathological factors in persistent high risk HPV infections of cervix and progression to cervical cancer in East Indian women. Materials and Methods: Study subjects comprised 71 women with histologically proven cervical cancer, and 100 women with benign cervical lesions. The case group included HPV 16 +ve subjects with malignancy. Among subjects with benign lesions, 43 were HPV 16 +ve (intermediate group) and 57 were HPV – ve (control group). Demographic factors like age at diagnosis, age at first childbirth, parity, postmenopausal status, literacy, smoking and clinic pathological factors like type of cervical cancer and grading were correlated with HPV infections and cervical cancer. HPV status and HPV Type was confirmed by PCR based method, using specific primers. Results: There was significant association between HPV +ve individuals (both cases and intermediates) and increased parity, post menopause, increased age at diagnosis, decreased age at first childbirth, illiteracy and smoking. All individuals of the case group were HPV +ve, type 16 and most had poorly differentiated and stage III squamous cell carcinoma of the cervix. Conclusion: Our study suggests that demographic factors should be taken into account when screening for HPV infectivity and cervical cancer. Keywords: Cancer cervix, Demographic factors.

Human papillomavirus and cervical cancer.

Cervical cancer is by far the most common HPV-related disease. About 99.7% of cervical cancer cases are caused by persistent genital high-risk human papillomavirus (HPV) infection. Worldwide, cervical cancer is one of the most common cancer in women with an estimated 528,000 new cases reported in 2012. Most HPV infections clear spontaneously but persistent infection with the oncogenic or high-risk types may cause cancer of the oropharynx and anogenital regions. The virus usually infects the mucocutaneous epithelium and produces viral particles in matured epithelial cells and then causes a disruption in normal cell-cycle control and the promotion of uncontrolled cell division leading to the accumulation of genetic damage. There are currently two effective prophylactic vaccines against HPV infection, and these comprise of HPV types 16 and 18, and HPV types 6, 11, 16 and 18 virus-like particles. HPV testing in the secondary prevention of cervical cancer is clinically valuable in triaging low-grade cytological abnormalities and is also more sensitive than cytology as a primary screening. If these prevention strategies can be implemented in both developed and developing countries, many thousands of lives could be saved.

Plasma expression of miRNA-21, \u2212\u2009214, \u221234a, and -200a in patients with persistent HPV infection and cervical lesions

BackgroundTo examine differences in the plasma levels of miRNA-21, − 214, −34a, and -200a in patients with persistent high-risk human papillomavirus (hr-HPV) infection or with cervical lesions of different grades.MethodsVenous blood was collected from 232 individuals to measure the plasma expression levels of miRNA-21, − 214, −34a, and -200a. The subjects included normal controls and patients with persistent hr-HPV infection, CIN1, CIN2, CIN3, or cervical cancer (n = 42, 31, 19, 54, 71, and 15 patients, respectively). Cervical conization specimens were collected from all the women. To ensure the accuracy of histopathology, three consecutive tissue sections with an identical diagnosis were selected, and dissection samples were taken from them for miRNA detection. Eligible cases met the inclusion criteria based on sample observation using the middle slice of sandwich tissue sections from the pathological tissue in accordance with the diagnosis of CIN1, CIN2 and CIN3 in 8, 29, and 26 cases, respectively. The miRNA-21, − 214, −34a, and -200a expression levels in the paraffin-embedded tissue samples were determined. The percentage of patients with a CIN2+ diagnosis at 30–49 years old was significantly different from that of those diagnosed with CIN1. The incidence of CIN2+ patients exposed to passive smoking was significantly different from that of CIN1- patients. The percentage of CIN2+ patients with three pregnancies was significantly different from that of those with CIN1, and the percentage of CIN2+ subjects with ≥4 pregnancies was significantly different from that of CIN1- patients. The number of CIN2+ patients with two or more induced abortions was significantly different from that of patients with CIN1. The percentage of CIN2+ patients who underwent a caesarean section was significantly different from that of patients with CIN. The percentage of CIN2+ patients with first-degree relatives with cancer was significantly different from that of those with CIN1. Among CIN2+ patients, the percentage with a first sexual encounter at ≤20 years old was significantly different from that of those with CIN1. The percentage of CIN2+ patients with ≥2 sexual partners was significantly different from that of CIN1- patients.ResultsThe plasma miRNA-214, −34a, and -200a expression levels were decreased in patients with more severe cervical lesions. Plasma miRNA levels in CIN1- patients were significantly different from those in CIN2+ patients. The kappa values for miRNA-21, − 214, −34a and -200a in tissue versus plasma were 0.7122, 0.9998, 0.8986 and 0.7458, respectively. The sensitivity of each biomarker for detecting CIN2 was calculated, and ROC curves of the four miRNA biomarkers were drawn. The AUC of the four plasma miRNAs was greater than 0.5, with the AUC of miRNA-21 being the largest at 0.703. The plasma miRNA expression levels exhibited at least one tie between CIN1 and CIN2. The AUCs for miRNA-21, −34a, −200a and − 214 were 0.613, 0.508, 0.615 and 0.505, respectively.ConclusionsChanges in plasma miRNA-21, − 214, −34a and -200a levels were associated with cervical lesion severity. The plasma miRNA levels in CIN1- subjects were significantly different from those in CIN2+ subjects. This analysis may help in detection of high-grade cervical lesions.

Evaluation of Cervical Intraepithelial Neoplasia Occurrence Following the Recorded Onset of Persistent High-Risk Human Papillomavirus Infection: A Retrospective Study on Infection Duration.

Objectives: Persistent high-risk human papillomavirus infection is a major factor in the development of cervical intraepithelial neoplasia and cervical cancer. However, the exact point during this infection that cervical intraepithelial neoplasia develops has eluded researchers. Therefore, we designed a study investigating infection duration between the recorded onset of persistent high-risk human papillomavirus infection and cervical intraepithelial neoplasia development.Methods: Basic descriptive statistics, including the Chi-square test and the Kaplan-Meier method, were used to retrospectively analyze data of 277 women who underwent human papillomavirus genotyping, exhibited persistent high-risk human papillomavirus infection, were cervical cytology negative at enrollment, and developed cervical intraepithelial neoplasia at some point during follow-up.Results: Mean number of cervical cytology and human papillomavirus tests was 2.31 per patient (range: 2–8). Human papillomavirus 16, 52, 58, and 33 accounted for 21.64% (132/610), 21.64% (132/610), 15.90% (97/610), and 10.66% (65/610) of infections, respectively. 42.24% (117/277) and 57.76% (160/277) of women were diagnosed with cervical intraepithelial neoplasia 1 and cervical intraepithelial neoplasia 2+ after persistent high-risk human papillomavirus infection, with mean follow-up times of 18.15 (11.81) and 19.82 (13.31) months, respectively. Cervical intraepithelial neoplasia occurred between 4 and 70 months following the recorded onset of persistent high-risk human papillomavirus infection and 73.65% (204/277) of women developed cervical intraepithelial neoplasia within 24 months.Conclusion: Human papillomavirus 16, 52, 58, and 33 were the most prevalent high-risk human papillomavirus types in a group of women in which the majority developed cervical intraepithelial neoplasia within 24 months of persistent infection.