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Cervical cancer is the fourth most common cancer in women worldwide and is caused by persistent infection with high-risk types of human papillomavirus (HPV). HPV viral load, the amount of HPV DNA in a sample, has been suggested to correlate with cervical disease severity, and with clinical outcome of cervical cancer. In this systematic review, we searched three databases (EMBASE, PubMed, Web of Science) to examine the current evidence on the association between HPV viral load in cervical samples and disease severity, as well as clinical outcome. After exclusion of articles not on HPV, cervical cancer, or containing clinical outcomes, 85 original studies involving 173 746 women were included. The vast majority (73/85 = 85.9%) reported that a higher viral load was correlated with higher disease severity or worse clinical outcome. Several studies reported either no correlation (3/85 = 3.5%), or the opposite correlation (9/85 = 10.6%); possible reasons being different categorization of HPV viral load levels, or the use of specific sampling methods. Despite variations in study design and populations, the above findings suggest that HPV viral load is correlated to clinical outcome, and may become an important biomarker for treatment selection and response monitoring for cervical cancer., (© 2024 The Author(s). Journal of Medical Virology published by Wiley Periodicals LLC.)

Cervical cancer is an important cause of death in women worldwide. About 99.7% of all cervical cancers have been related to human papillomavirus, especially types 16 and 18. Types 6 and 11 cause genital warts. We aimed to determine the prevalence of common HPV genotypes among women in the general population and women with cervical cancer. A total of 571 healthy women cytology specimens and 113 tissue samples of cervical cancer were investigated using HPV type-specific primers. HPV DNA was detected in 24% of healthy women: 3.3% were positive for high-risk HPV and 11.6% for low-risk HPV. HPV6 (9.3%) had the highest prevalence followed by HPV11 (2.3%), HPV16 (1.8%), HPV18 (1.2%), and 9.1% of samples were positive for unknown types. Among cervical cancer samples, HPV DNA was found in 78.8% including 43.4% HPV16, 8% HPV18, and 27.4% an unknown HPV type. HPV6 and HPV11 were not detected in any cervical cancer cases and 21.2% were negative for HPV. We found no association between HPV-16/18 and age in cervical cancer. The prevalence of HPV infection is relatively high in Iran without vaccination backgrounds. HPV DNA screening and vaccination programs can prevent cervical cancer and health problems caused by genital warts.

Objectives: All cervical cancers and some vulvar, vaginal and anal cancers are caused by high-risk human papillomavirus (hrHPV). However, little is known about the association between cervical HPV infection and subsequent intraepithelial neoplasia and cancer at other anogenital sites. In this prospective cohort study, we estimated the risk of vulvar, vaginal and anal intraepithelial neoplasia grade 2/3 or cancer (VIN2+, VaIN2+, AIN2+) according to cervical hrHPV status., Methods: Liquid-based cervical cytology samples were collected from 40,399 women screened against cervical cancer in Copenhagen, Denmark, during 2002-2005. Samples were tested for hrHPV using Hybrid Capture 2 (HC2) and genotyped using INNO-LiPA. We linked the cohort with Danish nationwide registries to identify cases of VIN2+, VaIN2+ and AIN2+ during up to 15 years of follow-up. We estimated age-adjusted hazard ratios (HRs) using Cox regression and cumulative incidences using Aalen-Johansen's estimator., Results: Women with cervical HPV16 infection had increased hazard of VIN2+ (HR = 2.6; 95% confidence interval [CI], 1.2-5.5), VaIN2+ (HR = 23.5; 95% CI, 6.8-81.6) and AIN2+ (HR = 3.7; 95% CI, 1.1-12.2) compared with HC2 negative women. Women with other hrHPV types than HPV16 also had increased hazard of VaIN2+ (HR = 7.1; 95% CI, 2.3-22.3) and a borderline statistically significantly increased risk of AIN2+ (HR = 2.2; 95% CI, 0.9-4.9) compared with HC2 negative women. The 10-year cumulative incidences of VIN2+, VaIN2+ and AIN2+ in women with cervical HPV16 were 0.3% (95% CI, 0.2%-0.7%), 0.2% (95% CI, 0.1%-0.5%) and 0.1% (95 CI, 0.0%-0.4%)., Conclusions: Cervical HPV16 infection is associated with increased risk of VIN2+, VaIN2+ and AIN2+., Competing Interests: Declaration of competing interest Susanne K. Kjær has received speaker's and advisory board fees from Merck, and unrestricted research grant through her institution from Merck. Thomas Iftner has received lecture fees and research grants through his institution from Hologic GmbH and Becton Dickinson GmbH. Hanna Kristina Bertoli, Louise T. Thomsen and Christian Dehlendorff report no potential conflicts of interest., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Introduction: High-risk human papillomavirus cervical infection is currently a well-established cause of cervical cancer. However, only a few women with persistent infections will develop cervical precancerous and malignant lesions. Approximately 20% of all cervical cancers are attributable to non-16/18 serotypes. This study aims to evaluate the results of our clinical approach to women with this infection., Material and Methods: We conducted an observational and prospective study from September 2012 to September 2017, which included women with isolated non-16/18 high-risk human papillomavirus infection (with normal cytology). After re-evaluation, two groups were compared: women with spontaneous regression of the infection and women with persistent infection. Clinical and demographic data were analysed as well as the rate of progression to precancerous and malignant lesions., Results: We included 165 women, of which 121 were re-evaluated with co-test at least one year later. After re-evaluation, 13.2% of women revealed precancerous lesions but only two (1.7%) of them presented high-grade squamous intraepithelial lesions. Sixty-seven women (55.4%) showed spontaneous regression of the infection and 54 women (44.6%) maintained it. Women with persistent infection developed more precancerous lesions (27.8%; p < 0.001) and high-grade squamous intraepithelial lesions (3.7%; p < 0.001). There was also an association between persistent infection and postmenopausal status., Discussion: Human papillomavirus 16/18 cervical infection is associated with higher risk of cervical cancer when compared with other serotypes., Conclusion: Re-evaluation with co-test one year after the diagnosis of isolated non-16/18 human papillomavirus infection seems to be a reasonable approach.

Introduction: The objectives of this study were to estimate the economic burden of HPV in Italy, accounting for total direct medical costs associated with nine major HPV-related diseases, and to provide a measure of the burden attributable to HPV 6, 11, 16, 18, 31, 33, 45, 52, 58 infections., Methods: A cost-of-illness incidence-based model was developed to estimate the incidences and costs of invasive cervical cancer, cervical dysplasia, cancer of the vulva, vagina, anus, penis, oropharyngeal, anogenital warts, and recurrent respiratory papillomatosis (RRP) in the context of the Italian National Health System (NHS). We used data from hospital discharge records (HDRs) of an Italian region and conducted a systematic literature review to estimate the lifetime cost per case, the number of incident cases, the prevalence of HPV9 types. Costs of therapeutic options not included in the diagnosis-related group (DRG) tariffs were estimated through a scenario analysis., Results: In 2018, the total annual direct costs were €542.7 million, with a range of €346.7-€782.0 million. These costs could increase considering innovative therapies for cancer treatment (range €16.2-€37.5 million). The fraction attributable to the HPV9 genotypes without innovative cancers treatment was €329.5 million, accounting for 61% of the total annual burden of HPV-related diseases in Italy. Of this amount, €135.9 million (41%) was related to men, accounting for 64% of the costs associated with non-cervical conditions., Conclusions: The infections by HPV9 strains and the economic burden of non-cervical HPV-related diseases in men were found to be the main drivers of direct costs.

Background: Despite being preventable, cervical cancer remains a major health concern among women. Persistent Human Papillomavirus (HPV) and other viral co-infections may influence cervical dysplasia. We determined and compared the prevalence and risk factors of cervical viral infections among the tribal and general population of southern coastal Karnataka, India., Methods: A population-based cross-sectional survey was conducted among 1140 and 1100 women from tribal and general population, respectively. Cervical infections with HPV, Epstein-Barr Virus (EBV), Cytomegalovirus (CMV) and Herpes-Simplex Virus (HSV) were examined using polymerase chain reactions (PCR) and DNA sequencing., Results: HPV prevalence was higher among tribal women (40.6%) than general population (14.3%) while the prevalence of EBV (55.1%) and CMV (49.4%) were lower among tribal women than general population (74.3% and 77.5%, respectively). HSV infection was observed in tribal women only (1.8%). Among HR-HPV strains, HPV-18 was predominant among tribal population (28.3%) while, HPV-16 was predominant among the general population (9.1%). Infections were associated with age, educational status, unemployment and personal hygiene of tribal women. Phylogenetic analysis revealed that HPV-16 variants of tribal participants were closely related to non-European sublineages indicating greater risk of HPV persistence and carcinogenesis., Conclusion: The study provides a comparative estimate for DNA virus infections of the cervix among women from general as well as tribal population in this region and also reveals a different type-specific pattern of viral infection. Further research is required to delineate the role of specific interactions between multiple virus infections and their role in carcinogenesis., Competing Interests: The authors have declared that no competing interests exist.

Background: Persistent high-risk human papillomavirus (HR-HPV) infection is the etiological cause of virtually all cervical cancer cases. HR-HPV screening achieved with earlier generations of HR-HPV tests has been instrumental in the prevention and early detection of cervical cancer worldwide. The first FDA-approved HR-HPV test, digene Hybrid Capture 2 HPV DNA Test (HC2), has been prominent in these efforts. Newer tests have since been developed to improve upon the capability of HC2 test., Methods: To evaluate the performance of a new multiplex real-time quantitative PCR assay for HR-HPV detection, CerviHPV HR-HPV Test (CerviHPV), 232 cervical swab specimens were collected and analyzed by HC2 and CerviHPV tests for comparison., Results: HC2 test detected 69 (29.7%) positive cases, whereas CerviHPV test reported 43 (18.5%) positive cases. The concordance rate between the two tests was 84.5% with a kappa value of 0.579. Additional analyses identified only HPV66 or low-risk HPV (LR-HPV) types in six HC2 positive discordant cases, suggesting these HC2 results to be false positive., Conclusion: CerviHPV test has two advantages over HC2 test: It contains a cellular control to eliminate false negative results due to failed sample collection and processing, and it can simultaneously detect and genotype the two most carcinogenic HPV types, HPV16 and 18. In this comparison study, CerviHPV test also demonstrated higher analytical specificity for HR-HPV genotypes than HC2 test. Therefore, CerviHPV test has the potential to become a viable option for cervical cancer screening in the clinics., (© 2018 Wiley Periodicals, Inc.)

Recent large-scale genomics studies of human papillomaviruses (HPVs) have shown a high level of genomic variability of HPV16, the most prevalent genotype in HPV-associated malignancies, and provided new insights into the biological and clinical relevance of its genetic variations in cervical cancer development. Here, we performed deep sequencing analyses of the viral genome to explore genetic variations of HPV16 that are prevalent in Japan. A total of 100 complete genome sequences of HPV16 were determined from cervical specimens collected from Japanese women with cervical intraepithelial neoplasia and invasive cervical cancer, or without cervical malignancies. Phylogenetic analyses revealed the variant distribution in the Japanese HPV16 isolates; overall, lineage A was the most prevalent (94.0%), in which sublineage A4 was dominant (52.0%), followed by sublineage A1 (21.0%). The relative risk of sublineage A4 for cervical cancer development was significantly higher compared to sublineages A1/A2/A3 (odds ratio = 6.72, 95% confidence interval = 1.78-28.9). Interestingly, a novel cluster of variants that branched from A1/A2/A3 was observed for the Japanese HPV16 isolates, indicating that unique HPV16 variants are prevalent among Japanese women.

Objectives: To evaluate the efficacy of a carrageenan-based lubricant gel in reducing the risk of genital human papillomavirus (HPV) infections in women., Methods: We conducted a planned interim analysis of a randomized, double-blind, placebo-controlled, phase 2B trial. Women aged 18 years and older were randomly assigned (1:1) to a carrageenan-based gel or a placebo gel to be self-applied every other day for the first month and before and after each intercourse during follow-up. Assessments were performed at 0.5, 1, 3, 6, 9 and 12 months. The primary outcome was incidence of a new infection by an HPV type that was not present at baseline. Intention-to-treat analyses were performed., Results: Between January 2013 and June 2017, a total of 280 participants were randomly assigned to the carrageenan (n = 141) or the placebo (n = 139) arm. All participants were included in safety analyses, but three (1%) were excluded from efficacy analyses (HPV results unavailable for two participants in the carrageenan and one participant in the placebo arm). The median follow-up time was 9.2 months (interquartile range, 1.9-13.2 months). A total of 59 (42%) of 139 participants in the carrageenan arm and 78 (57%) of 138 participants in the placebo arm became infected by at least one new HPV type (hazard ratio = 0.64, 95% confidence interval = 0.45-0.89, p 0.009). A total of 62 (44%) of 141 participants in the carrageenan arm versus 43 (31%) of 139 participants in the placebo arm reported an adverse event (p 0.02), none of which was deemed related to the gels., Conclusions: Our trial's interim analysis suggests that using a carrageenan-based lubricant gel can reduce the risk of genital HPV infections in women., (Copyright © 2018 European Society of Clinical Microbiology and Infectious Diseases. All rights reserved.)

Background: Chlamydia trachomatis may coinfect with human papillomavirus (HPV) and complicate the cervical pathogenesis. This study aimed to evaluate the prevalence, risk factors, and clinical outcomes of HPV/C. trachomatis coinfection in women from Inner Mongolia, China., Methods: We performed a polymerase chain reaction (PCR)-based HPV/C. trachomatis screening and cervical samples were analyzed by thinprep cytologic test. Statistical analysis was used to assess the association between demographic factors and coinfection., Results: Among the 2345 women recruited, the prevalences of HPV, C. trachomatis, and HPV/C. trachomatis coinfection were 36.0%, 14.3%, and 4.8%, respectively. The rate of multiple HPV genotypes was higher in coinfected women. HPV66 was the most frequently identified genotype in coinfected participants. The HPV DNA load was significantly higher in HPV monoinfected cases. In contrast, the DNA load of C. trachomatis was significantly higher in the coinfection group. Risk factors, including single women (odds ratio [OR] = 6.0, 95% confidence interval [CI], 4.044-8.782) and women with multiple sex partners (OR = 1.9, 95% CI, 1.324-2.824), were associated with coinfection. Importantly, coinfection was associated with increased risk for high-grade squamous intraepithelial lesions., Conclusions: HPV and C. trachomatis coinfection is an important risk factor for the progression of cervical lesions.

Objectives: Few studies on human papillomavirus (HPV) have been conducted in Mongolia. This study was performed to evaluate the prevalent HPV genotypes and their associations with cytology and demographic and behavioral characteristics in Mongolian women with cervical abnormalities., Methods: Exfoliated cell samples of 100 women who had a previous history of cervical abnormality were collected. Cytological interpretation was conducted microscopically and HPV genotyping was performed using the Roche Linear Array test. Study questionnaires were completed., Results: Overall, 25 HPV genotypes were detected in 47% of participants, and the most prevalent were HPV 16, 52, 58, and 33. Cytological examination revealed 12% of participants had atypical squamous cells of undetermined significance (ASC-US), 8% had low-grade squamous intraepithelial lesions (LSIL), 7% had high-grade squamous intraepithelial lesions (HSIL), and 14% had squamous cell carcinoma (SCC), while 59% of women had a normal cytology. HPV 16 was the most common type among women with a normal cytology and cervical cancer. However, women with cervical abnormalities including LSIL and HSIL were predominantly infected with HPV 52. Moreover, women aged <35 years had a significantly higher risk of HPV infection than those in the other age groups (p<0.05)., Conclusions: The prevalent trend of HPV genotypes observed in this cohort differs from that reported previously in Mongolia. These data may contribute to developing an effective strategy for cervical cancer prevention in Mongolia., (Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Objectives: Human papilloma virus (HPV) has been implicated in several types of epithelial cancer. The role of HPV in breast carcinogenesis has been a matter of debate fueled by conflicting reports in recent years. The aim of this study is to identify the prevalence of breast and cervical HPV infection in cancer patients by using a modern microarray approach., Materials and Methods: In the present prospective study, 201 breast cancer patients were included. For each patient a detailed medical history was taken and during the operation, under sterile conditions, samples were collected, from the tumour, the healthy adjacent breast tissue and any positive sentinel lymph nodes. In addition, for each patient a cervical sample was also collected. All samples were analysed for DNA of 24 types of HPV using a microarray technique., Results: Despite the high sensitivity of the technique used, no HPV DNA was identified in any of the breast or lymph node samples. Our analysis showed that patients with HPV positive cervical samples (28 cases) were more likely to have tumors with positive progesterone receptors (p=0.041) and were also more likely to have two or three positive lymph nodes (p=0.002)., Conclusion: In the present study, a combination of careful sample collection and a very sensitive microarray approach showed no correlation between HPV and breast cancer. However some characteristics of the breast tumors were different among patients with HPV DNA in their cervical samples., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Background: Previously, we demonstrated similar human papillomavirus (HPV)16/18 vaccine efficacy estimates and stable HPV16/18 antibody levels four years postvaccination in a nonrandomized analysis of women who received a varying number of doses of the bivalent HPV16/18 vaccine. Here we extend data to seven years following initial vaccination., Methods: We evaluated HPV16/18-vaccinated women who received one (n = 134), two (n 0/1 = 193, n 0/6 = 79), or three doses (n = 2043) to a median of 6.9 years postvaccination. Cervical HPV DNA was measured with the SPF10- DEIA-LiPA PCR system; HPV16/18-specific antibody levels were measured using enzyme-linked immunosorbent assays (n = 486). Infection and immunological measures were compared across vaccine dose groups. Prevalent HPV infection at year 7 was also compared with an unvaccinated control group (UCG). All statistical tests were two-sided., Results: Among women in the three-dose, two-dose 0/6 , two-dose 0/1 , and one-dose groups, cumulative incident HPV16/18 infection rates (No. of events/No. of individuals) were 4.3% (88/2036, 95% confidence interval [CI] = 3.5% to 5.3%), 3.8% (3/78, 95% CI = 1.0% to 10.1%), 3.6% (7/192, 95% CI = 1.6% to 7.1%), and 1.5% (2/133, 95% CI = 0.3% to 4.9%; P = 1.00, .85, .17 comparing the two-dose 0/6 , two-dose 0/1 , and one-dose groups to the three-dose group, respectively). The prevalence of other carcinogenic and noncarcinogenic HPV types, excluding HPV16/18/31/33/45, were high and not statistically different among all dose groups, indicating that the low incidence of HPV16/18 in the one- and two-dose groups was not due to lack of exposure. At seven years, 100% of participants in all dose groups remained HPV16 and HPV18 seropositive. A non-statistically significant decrease in the geometric mean of the HPV16 antibody levels between years 4 and 7 was observed among women in the three-dose group: -10.8% (95% CI = -25.3% to 6.6%); two-dose (0/6 months) group: -17.3% (95% CI = -39.3% to 12.8%), two-dose (0/1 month) group: -6.9% (95% CI = -22.1% to 11.2%), and one-dose group: -5.5% (95% CI = -29.7% to 27.0%); results were similar for HPV18., Conclusions: At an average of seven years of follow-up, we observed similar low rates of HPV16/18 infections and slight, if any, decreases in HPV16/18 antibody levels by dose group., (Published by Oxford University Press 2017. This work is written by US Government employees and is in the public domain in the US.)

Background: Some sexually transmitted infectious agents, such as Chlamydia trachomatis and Herpes simplex, cause local inflammation, and could contribute to Human Papillomavirus (HPV) and cervical lesion progression. Thus, the aim of this study was to determine any association between the presence of microorganisms of gynecological importance, sexual behavior, clinical and demographical variables to the development and progress of cervical lesions., Methods: One hundred and thirty-two women between 14 and 78 years and living at Vitória da Conquista, Bahia, Brazil, were included (62 individuals with cervical lesions and 70 without lesions). They answered a questionnaire to provide data for a socioeconomic and sexual activity profile. Samples of cervical swabs were collected and analyzed by PCR to detect genital microorganisms and HPV. Quantitative PCR was used to detect and quantify Ureaplasma urealyticum and Ureaplasma parvum. Univariate and multiple logistic regression were performed to measure the association with the cervical lesions, and an odds ratio (OR) with 95% confidence intervals (95%CI) were calculated. The Mann-Whitney U test was also used to compare the microorganism load in the case and control groups. The significance level was 5% in all hypotheses tested., Results: Cervical lesions were associated with: women in a stable sexual relationship (OR = 14.21, 95%CI = 3.67-55.018), positive PCR for HPV (OR = 16.81, 95%CI = 4.19-67.42), Trichomonas vaginalis (OR = 8.566, 95%CI = 2.04-35.94) and Gardnerella vaginalis (OR = 6.13, 95%CI = 1.53-24.61), adjusted by age and qPCR for U. parvum. U. parvum load showed a statistical difference between the case and control groups (p-value = 0.002)., Conclusion: Variables such as stable relationship, HPV, T. vaginalis, G. vaginalis were associated with cervical lesions in epidemiological studies. U. parvum load was higher in woman with cervical lesions compared with women without lesions. Additional studies are needed to better understand the role of these factors in cervical lesion development.

Objective: Estimate the prevalence of cervical HPV infection among women assisted by the Family Health Strategy and identify the factors related to the infection., Methods: A cross-sectional study involving 2,076 women aged 20-59 years old residing in Juiz de Fora, State of Minas Gerais, who were asked to participate in an organized screening carried out in units were the Family Health Strategy had been implemented. Participants answered the standardized questionnaire and underwent a conventional cervical cytology test and HPV test for high oncogenic risk. Estimates of HPV infection prevalence were calculated according to selected characteristics referenced in the literature and related to socioeconomic status, reproductive health and lifestyle., Results: The overall prevalence of HPV infection was 12.6% (95%CI 11.16-14.05). The prevalence for the pooled primer contained 12 oncogenic HPV types (31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66, and 68) was 8.6% (95%CI 7.3-9.77). In the multivariate analysis, it was observed that the following variables were significantly associated with a higher prevalence of HPV infection: marital status (single: adjusted PR = 1.40, 95%CI 1.07-1.8), alcohol consumption (any lifetime frequency: adjusted PR = 1.44, 95%CI 1.11-1.86) and number of lifetime sexual partners (≥ 3: adjusted PR = 1.35, 95%CI 1.04-1.74)., Conclusions: The prevalence of HPV infection in the study population ranges from average to particularly high among young women. The prevalence of HPV16 and HPV18 infection is similar to the worldwide prevalence. Homogeneous distribution among the pooled primer types would precede the isolated infection by HPV18 in magnitude, which may be a difference greater than the one observed. The identification of high-risk oncogenic HPV prevalence may help identify women at higher risk of developing preneoplastic lesions.

The classification of human papillomavirus (HPV) intratypic lineages by complete genome sequencing is a determinant in understanding biological differences in association with this disease. In this work, we have characterised complete HPV genomes from southern Brazil. Fifteen cervicovaginal Pap smear negative samples previously categorised as HPV-positive were sequenced using ultradeep sequencing, and 18 complete genomes from 13 different HPV types were assembled. Phylogenetic and genetic distance analyses were performed to classify the HPV genomes into lineages and sublineages. This is the first report describing the distribution of HPV intratype lineages of high and low oncogenic risk in asymptomatic women from southern Brazil.

Papillomavirus infection is one of the most common sexually transmitted infections. The aim of the study was to study the etiologic significance of the papillomavirus infection in the development of background diseases of the cervix and neoplasia. Under observation were 62 patients aged 18 to 55 years infected with human papillomavirus. All patients underwent complex clinical and anamnestic, laboratory and instrumental examination. Also, a review and advanced colposcopy was performed. As a result of the study, 53 (85.4%) women under observation were found to have various pathologies of the cervix. Dysplasia of mild degree (CIN 1 degree) was found in 12 (57.1%), moderate dysplasia (CIN 2 degree) - in 9 (42.9%) women. With further examination, it was found that patients along with dysplasia of varying severity had concomitant pathology of the cervix uteri. Cervical dysplasia was most often diagnosed in combination with another pathology of the cervix, which accounted for 85.7% of cases. It has been established that squamous epithelial lesion of the cervix is most often a consequence of late diagnosis and an untreated background process. At the same time, modern diagnostics requires a whole range of diagnostic measures to establish a diagnosis in the early stages of development and conduct differential diagnosis of a benign or malignant process.

Background: Methylation of the human papillomavirus (HPV) DNA has been proposed as a novel biomarker. Here, we correlated the mean methylation level of 12 CpG sites within the L1 gene, to the histological grade of cervical precancer and cancer. We assessed whether HPV L1 gene methylation can predict the presence of high-grade disease at histology in women testing positive for HPV16 genotype., Methods: Pyrosequencing was used for DNA methylation quantification and 145 women were recruited., Results: We found that the L1 HPV16 mean methylation (±SD) significantly increased with disease severity (cervical intraepithelial neoplasia [CIN] 3, 17.9% [±7.2] vs CIN2, 11.6% [±6.5], P < .001 or vs CIN1, 9.0% [±3.5], P < .001). Mean methylation was a good predictor of CIN3+ cases; the area under the curve was higher for sites 5611 in the prediction of CIN2+ and higher for position 7145 for CIN3+. The evaluation of different methylation thresholds for the prediction of CIN3+ showed that the optimal balance of sensitivity and specificity (75.7% and 77.5%, respectively) and positive and negative predictive values (74.7% and 78.5%, respectively) was achieved for a methylation of 14.0% with overall accuracy of 76.7%., Conclusions: Elevated methylation level is associated with increased disease severity and has good ability to discriminate HPV16-positive women that have high-grade disease or worse., (© The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Human papillomavirus (HPV) has been found in several regions of the body, including the oral cavity. Recently, this virus has been associated with oropharyngeal cancer, but little is known about HPV transmission to the oral cavity. We carried out a study to investigate concurrent oral and cervical infections in 76 asymptomatic women attending a healthcare program. Demographic and behavior data were obtained through a structured questionnaire. Oral and cervical mucosa scrapings were collected and stored for DNA extraction. HPV DNA amplification was performed by polymerase chain reaction assay (PCR) using both primers My09/My11 and FAP59/64, followed by HPV typing with restriction fragment length polymorphism analysis (RFLP) and sequencing. The data collected revealed no risk factors for HPV infection in these 76 women. HPV prevalence of 9.2 and 5.3% was found in cervical and oral mucosa, respectively. Concurrent infections by discordant types were detected in one case only. Sequencing procedures allowed us to detect a new putative HPV 17 subtype from the Betapapillomavirus genus. Our results support the view that cervical and oral HPV infections are independent events. The observed low prevalence of both oral and cervical HPV infections could be associated with attendance in a healthcare program., (Copyright © 2016 Sociedade Brasileira de Infectologia. Published by Elsevier Editora Ltda. All rights reserved.)

Objectives: Anal human papillomavirus (HPV) is highly prevalent in men who have sex with men (MSM) of all ages, whereas cervical HPV declines with age. We explore the hypothesis that different sexual behavioural patterns are the basis of this difference in age distribution., Methods: Published data on age-specific HPV prevalence for women (cervical HPV) were extracted from a large meta-analysis and for MSM (anal HPV) from the EXPLORE study of HIV-negative MSM. Age-specific data on recent sexual activity were extracted from two behavioural surveys: the second Australian Study of Health and Relationships survey and the 2013 Gay Community Periodic Survey., Results: At least 50% of MSM at all ages reported more than one sexual partner in the past 6 months. In comparison, 33% of women aged 16-19 years reported more than one partner over the past year. This decreased to 19% and 6% in women aged 20-29 and 30-39 years, respectively, and to fewer than 5% of women in older age groups. Prevalent anal HPV was detected in over 50% of MSM in each age group. Prevalence did not decline with age. In contrast, there was a steady decrease in cervical HPV prevalence with age. Cervical HPV prevalence fell from 23% among North American women aged <25 years to 3% in women aged ≥65 years., Conclusions: In contrast to the decreasing prevalence with age among heterosexual women, the high prevalence and lack of decline in prevalent anal HPV among older MSM are likely to be related to continuing high rates of newly acquired HPV infection from ongoing sexual exposure through new partners., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/)

Polymorphisms in chemokine receptors play an important role in the progression of cervical intraepithelial neoplasia (CIN) to cervical cancer (CC). Our study examined the association of CCR2-64I (rs1799864) andCCR5-Δ32 (rs333) polymorphisms with susceptibility to develop cervical lesion (CIN and CC) in a Brazilian population. The genotyping of 139 women with cervical lesions and 151 women without cervical lesions for the CCR2-64I and CCR5-Δ32 polymorphisms were performed using polymerase chain reaction-restriction fragment length polymorphism. The individuals carrying heterozygous or homozygous genotypes (GA+AA) for CCR2-64I polymorphisms seem to be at lower risk for cervical lesion [odds ratio (OR) = 0.37, p = 0.0008)]. The same was observed for the A allele (OR = 0.39, p = 0.0002), while no association was detected (p > 0.05) with CCR5-Δ32 polymorphism. Regarding the human papillomavirus (HPV) type, patients carrying the CCR2-64Ipolymorphism were protected against infection by HPV type 16 (OR = 0.35, p = 0.0184). In summary, our study showed a protective effect ofCCR2-64I rs1799864 polymorphism against the development of cervical lesions (CIN and CC) and in the susceptibility of HPV 16 infection.

Few studies have been conducted on the relationship between metabolic syndrome (MetS) and cervical human papillomavirus (HPV) incidence and persistent infection. We performed a prospective cohort study including 8598 female employees in Hunan, China. First, the subjects were stratified into HPV-negative (N = 7282) and HPV-positive (N = 1316) subgroups, according to the results of an HPV DNA test at baseline. Second, comparisons of the risks of HPV incident and persistent infection between MetS-positive (exposed) and MetS-negative (unexposed) groups were conducted among the HPV-negative and -positive subgroups, respectively. There were 976 (11.39%) subjects diagnosed with MetS and 1316 subjects diagnosed with HPV infection at baseline. The 12-month cumulative incidence of any type of HPV and high-risk type HPV were 7.28% (530/7282) and 6.26% (456/7282), respectively. Obesity was a modifier of the association between MetS and HPV incident infection. As long as obesity presented, MetS and hypertriglyceridemia were significantly associated with an increased risk of HPV incident infection (any-type or high-risk type) (adjusted risk ratios (RR) were 2.88 (95% confidence interval (CI): 1.16, 7.19) and 3.29 (95% CI: 1.47, 7.38), respectively). Among those infected with HPV at baseline, the 12-month type-specific persistence rates were 51.67% and 53.38% for any-type and high-risk type HPV, respectively. No interaction was found between obesity and MetS with regard to the risk of HPV persistence. After adjustment for confounding factors, MetS was still associated with increased risk of any-type HPV persistence (RRadj = 1.21, 95% CI: 1.05, 1.41) and high-risk type HPV persistence (RRadj = 1.25, 95% CI: 1.09, 1.46). No single metabolic component was associated with the risk of HPV persistence. The prevalence of MetS was 11.39% among the Hunan female occupational population. MetS was associated with an increased risk of persistent cervical HPV infection and also with an increased risk of HPV incident infection when obesity presented as well.

Cervical cancer is caused by infection with high risk human papillomavirus (HR-HPV). Inducible nitric oxide synthase (iNOS), a soluble factor involved in chronic inflammation, may modulate cervical cancer risk among HPV infected women. The aim of the study was to measure and correlate plasma nitrite/nitrate levels with tissue specific expression of iNOS mRNA among women with different grades of cervical lesions and cervical cancer. Tissue biopsy and plasma specimens were collected from 120 women with cervical neoplasia or cancer (ASCUS, LSIL, HSIL and invasive cancer) and 35 women without cervical abnormalities. Inducible nitric oxide synthase (iNOS) mRNA from biopsy and plasma nitrite/nitrate levels of the same study subjects were measured. Single nucleotide polymorphism (SNP) analysis was performed on the promoter region and Ser608Leu (rs2297518) in exon 16 of the iNOS gene. Differences in iNOS gene expression and plasma nitrite/nitrate levels were compared across disease stage using linear and logistic regression analysis. Compared to normal controls, women diagnosed with HSIL or invasive cancer had a significantly higher concentration of plasma nitrite/nitrate and a higher median fold-change in iNOS mRNA gene expression. Genotyping of the promoter region showed three different variations: A pentanucleotide repeat (CCTTT) n, -1026T > G (rs2779249) and a novel variant -1153T > A. These variants were associated with increased levels of plasma nitrite/nitrate across all disease stages. The higher expression of iNOS mRNA and plasma nitrite/nitrate among women with pre-cancerous lesions suggests a role for nitric oxide in the natural history of cervical cancer., (Copyright © 2015. Published by Elsevier Inc.)

Background: HPV infects multiple sites in the epithelium, including the genitals and oral cavity. The relation between genital and oral infections and serum antibodies can help explain the natural history and epidemiology of HPV., Methods: We analyzed HPV data from NHANES derived from self-collected vaginal swabs (women ages 14-59, 2003-12), oral rinses (men and women 14-69, 2009-12), and serum (men and women 14-59, 2003-10)., Results: Type-concordance of cervicogenital and oral infections in women was found to vary widely by age. Prevalence of oral infections with type-concordant antibodies was low but varied by sex: 0.2 % (95 % CI 0.0-0.8) for women vs 0.8 % (95 % CI 0.4-1.3) for men. Vaccination was associated with a reduced risk of cervicogenital infection for vaccine genotypes among ages 14-17 (0.2 (95 % CI 0.1-0.8)) and 18-24 (0.2 (95 % CI 0.1-0.3). Seroprevalence trends in women showed a dramatic increase for recent birth cohorts, likely due to vaccination. By contrast, trends for men remained relatively constant. Age-specific cervicogenital prevalence showed a consistent peak in the late teens and twenties. Relative cervicogenital prevalence has largely been decreasing since the 1940-50 birth cohort., Conclusions: There are complex patterns in HPV prevalence trends and type-concordance across infection sites and serum antibodies. A multisite sampling scheme is needed to better understand the epidemiology and natural history of HPV.

Objective: To investigate the distribution of HPV subtypes and analyze variation in infection trends during a 6-year period in Sichuan Province, China., Methods: A cross-sectional observational study was conducted at a center in Chengdu between January 1, 2009, and December 31, 2014. Patients with at least one type of cervical disease confirmed by histology and cytology were eligible for inclusion. Cervical specimens were tested for the presence of high-risk and low-risk HPV subtypes by reverse membrane hybridization., Results: Among 10 682 participants, 3370 women (31.5%) were infected with HPV. The most frequently detected high-risk genotypes were HPV16 (n=791; 27.1%), HPV58 (n=476; 16.3%), HPV33 (n=273; 9.4%), HPV52 (n=244; 8.4%), and HPV18 (n=201; 6.9%). The most frequently detected low-risk genotype was HPV6 (n=703; 40.8%). The detection rates of HPV33 (from 7.9% to 10.2%) and HPV58 (from 14.0% to 16.7%) increased over the 6-year period, whereas those of HPV16 (from 32.3% to 24.9%) and HPV18 (from 10.0% to 6.2%) decreased. The prevalence of HPV infection was highest among women aged 21-25 years (χ(2)=191.189; P<0.001)., Conclusion: HPV58 and HPV33 were the most prevalent subtypes in Sichuan. Changes in the prevalences of infection with different HPV subtypes have been identified., (Copyright © 2015 International Federation of Gynecology and Obstetrics. Published by Elsevier Ireland Ltd. All rights reserved.)

Our objective was to evaluate whether vitamin D deficiency is associated with cervical human papilloma virus (HPV) infection in women with SLE. This is a cross-sectional study of 67 women with SLE. A structured questionnaire was administered to ascertain the possible risk factors associated with cervical HPV infection. A gynaecological evaluation and cervical cytology screening were made. HPV detection and genotyping was made by PCR and linear array assay. Serum 25 hydroxyvitamin D levels were quantified by chemiluminescence immunoassay. Mean age and disease duration were 44.8 ± 10.6 and 42.5 ± 11.8 years, respectively. Demographic characteristics were similar in patients with and without deficiency (<20 ng/ml and ≥20 ng/ml). There were 28.4% of women with cervical HPV infection and 68.4% had high-risk HPV infections. Patients with 25 hydroxyvitamin D levels <20 ng/ml had a higher prevalence of cervical HPV infection than those with levels ≥20 ng/ml (30.7% vs. 25.8%; p = 0.72). We found no significant difference when high-risk HPV infection was evaluated (36.8% vs. 31.5%; p = 0.73). In conclusion, women with SLE have a high prevalence of vitamin D deficiency and cervical HPV infection. However, we found no association between vitamin D deficiency and cervical HPV., (© The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.)

During 2009-2011, we reported that the oral and cervical prevalence of human papillomavirus (HPV) was high by international standards at 9.3% and 74%, respectively, in youth aged 15-23 years attending a youth clinic in Stockholm. After gradual introduction of public HPV vaccination during 2007-2012, between 2013 and 2014, when 73% of the women were HPV-vaccinated, but not necessarily before their sexual debut, oral HPV prevalence had dropped to 1.4% as compared with 9.3% in 2009-2011 (p < 0.00001). Cervical HPV prevalence was high and common cervical high-risk types were HPV51, 56, 59, 73, 16, 39, 52, and 53. However, it was shown that HPV16, 31, and 70 were significantly less common among HPV-vaccinated women than among those who had not received the vaccine.

High risk (oncogenic) human papillomavirus (HPV) infection causes cervical cancer. Infections are common but most clear naturally. Persistent infection can progress to cancer. Pre-neoplastic disease (cervical intraepithelial neoplasia/CIN) is classified by histology (CIN1-3) according to severity. Cervical abnormalities are screened for by cytology and/or detection of high risk HPV but both methods are imperfect for prediction of which women need treatment. There is a need to understand the host virus interactions that lead to different disease outcomes and to develop biomarker tests for accurate triage of infected women. As cancer is increasingly presumed to develop from proliferative, tumour initiating, cancer stem cells (CSCs), and as other oncogenic viruses induce stem cell associated gene expression, we evaluated whether presence of mRNA (detected by qRT-PCR) or proteins (detected by flow cytometry and antibody based proteomic microarray) from stem cell associated genes and/or increased cell proliferation (detected by flow cytometry) could be detected in well-characterised, routinely collected cervical samples from high risk HPV+ve women. Both cytology and histology results were available for most samples with moderate to high grade abnormality. We found that stem cell associated proteins including human chorionic gonadotropin, the oncogene TP63 and the transcription factor SOX2 were upregulated in samples from women with CIN3 and that the stem cell related, cell surface, protein podocalyxin was detectable on cells in samples from a subset of women with CIN3. SOX2, TP63 and human gonadotrophin mRNAs were upregulated in high grade disease. Immunohistochemistry showed that SOX2 and TP63 proteins clearly delineated tumour cells in invasive squamous cervical cancer. Samples from women with CIN3 showed increased proliferating cells. We believe that these markers may be of use to develop triage tests for women with high grade cervical abnormality to distinguish those who may progress to cancer from those who may be treated more conservatively.

The development of efficacious prophylactic human papillomavirus vaccines provided an opportunity for the primary prevention of related infections and diseases. Certain oncogenic human papillomaviruses that preferentially infect the genital epithelium cause cervical cancer and a substantial proportion of anal, penile, vaginal, vulvar and oropharyngeal cancers. Following extensive clinical trials demonstrating their efficacy and safety, two vaccines have been in global use for over 6 years. This review summarises the accumulated evidence regarding their high level of efficacy, safety in population usage, reductions in genital warts, infections and cervical disease following their adoption, and facilitators and barriers to achieving high vaccination coverage. The review also discusses practical issues and frequently asked questions regarding duration of effect, vaccination of women treated for cervical disease and alternate vaccination schedules, as well as the need to review cervical screening strategies in the post- vaccination environment., (© 2014 The Author. Journal of Paediatrics and Child Health © 2014 Paediatrics and Child Health Division (Royal Australasian College of Physicians).)

We examined the concurrence of multiple human papillomavirus (HPV) infections in 47,617 women who underwent cervical screening in New Mexico between December 2007 and April 2009 using the LINEAR ARRAY HPV Genotyping Test (Roche Diagnostics, Indianapolis, Indiana), which detects 37 different types of HPV. Our primary goal was to examine the distributions of multiple HPV types with a special interest in negative interactions, which could signal the possibility of type replacement associated with a common niche if some HPV types were prevented by vaccination. Multiple infections were found to be more common than expected under independence, but this could largely be accounted for by a woman-specific latent heterogeneity parameter which was found to be dependent on age and cytological grade. While multiple infections were more common in young women and in those with abnormal cytology, greater heterogeneity was seen in older women and in those with normal cytology, possibly reflecting greater variability in exposure due to current or past HPV exposure or due to heterogeneity in related HPV reactivation or in immune responses to HPV infection or persistence. A negative interaction was found between HPV 16 and several other HPV types for women with abnormal cytology but not for those with normal cytology, suggesting that type replacement in women vaccinated against HPV 16 is unlikely to be an issue for the general population., (© The Author 2014. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objective: We evaluated time to clearance of high risk (HR) HPV infection in relation to functional variants in three genes (CYP1A1, GSTT1, and GSTM1)., Methods: The study group consisted of 450 HR-HPV infected women from the Atypical squamous cells of undetermined significance-low-grade squamous intraepithelial Lesion Triage Study (ALTS) cohort followed up at the clinical center at Birmingham, Alabama. The Cox proportional hazard model with the Wei-Lin-Weisfeld (WLW) approach was used, controlling for relevant covariates., Results: Women who were polymorphic for CYP1A1 experienced an HR-HPV clearance rate that was 20% (HR=0.80, p=0.04) lower than women without the polymorphism for CYP1A1, adjusting for all other cofactors. The GSTM1 null genotype was associated with higher HR-HPV clearance rate (HR=1.39, p=0.006). The polymorphism in GSTT1 was not significantly associated with time to clearance of HR-HPV., Conclusions: Xenobiotic metabolism genes may influence the natural history of HR-HPV infection and its progression to cervical cancer., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Persistence of high-risk (HR-) human papillomavirus (HPV) infection of the uterine cervix increases the risk of cervical cancer. Oral HPV infections are among potential covariates of long-term genotype-specific persistent cervical HR-HPV infections. It is not known whether this persistence reflects inability of the host to reject HPV infections in general. A case-control setting was designed to estimate the covariates of long-term persistent cervical HR-HPV infections using multivariate generalized estimating equation (GEE) models. HPV was detected with PCR using GP05+/GP06+-primers and genotyped for 24 HPVs with a Multimetrix-kit. The cases (n=43) included women who had genotype-specific persistent cervical HR-HPV infection for at least 24 months (24M+) and controls were women who tested repeatedly HPV-negative in their cervical samples (n=52). These women represent a sub-cohort of the Finnish Family HPV Study. The cases differed significantly from the HPV-negative controls in several aspects: they were younger, had a longer mean time to incident oral HPV infection (40.7 versus 23.6 months), longer duration of oral HPV persistence (38.4 versus 14.1 months), and longer time to clearance of their oral HPV infection (50.0 versus 28.2 months). In multivariate GEE analysis, the second pregnancy during the follow up was the only independent predictor with significant protective effect against 24M+ persistent cervical HR-HPV infections, OR of 0.15 (95% CI 0.07-0.34). To conclude, long-term persistent cervical HR-HPV infections are associated with a prolonged clearance of oral HR-HPV infections while new pregnancy protects against persistent cervical HR-HPV infections., (© 2014 The Authors Clinical Microbiology and Infection © 2014 European Society of Clinical Microbiology and Infectious Diseases.)

Objective: To describe the distribution of specific types of low-risk (LR) human papillomavirus (HPV) among a general population of northern Chinese women., Methods: Between 2007 and 2012, 118 096 women were tested with the HPV Geno-Array Test Kit (HybriBio) at China Medical University's Shengjing Affiliated Hospital, Shenyang, China. Among these women, 80 418 underwent cervical cytology and colposcopic examination, and 30 961 of these had a cervical biopsy. The prevalence of HPV infection among the women was analyzed according to age, and cytologic and histologic findings., Results: CP8304 was the most common type of LR-HPV overall, and was most prevalent in the youngest age group. The overall prevalence of LR-HPV (averaged across all types) was 1.7% in women with normal cytology, 8.8% in those with atypical squamous cells of undetermined significance (ASCUS), 8.0% in those with low-grade squamous intraepithelial lesions (LSIL), and 5.8% in those with high-grade squamous intraepithelial lesions (HSIL). LR-HPV alone, without any high-risk (HR)-HPV, was most common among women with ASCUS and cervical intraepithelial neoplasia (CIN) not otherwise specified (CINNOS) together. Co-infections of LR-HPV and HR-HPV were most common among women with LSIL and CIN1., Conclusion: These data will facilitate modeling of the cost-effectiveness of a prophylactic LR-HPV vaccination in China., (Copyright © 2014 International Federation of Gynecology and Obstetrics. Published by Elsevier Ireland Ltd. All rights reserved.)

Data from the National Health and Nutrition Examination Survey, 2009-2010, indicated that the prevalence of human papillomavirus (HPV) infection among women was 42.7% in the cervix and 3.8% in the oral cavity. The prevalence of oral HPV infection was 5-fold higher among women with than among those without cervical HPV infection (7.0% vs 1.4%; prevalence ratio, 4.9 [95% confidence interval, 2.7-8.7]). Among the 3% of women with HPV detected at both sites, complete type concordance was detected in 6.6%, and partial agreement was detected in 37.7%. These data suggest that HPV infections at these 2 sites are not independent, although type-specific concordance is low.

Background: Anal cancer is more common in women than in men, yet little is known about the natural history of human papillomavirus (HPV) in women. The objective was to examine the natural history of anal HPV in heterosexual women., Methods: Young women participating in an HPV cohort study were seen at 4-month intervals for cervical and anal HPV testing. Time to clearance was estimated using the Kaplan-Meier approach; risks for persistence were assessed using Cox regression models., Results: Seventy-five women (mean age, 23.5 ± 4.1 years) who tested positive for anal HPV were followed for a mean of 84.5 ± 44.9 months. By 3 years, 82.5% of anal non-16 high-risk (HR) HPV, 82.6% of low-risk (LR) HPV, and 76.2% of HPV-16 infections had cleared. By 3 years, only 36.4% of women had become negative for all HPV types. In the multivariable model, concurrent cervical HPV-16 (P < .001), weekly alcohol use (P = .015), anal touching during sex (P = .045), recent anal sex (P = .04), and no condom use during anal sex (P = .04) were associated with HPV-16 persistence. Greater number of new sex partners (P = .024) and condom use during vaginal sex (P = .003) were associated with clearance. Similar associations were found for clearance in all HR-HPV infections. Only concomitant cervical HPV was associated with non-16 HR-HPV persistence., Conclusions: The majority of anal HPV infections cleared within 3 years. HPV-16 infections were slower to clear than other HR-HPV infections, consistent with its role in anal cancer. Specific sexual behaviors were associated with persistence, suggesting that education and behavioral interventions may decrease persistence.

Objective: Cervical cancer is one of the most common malignancies worldwide, yet it is preventable by population screening. In a previous study, we confirmed the feasibility of utilizing whole slide imaging (WSI) of cell block (CB) preparations to overcome the limitations of digitizing cytologic samples. In this study, we evaluated the accuracy of WSI in identifying various organisms and nonneoplastic findings., Study Design: A total of 335 WS images from Pap CB preparations were analyzed using the Aperio system. The test performance characteristics of ThinPrep (TP) and WSI samples were compared for adequacy, for the presence of bacterial vaginosis (BV), fungi, Trichomonas vaginalis (TV) and herpes simplex virus (HSV) and for nonneoplastic findings., Results: The WSI samples contained optimal material from all preparations. BV was diagnosed in 33 WSI versus 36 TP samples. Budding yeasts and/or pseudohyphal forms were noted in 18 WSI versus 19 TP samples. TV organisms (10 of 11 samples) and 1 HSV case were accurately identified in the WSI and TP samples. Squamous metaplasia, keratosis and reactive/reparative and inflammatory changes were easily identified by WSI., Conclusions: The concept of WSI from Pap CB preparations is potentially feasible for adoption. Digital remote web-based technology eliminates the need for an individual on site, saving time and resources., (© 2014 S. Karger AG, Basel.)

Objective: To identify the prevalence and factors associated with cervical human papillomavirus infection in women with systemic lupus erythematosus, Methods: This cross-sectional study collected traditional and systemic lupus erythematosus-related disease risk factors, including conventional and biologic therapies. A gynecological evaluation and cervical cytology screen were performed. Human papillomavirus detection and genotyping were undertaken by PCR and linear array assay., Results: A total of 148 patients were included, with a mean age and disease duration of 42.5±11.8 years and 9.7±5.3 years, respectively. The prevalence of squamous intraepithelial lesions was 6.8%. The prevalence of human papillomavirus infection was 29%, with human papillomavirus subtype 59 being the most frequent. Patients with human papillomavirus were younger than those without the infection (38.2±11.2 vs. 44.2±11.5 years, respectively; p = 0.05), and patients with the virus had higher daily prednisone doses (12.8±6.8 vs. 9.7±6.7 mg, respectively; p = 0.01) and cumulative glucocorticoid doses (14.2±9.8 vs. 9.7±7.3 g, respectively; p = 0.005) compared with patients without. Patients with human papillomavirus infection more frequently received rituximab than those without (20.9% vs. 8.5%, respectively; p = 0.03). In the multivariate analysis, only the cumulative glucocorticoid dose was associated with human papillomavirus infection., Conclusions: The cumulative glucocorticoid dose may increase the risk of human papillomavirus infection. Although rituximab administration was more frequent in patients with human papillomavirus infection, no association was found. Screening for human papillomavirus infection is recommended in women with systemic lupus erythematosus.

External genital warts (EGWs) are a common sexually transmitted infection caused by the human papillomavirus (HPV). Although over 100 HPV types have been identified, some of which are associated with cancer, EGWs are caused by noncancerous HPV subtypes 6 and 11. This cutaneous manifestation of HPV infection can be asymptomatic or produce warty lesions that may assume a cauliflower-like, flat, papular, or keratotic appearance. Physical symptoms may also accompany warts, such as pruritus, burning, pain, and obstruction. EGWs typically appear in anogenital areas, such as the vulva, penis, groin, perineum, perianal skin, or mucosal surfaces. EGWs are typically a transient type of infection that often spontaneously regresses without treatment, but long-term remission rates are currently unknown. Treatment is determined according to the size and number of lesions, which can cluster or develop at multiple sites. Because of the individual variability in disease, treatment should be determined on a case-by-case basis. Further investigation, such as a biopsy, may be advisable in cases of atypical lesions, lesions that are unresponsive to therapies, and immunocompromised individuals, who are essentially more susceptible to HPV infections and less responsive to treatment. Although HPV testing is available, it is not currently recommended for detection and HPV typing. Differential diagnoses may include normal skin variations, other infectious or inflammatory diseases, and cancerous growths.

Background: The epidemiology of infection with multiple human papillomavirus (HPV) types in female adolescents is poorly understood. The purpose of this study was to explore the epidemiology of infection with multiple HPV types in adolescents and its association with demographic, behavioral and biological variables, as well as with cytological abnormalities., Methods: This community-based study included 432 sexually active females between 15 and 19 years of age. Genotyping for 30 HPV types was performed using a reverse blot strip assay/restriction fragment length polymorphism. Unconditional multivariate logistic regression was performed to identify factors significantly associated with HPV infection. The association between HPV infection and cytological abnormalities was calculated using a prevalence ratio., Results: The most common HPV types detected were 16, 51, 31, 52 and 18. Of the 121 HPV-positive women, 54 (44.6%) were infected with multiple HPV types. Having more than one lifetime sexual partner was associated with infection with any HPV infection, single HPV infection, and infection with multiple HPV types. The presence of cytological abnormalities was associated with infection with multiple HPV types., Conclusions: Co-infecting HPV genotypes occur in a high proportion of sexually active adolescents. Socio-demographic or sexual behavior factors associated with single HPV infection were similar to those associated with multiple HPV types. The higher risk of cytological abnormalities conferred by infection with multiple HPV types suggests a potential role of co-infection in the natural history of HPV infection.

Objective: To investigate if HPV cervical infection is associated with spontaneous abortion in a Mexican population., Study Design: Case control study including 281 women from two Social Security Hospitals in Merida, Mexico. Cases were women with spontaneous abortion attending for curettage, and controls were pregnant women at term who attended for delivery. HPV molecular detection and typing of HPV 16, 18, 58 and 6/11 was performed on cervical samples, and TORCH serology IgM tests (against T. gondii, CMV, HSV) were performed on cases. Data were analyzed using Chi square, odds ratio and linear regression tests., Results: HPV global prevalence was 19.8% (24.4% in cases and 15.2% in controls). HPV types 16 and 58 were the most frequently detected in both groups. Multiple HPV types concurrent infection were found in 31.4% of typified samples. Amongst cases 27.3% of HPV positive women reported at least one previous pregnancy loss; compared to 17.43% amongst HPV negative women. Nevertheless, HPV was not significantly associated with spontaneous or to repetitive abortion. Cases were 60.2% positive to any TORCH agent, although it was not significantly associated to referred miscarriage history. Spontaneous abortion was associated to a previous pregnancy loss and to women's age older than 35 years old. HPV infection was significantly associated to alcohol intake before pregnancy and to multiple sexual partners., Conclusion: HPV cervical infection was not associated with spontaneous abortion. HPV in spontaneous abortion and other adverse pregnancy outcomes merits further study., (Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.)

Objective: To investigate the association of human papillomavirus (HPV) in the pubic hair follicles of males with HPV infection in their female sexual partners., Methods: We included in this study 21 female patients with HPV infection, including 8 cases of cervical cancer, 5 cases of atypical cervical hyperplasia, 5 cases of cervical condyloma, and 3 cases with unidentified causes. We also enlisted 52 men without visible condyloma acuminatum in the external genitalia as healthy controls. We detected HPV in the pubic hair follicles of the female patients' male sexual partners and the healthy male controls by PCR and reverse hybridization in situ., Results: HPV positive was found in 6 (28.6%) of the 21 women's male partners, in whom the HPV types were correspondent situ. to those of the female patients., Conclusion: HPV in the pubic hair follicles of men might be one of the causes of HPV-related cervical lesions in their female sexual partners.

Aim: To evaluate the prevalence of coexisting anal human papillomavirus (HPV) infection and concordance of HPV types in women with cervical HPV infection and to investigate the possible predictors for anal HPV infection., Methods: Study group was composed of women referred with documented cervical HPV infection. All patients had undergone anal HPV DNA testing., Results: One hundred and six patients presenting with cervical HPV infection were eligible for the study. Overall, 24 and 20 distinct HPV genotypes were detected from cervical and anal specimens, respectively. We observed a considerably high prevalence (51.9 %) of coexisting anal HPV infection in our study group. A majority of the women who were found to have anal HPV infection were infected with oncogenic or probable oncogenic types (64.6 %). There were 20.0 and 58.3 % rate of total and partial concordance between the two sites, respectively. We found that no demographic parameter but history of anal intercourse was related with the risk of anal HPV infection., Conclusion(s): Women with cervical HPV infection have a considerable risk for coexisting anal HPV infection. Concordance of HPV types infecting the cervix and anal canal is relatively high. There is no strong predictor for anal HPV infection in this population.

Preterm birth is the major cause of neonatal mortality and morbidity, and bacterial infections that ascend from the lower female reproductive tract are the most common route of uterine infection leading to preterm birth. The uterus and growing fetus are protected from ascending infection by the cervix, which controls and limits microbial access by the production of mucus, cytokines, and antimicrobial peptides. If this barrier is compromised, bacteria may enter the uterine cavity, leading to preterm birth. Using a mouse model, we demonstrate, to our knowledge for the first time, that viral infection of the cervix during pregnancy reduces the capacity of the female reproductive tract to prevent bacterial infection of the uterus. This is due to differences in susceptibility of the cervix to infection by virus during pregnancy and the associated changes in TLR and antimicrobial peptide expression and function. We suggest that preterm labor is a polymicrobial disease, which requires a multifactorial approach for its prevention and treatment.

Background: Information on genital wart incidence in adolescents and young adults before human papillomavirus (HPV) vaccination is important for understanding the impact of the vaccine on the epidemiology of this early outcome of HPV infection., Methods: The study population included 11- to 29-year-old enrollees of Northern California Kaiser Permanente between July 1, 2000, and July 1, 2005, before the availability of the HPV vaccine. We identified genital warts with an algorithm combining genital wart-specific International Classification of Diseases, Ninth Revision, Clinical Modification codes (078.10, 078.11, and 078.19) with physician-recorded anatomic locations. We calculated sex- and age-specific incidence rates of genital warts and described the specific anatomic location of presentation, as well as recurrences of genital warts., Results: We identified 1,682 cases of genital warts among 181,264 individuals. The incidence rate was highest among women (6.3/1000 person-years) and men (2.9/1000 person-years) aged 20 to 24 years old. Among women (n = 96,792), 63.4% of the 1240 incident genital wart cases occurred on the vulva and 21.1% on the cervix. Among men (n = 84,472), 91.6% of the 442 incident genital wart cases did not have a specific anatomic location recorded. Most people with an incident genital wart diagnosis (87.2%) did not have a recurrence during the observation period., Conclusions: Our study found that the incidence of genital warts was highest among persons aged 20 to 24 years using a unique method to identify the location of the wart. Information on incidence of genital warts before vaccine use provides baseline data that can be used to measure HPV vaccine impact.

Genital human papillomavirus (HPV) infection is the most common sexually transmitted infection. Most HPV infections are benign and resolve on their own, but some women develop persistent HPV infections. Persistent HPV infection with certain high-risk HPV genotypes is the necessary cause of most epithelial lesions of the uterine cervix. The importance of latent or quiescent HPV, waning immunity, hormonal milieu, microbiota, and other factors modifying the natural history of HPV infections across a woman's lifetime deserves further study. Promising biomarkers are emerging that may aid in defining which HPV-infected women are at risk of developing invasive cervical cancer., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Background: The Expanded Program on Immunization currently considers offering Human Papilomavirus vaccine on a routine basis in Vietnam. However, as the current available vaccine can prevent only two types HPV 16 and 18, before implementing a large-scale vaccine campaign we need information about the prevalence of infection with only HPV 16 and 18 in Viet Nam. This study was done in 5 large cities in Vietnam to estimate the prevalence of HPV 16 and/or 18 infections and to explore the distribution of other high risk types of HPV among married women in these provinces., Methods: The study employed a cross-sectional design with multistage sampling. The sample size included 4500 married women in two rounds (aged ranged from 18-69 years old, median age: 40 year old). Participant were randomly selected, interviewed and given gynaecological examinations. HPV infection status (by real-time PCR kit using TaqMan probe) and HPV genotyping test (by Reverse dot blot) were done for all participants., Results: The prevalence of cervical infection with HPV type 16 and/or 18 among married women in this study ranged from 3.1% to 7.4%. Many positive HPV cases (ranged from 24.5% to 56.8%) were infected with other type of high risk HPV which can lead to cervical cancer and cannot prevented by currently available vaccines. In addition to HPV 16 and/or 18, most common types of high risk HPV were types 58, 52, 35 and 45. Awareness about HPV and HPV vaccines was still low in the study samples., Discussion: While it is relevant to implement an HPV vaccine campaign in Viet Nam, it is important to note that one can be infected with multiple types of HPV. Vaccination does not protected against all type of high risk HPV types. Future vaccine campaigns should openly disclose this information to women receiving vaccines., Conclusion: High prevalence of infection with HPV high risk types was observed in this study. As HPV infection has a high correlation with cervical cancer, this study emphasizes the need for both primary prevention of cervical cancer with HPV vaccines as well as secondary prevention with screening.

Objective: Co-factors for cervical cancer, including oral contraceptive (OC) use, smoking and multiparity have been identified; however, the stage at which they act in cervical carcinogenesis is not clear. We compared established risk factors among women with CIN2 and CIN3 to evaluate the heterogeneity of these factors in precancer and also assessed their role during cervical carcinogenesis., Methods: The current analysis included 2783 women with various stages of cervical disease who were enrolled in the Study to Understand Cervical Cancer Early Endpoints and Determinants (SUCCEED) and the Biopsy Study. Associations of co-factors within cervical precancer and at different stages of cervical carcinogenesis were estimated using logistic regression., Results: Long-term OC use (10+years vs. never: OR=2.42, 95% CI: [1.13-5.15]), multiparity (3+ births vs. nulliparous: OR=1.54 [1.04-2.28]), smoking (ever vs. never: OR=1.95 [1.48-2.58]), and no Pap test in the previous five years (2.05 [1.32-3.17]) were positively associated with CIN3 compared to CIN2. We observed that long-term OC use, parity and smoking were associated with an increased risk of CIN3 compared to

The prevalence of cervical and anal human papillomavirus (HPV) and risk factors associated with infections were evaluated in a cross-sectional study of 211 adult women in American Samoa. Overall, 53% of women reported ever having a Pap smear. Cervical and anal HPV was detected in 10% and 16% of women, respectively; 4% of women had concurrent cervical and anal HPV. The most common cervical genotypes were HPV 6, HPV 16, and HPV 53. Cutaneous HPV types were detected in 40% of anal infections. Cervical HPV infection was associated with anal HPV (age-adjusted odds ratio = 3.32, 1.10-10.00). After age adjustment, cervical HPV was associated with being unmarried, postsecondary education, hot running water at home, multiple sexual partners, nulliparity, condom use, and other contraceptive methods. In multivariate analyses, only age remained associated with cervical HPV and anal HPV. Cervical and anal HPV was more prevalent among younger women; only anal HPV was detected in older women.