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Infection with human papillomavirus (HPV) typically leads to cervical cancer, skin related cancers and many other tumors. HPV is mainly responsible for evading immune tumor monitoring in HPV related cancers. Toll like receptors (TLRs) are particular pattern recognition molecules. When the body is facing immune danger, it can lead to innate and direct adaptive immunity. TLR plays an important role in initiating antiviral immune responses. HPV can affect the expression level of TLR and interfere with TLR related signaling pathways, resulting in sustained viral infection and even carcinogenesis. This paper introduces the HPV virus and HPV related cancers. We discussed the present comprehension of TLR, its expression and signaling, as well as its role in HPV infection. We also provided a detailed introduction to immunotherapy methods for HPV related diseases based on TLR agonists. This will provide insights into methods that support the therapeutic method of HPV related conditions with TLR agonists [ABSTRACT FROM AUTHOR]

Human genital papilloma virus infection is the most prevalent sexually transmitted infection in the world. It is estimated that more than 75% of sexually active women contract this infection in their lifetime. In 80% of young women, there is the clearance of the virus within 18–24 months. In developed countries, oral squamous cell carcinoma (OSCC) is now the most frequent human papilloma virus (HPV)-related cancer, having surpassed cervical cancer, and it is predicted that by 2030 most squamous cell carcinomas will be the HPV-related rather than non-HPV-related form. However, there are currently no screening programs for oral cavity infection. While the natural history of HPV infection in the cervix is well known, in the oropharynx, it is not entirely clear. Furthermore, the prevalence of HPV in the oropharynx is unknown. Published studies have found wide-ranging prevalence estimates of 2.6% to 50%. There are also conflicting results regarding the percentage of women presenting the same type of HPV at two mucosal sites, ranging from 0 to 60%. Additionally, the question arises as to whether oral infection can develop from genital HPV infection, through oral and genital contact or by self-inoculation, or whether it should be considered an independent event. However, there is still no consensus on these topics, nor on the relationship between genital and oral HPV infections. Therefore, this literature review aims to evaluate whether there is evidence of a connection between oral and cervical HPV, while also endorsing the usefulness of the screening of oral infection in patients with high-risk cervical HPV as a means of facilitating the diagnosis and early management of HPV-related oral lesions. Finally, this review emphasizes the recommendation for the use of the HPV vaccines in primary prevention in the male and female population as the most effective means of successfully counteracting the increasing incidence of OSCC to date. [ABSTRACT FROM AUTHOR]

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IFN-ε is essential in combating viral infections, particularly in epithelial cells and protected mucosal tissues. Its protective effects have been demonstrated against HSV2, Zika virus, HIV and SARS-COV2. However, the specific expression and role of IFN-ε in skin keratinocytes and HPV infection are still not fully understood and require further investigation. In this study, we aimed to investigate the functions and expression mechanism of IFN-ε in keratinocytes during HPV infection and the progression of condyloma acuminata. Keratinocytes isolated from biopsied CA warts and normal skins samples were analyzed by MeRIP-seq analysis. IFN-ε and WTAP in CA warts and normal skins were analyzed by immunostaining and qPCR. In this study, we identified IFN-ɛ was markedly upregulated in CA warts and HPV-infected keratinocytes. IFN-ɛ expression also showed negatively correlation with the size of CA warts (R=−0.4646, P = 0.009). IFN-ɛ suppressed the susceptibility of HPV infection directly. m6A analysis reveals WTAP is a key m6A writer promoting the m6A modification of IFNE mRNA. Our research suggests that IFN-ɛ is an important Type I IFN cytokine involved in the development of genital warts. Furthermore, we found that HPV infection affects the m6A modifications of IFNE through a mechanism dependent on WTAP. This study provides insights into the innate immune response of the host to HPV infection and may contribute to the development of future strategies for regulating innate immunity to treat genital warts. • HPV infection induces IFN-ɛ expression in keratinocytes. • IFN-ɛ shows negative correlation with the development of condyloma acuminata. • IFN-ɛ suppressed the susceptibility of HPV infection. • WTAP regulates the expression of IFN-ɛ by m6A modification. [ABSTRACT FROM AUTHOR]

Background: The human papillomavirus (HPV) is a virus that only infects epithelial cells. Skin and mucosal lesions, as well as malignancies, are usually associated with it. In anogenital carcinogenesis, HPV is a key player. Persistent HPV infections have been linked to an increased risk of developing cervical cancer in several studies. The objective of the current study is the detection of HPV-DNA in cutaneous and genital warts by polymerase chain reaction (PCR) and to evaluate their possible association with malignant and non-malignant conditions. Patients and methods: This study comprised 24 patients. They are classified into 4 groups (common wart, planter wart, genital wart and cancer cervix groups) according to the clinical and pathological results. Biopsies from lesions were subjected to DNA extraction. Extracted DNA was amplified in the PCR reaction For the purpose of detecting low-risk HPV Samples found to be positive by PCR were then exposed to an additional amplification in order to find high-risk forms of HPV. Results: revealed that low risk HPV-DNA was detected in 60% among common wart group, 26.6% among genital wart group and 13.3% among cancer cervix group. Meanwhile, it was not detected in planter wart group, with overall detection of HPV-DNA in 62.5 % of the study groups. About 46.7% of the positive cases had high-risk HPV-DNA. Conclusion: Common wart is the most benign lesions as it rarely converts to malignancy. Genital HPV infection was detected in both malignant and nonmalignant conditions. HPV is a potential risk for cervical neoplasia among Egyptian women. [ABSTRACT FROM AUTHOR]

Genital wart is one of the most commonly found human mucosal viral infection caused by the Human Papillomavirus (HPV). Genital warts can present as papules, plaques or blisters that look like a pink, brown cauliflower, or flesh-coloured mass. The treatment modalities for genital warts that are currently available are focused on eliminating the genital warts growth instead of addressing and controlling the underlying HPV infection. A little evidence has been provided regarding the existing treatment modalities in terms of their effectiveness in eliminating genital warts in the long term or that they have a key role in the prevention and development of malignant genital warts. Moreover, the treatment modalities that are currently used are different in terms of price, side effects, dosing regimen, treatment duration, and efficiency for managing genital warts. However, it is important to consider that the treatment modalities are often tailored to each patient depending on the level of HPV spread, areas that have been infected, and other comorbid chronic diseases. [ABSTRACT FROM AUTHOR]

Background: Human papilloma virus (HPV) causes multiple anogenital diseases including cervical cancer and is the most common sexually transmitted infection. Healthcare resource utilization (HRU) associated with HPV-related anogenital diseases includes diagnostic and disease specific treatment regimens. A recent study showed disease burden of young women aged 23-25 years, who were the first populations eligible to receive HPV vaccination after its introduction in Germany. Cost for the German statutory health insurance (SHI) due to HPV‑related anogenital diseases in this population are unknown. This study aimed at assessing HRU and costs related to HPV-associated anogenital diseases for the Germany SHI.Methods: We used a retrospective, matched cohort design to leverage the prior identified cohort of 23-25-year-old women born between 1989-1992 diagnosed with HPV-related anogenital disease from the Institute for Applied Health Research Berlin (InGef) Research Database. German SHI claims data from 2012-2017 were analyzed. The prior identified cases were matched (direct, without replacement) to women without anogenital diseases (1:10 ratio). HRU and costs for inpatient care, outpatient care, and pharmaceutical during a 3-year observation period were determined for both cases and controls and increments between the groups were assessed.Results: 2,972 women diagnosed with anogenital diseases (cases) who were matched to 29,720 women without anogenital diseases (controls). Cases had more outpatient visits (52.4 visits vs. 39.2 visits) and more cases (45.2% vs. 31.7%) were hospitalized at least once in the 3‑year observation period. Most common outpatient procedures performed in cases were conization of the cervix uteri (4.4% cases; n < 5 controls), followed by other excision and destruction of diseased tissue of the cervix uteri (3.1% in cases; 0.0% in controls). Median difference in total healthcare costs of €684 (mean difference: €1,089, 95%CI: €752-1,426) suggest that HPV-related anogenital diseases were responsible for approximately €3.2 Million more healthcare costs for the identified cases in the four birth cohorts within the 3‑year observation period in the InGef Research Database. Costs were mainly driven by outpatient care (41.6% of total costs).Conclusion: In Germany, HPV-related anogenital diseases among young women are associated with considerable HRU and financial expenditures, mostly driven by outpatient care. [ABSTRACT FROM AUTHOR]

Background: Genital warts are a common sexually transmitted disease (STD), and there is no method that completely prevents its recurrence. Recently, zinc has been used in the treatment of cutaneous warts. Nondestructive action, ease of use, and promising results with low chances of relapse were reflected in the treatment. These effects may arise from the immunomodulatory activity of zinc in the event of a viral infection.Objectives: This study was aimed at identifying the relationship between the serum zinc level and the clinical characteristics of patients with genital warts.Materials and Methods: A case-control study was conducted. Genital warts were diagnosed by clinical examination, and disease severity was demonstrated based on the number of affected sites or the spread of lesions. The serum zinc level was measured using atomic absorption spectrophotometry.Results: A total of 78 patients with genital warts and 78 healthy volunteers were enrolled in the study. The mean serum zinc level in the genital wart group was lower than that in the control group (81.83 ± 13.99 μg/dL vs. 86.66 ± 17.58 μg/dL); however, this difference was not statistically significant (P > 0.05). The mean concentrations of serum zinc in patients having more than one affected site, spread > 2 cm2, or ten or more lesions were significantly lower than those of the control group (P < 0.05).Conclusions: The results suggested that severe genital warts may be associated with a low serum zinc level in patients. [ABSTRACT FROM AUTHOR]

Sexually transmitted infections (STIs) represent a major cause of morbidity in women and men worldwide. The main aim of this study was to perform a comparative analysis of the incidence of sexually transmitted viral infections in 2010–2015 in Poland, taking into account the administrative division of the country into provinces. This was a retrospective study. The analysed data came from the Centre for Health Information Systems of the Ministry of Health and the National Institute of Public Health-National Research Institute and constituted information from the epidemiological surveillance system in Poland. We collected data on the incidence of the following diseases: genital herpes (HSV), genital warts, human immunodeficiency virus (HIV) infection and acquired immunodeficiency syndrome (AIDS). The key groups with the highest risk of infection were young people between 20 and 29 years of age. The reported data on the incidence of genital herpes in Poland (n = 3378; 1.5/100,000) showed a downward trend, which does not coincide with global trends. Genital warts were the most frequent genital infections in Poland (n = 7980; 3.46/100,000), with significant regional variation. Over the analysed period, the situation of newly detected HIV infections seemed to be stable (n = 7144; 3.1/100,000). The incidence of these infections appeared to be highly correlated with urbanisation rates, which was not confirmed in the case of other analysed infections. The worsening epidemic situation with respect to sexually transmitted infections, the inefficiency of the current surveillance system and the reduction in funding for diagnosis and prevention, combined with inadequate legal solutions, make it necessary to undertake new legal and organisational measures aimed at improving the reproductive health in Poland in terms of sexually transmitted infections. [ABSTRACT FROM AUTHOR]

Oral cavity and oropharynx cancer associated with human papil loma virus infection, particularly in young people who are continuously exposed to this virus, is a serious public health problem worldwide, especially for high-risk strains that are most associated with premalignant lesions and tumors. These neoplasms remain asymptomatic for a long time and, when they occur, they are already at an advanced stage. If diagnosed and treated early, oral cancer induced by human papilloma virus allows for high survival, as it often has a more favorable prognosis than oral cancers not directly related to viral infection. In this study, the presence of different high-risk and low-risk HPV strains was investigated to assess the epidemiological status in a population of healthy individuals. Two types of samples, one from the tonsils and one from the base of the tongue, were collected from 2015 healthy individuals of different sex and age. A total of 1885 DNA samples belonging to 1285 patients were tested for the presence of 11 high-risk HPV types plus 4 low-risk HPV types using real-time PCR. Of the patients' DNA samples screened for 15 HPV types, only four samples were positive, all of which were taken from male smokers. These results indicate that newly acquired oral oncogenic HPV infections in the healthy population are rare and, in many cases, controversial. Therefore, more studies are needed to ensure fewer variations in outcomes and a greater clarification of HPV infection and its prevalence in the oropharynx of the healthy population, and to guide efforts to prevent the development of this infection which, if undiagnosed, can lead to the onset of malignant tumors in the oral cavity. [ABSTRACT FROM AUTHOR]

HPV, a sexually transmitted viral infection, is the etiological agent of significant dermatologic disease including benign anogenital warts and invasive cancers. Sexual and gender minority individuals are particularly vulnerable to HPV‐associated disease due to reduced vaccination rates in these cohorts, low awareness of HPV, lack of provider recommendation, and inadequate consensus guidelines on screening and prevention in these individuals. A targeted approach is needed with regards to vaccination in all children —especially those from racial, ethnic, sexual, and gender minorities; provider recommendation, especially from pediatric dermatologists, is crucial. Effort must also be made to use transgender and non‐binary affirming language as dividing vaccination programs by anatomic sex and sexuality reinforces problematic notions of gender identity and sexuality, isolating the most vulnerable. [ABSTRACT FROM AUTHOR]

Background: The primary goal of human papillomavirus (HPV) vaccination is to reduce morbidity and mortality from HPV-associated disease, especially cervical cancer. We determined the real-world effectiveness of HPV vaccination against cervical cancer.Methods: The study included women aged 17-30 years living in Denmark October 2006-December 2019. From nationwide registries, information on HPV vaccination and cervical cancer diagnoses were retrieved. Incidence rate ratios (IRRs) with 95% confidence intervals (CIs) for cervical cancer according to vaccination status were estimated using Poisson regression with HPV vaccination treated as a time-varying variable and stratified by age at vaccination. We adjusted for attained age, education, and ethnicity. To address the effect of prevalent disease, different buffer periods were used, with 1-year buffer period as primary analysis.Results: The cohort comprised 867 689 women. At baseline, 36.3% were vaccinated at age 16 years and younger, and during follow-up, 19.3% and 2.3% were vaccinated at ages 17-19 years and 20-30 years, respectively. For women vaccinated at ages 16 years and younger or 17-19 years, the IRRs of cervical cancer were 0.14 (95% CI = 0.04 to 0.53) and 0.32 (95% CI = 0.08 to 1.28), respectively, compared with unvaccinated women. In women aged 20-30 years at vaccination, the incidence rate was higher than among unvaccinated women (IRR = 1.19, 95% CI = 0.80 to 1.79) but slightly decreased with increasing buffer period (IRR = 0.85, 95% CI = 0.55 to 1.32, with 4-year buffer period).Conclusion: HPV vaccine effectiveness against cervical cancer at the population level is high among girls vaccinated younger than age 20 years. The lack of immediate effect in women vaccinated at age 20-30 years points to the importance of early age at vaccination. [ABSTRACT FROM AUTHOR]

Background: External genital warts (EGW), also known as condyloma acuminata (CA) is caused by Human Papilloma Virus (HPV) and is the most frequent sexually transmitted viral infection in the world with a worldwide prevalence range of 5% to 20%. Objective: The aim of the study is to determine the epidemiologic characteristics of the disease and its relation to abnormal pap smear testing and abnormal serologic testing. Setting and Methodology: a cross sectional retrospective study conducted at Bahrain Force Defence (BDF) Hospital between November 2012 to December 2017 who attended dermatology clinic for CA. A total of 3482 patients' visit were obtained. With inclusion and exclusion criteria only 195 individuals (112 (57%) females and 83 (43%) males) were included in the study. Results: Epidemiologic characteristics were found as following; majority were between 26-35 years of age 84 (43%), married 136 (70.47%) and having had the wart for months before seeking dermatologist care 93 (47.7%). The two most common sites identified were the groin (31.79%) and labia (22.05%). In female study subjects, 65 underwent pap smear testing of whom 11 tested positives for HPV. Out of 136 study subjects who were serologically tested for HIV, HBsAg, HCV and VDRL/TPHA, 5 males and 1 female showed positive results for either or a combination. Conclusion: Educating the public and raising awareness about the EGW could potentially help control its spread by emphasizing earlier doctor visits and educating healthcare workers to develop that habit of screening the patient's spouse. Routine screening and serologic testing of patients is recommended to detect high risk sexually transmitted diseases that could be present alongside the EGW. [ABSTRACT FROM AUTHOR]

Background: Vaccination against human papillomavirus (HPV) has proven to be effective against severe cervical lesions and genital warts, whereas no previous study has provided real-world data on the HPV vaccine effectiveness against high-grade vulvovaginal lesions.Methods: A cohort of all women age 17-26 years living in Denmark during 2006-2019 was followed in nationwide registers for individual-level information about HPV vaccination and first diagnoses of vulvar and vaginal high-grade squamous intraepithelial lesions (HSIL+) or worse. The cumulative incidence of vulvar and vaginal HSIL+, respectively, was estimated with the Aalen-Johansen estimator, and Cox proportional hazards regression was used to estimate hazard ratios (HRs) for vulvar and vaginal lesions separately, comparing women vaccinated at age 16 years or younger and at age 17-26 years with unvaccinated women.Results: The cohort consisted of 514 537 women, of which 50.6% were vaccinated at baseline (<16 years), 31.8% were vaccinated during follow-up (17-26 years), and 17.6% remained unvaccinated. The cumulative incidence was less than 0.6‰ for vulvar HSIL+ and less than 0.2‰ for vaginal HSIL+. Adjusted analyses showed reduced HRs for both vulvar (HR = 0.22, 95% confidence interval = 0.13 to 0.38) and vaginal HSIL+ (HR = 0.16, 95% confidence interval = 0.04 to 0.55) for women vaccinated at age 16 years or younger compared with unvaccinated women. For women vaccinated at 17-26 years of age, the reductions in HRs were smaller for vaginal HSIL+ and close to 0 for vulvar HSIL+.Conclusions: HPV vaccination before 17 years of age reduces the risk of vulvar and vaginal HSIL+ based on real-world data. [ABSTRACT FROM AUTHOR]

Background: Combined with cancer screening programs, vaccination against human papillomavirus (HPV) can significantly reduce the high health and economic burden of HPV-related disease in Japan. The objective of this study was to assess the health impact and cost effectiveness of routine and catch-up vaccination of girls and women aged 11-26 years with a 4-valent (4vHPV) or 9-valent HPV (9vHPV) vaccine in Japan compared with no vaccination.Methods: We used a mathematical model adapted to the population and healthcare settings in Japan. We compared no vaccination and routine vaccination of 12-16-year old girls with 1) 4vHPV vaccine, 2) 9vHPV vaccine, and 3) 9vHPV vaccine in addition to a temporary catch-up vaccination of 17-26 years old girls and women with 9vHPV. We estimated the expected number of disease cases and deaths, discounted (at 2% per year) future costs (in 2020 ¥) and discounted quality-adjusted life years (QALY), and incremental cost effectiveness ratios (ICER) of each strategy over a time horizon of 100 years. To test the robustness of the conclusions, we conducted scenario and sensitivity analyses.Results: Over 100 years, compared with no vaccination, 9vHPV vaccination was projected to reduce the incidence of 9vHPV-related cervical cancer by 86% (from 15.24 new cases per 100,000 women in 2021 to 2.02 in 2121). A greater number of cervical cancer cases (484,248) and cancer-related deaths (50,102) were avoided through the described catch-up vaccination program. Routine HPV vaccination with 4vHPV or 9vHPV vaccine prevented 5,521,000 cases of anogenital warts among women and men. Around 23,520 and 21,400 diagnosed non-cervical cancers are prevented by catch-up vaccination among women and men, respectively. Compared with no vaccination, the ICER of 4vHPV vaccination was ¥975,364/QALY. Compared to 4vHPV, 9vHPV + Catch-up had an ICER of ¥1,534,493/QALY.Conclusions: A vaccination program with a 9-valent vaccine targeting 12 to 16 year-old girls together with a temporary catchup program will avert significant numbers of cases of HPV-related diseases among both men and women. Furthermore, such a program was the most cost effective among the vaccination strategies we considered, with an ICER well below a threshold of ¥5000,000/QALY. [ABSTRACT FROM AUTHOR]

Ustekinumab is a fully human monoclonal antibody targeting the pro-inflammatory cytokines interleukin (IL)-12 and IL-23 approved for the treatment of psoriasis and psoriatic arthritis. We report a case of a patient treated for chronic plaque psoriasis with ustekinumab who developed bulky condyloma acuminata shortly after initiating the treatment. Although ustekinumab has already been described in literature associated with other forms of human papilloma virus skin infections, this is the first case to our knowledge in which ustekinumab is associated with genital warts. [ABSTRACT FROM AUTHOR]

Cervical cancer, caused by HPV infection, is responsible for more than 311  000 preventable deaths every year. A global call to accelerate efforts to eliminate this disease has generated a new global strategy proposing ambitious, but achievable, targets for HPV vaccination of girls, and screening and treatment of women. The present paper addresses the suboptimal access to HPV vaccination in low-income and lower-middle-income countries (LICs/LMICs), where the burden of disease weighs most heavily, in part through co-infection with HIV. A proposed framework for action was formulated by first reviewing the reasons underlying gaps in HPV vaccine coverage. Good practices from recent introductions of HPV vaccine at scale in LICs/LMICs were then assessed based on targeted literature reviews and the experience and views of the authors. Difficulties in uptake and coverage of the HPV vaccine relate to the costs of the vaccine and service delivery, lack of prioritization, the challenges of vaccinating adolescents, and shortage of vaccines as the supply failed to keep pace with the rapid expansion in global demand, including from LICs/LMICs. The framework for action calls for new strategic thinking to consolidate global learning and invigorate operationalization at a country level. [ABSTRACT FROM AUTHOR]

Women infected by human immunodeficiency virus (HIV) are more likely to manifest oncogenic viral infections including human papillomavirus (HPV). It was investigated the HPV prevalence, genotype distribution and HPV relationship with cervical lesions among women living with HIV in Sergipe state, Northeast Brazil. A prevalence survey was conducted including 270 HIV‐infected women who attended the reference center for HIV in Sergipe from August 2014 to November 2017. Cervical samples were processed by the polymerase chain reaction for HPV‐DNA detection. Among the 270 HIV‐infected women, 190 (70.4%) were between 26 and 49 years old and 159 (55.6%) were coinfected with HPV. Among the coinfected women, 24 viral types were identified; 113 (72%) subjects had high‐risk HPV types, and the most prevalent was HPV 16 (53/35.3%). Positive HPV status was statistically associated with having 0 to 8 years of schooling compared with ≥9 years of schooling; and have been diagnosed with HIV infection less than 5 years ago compared with more than 10 years. Cytological abnormalities were found in 13.4% (31/231) of women, most with high‐grade squamous intraepithelial lesions (16/51.6%). However, of women who had no cytological lesions or malignancy (200/86.6%), almost half were HPV DNA‐positive (99/49.5%). In conclusion, the prevalence of HPV among women living with HIV in Sergipe was high. There was a high frequency of high‐risk HPV infection, and a wide diversity of genotypes were detected, with HPV 16 being the most frequent. Highlights: Women infected by HIV are more likely to manifest oncogenic viral infection including human papillomavirus (HPV);The prevalence of HPV and its genotypes vary with the location and settings;A high prevalence of HPV infection and a wide diversity of genotypes was found in HIV‐positive women in Sergipe state, Northeast Brazil;Twenty‐four HPV genotypes were detected, with a predominance of high‐risk HPV types, including HPV 16, 31, 33, 35, 45, and 58;Almost half of women without cytological abnormalities are coinfected with HPV, and most with high‐risk genotypes. [ABSTRACT FROM AUTHOR]

Introduction: Human papillomavirus (HPV) is emerging as a risk factor for esophageal squamous carcinoma. The prognostic value of the HPV status has been investigated. However, the results are much controversial.Aim: This study aims to document the association of HPV infection and mutation of p53 gene in esophageal squamous cell carcinoma (ESCC) and its impact on treatment outcome.Subjects and Methods: The study was conducted over a period of 12 months. A total of 30 cases of ESCC who were primarily to be treated with radiotherapy/chemoradiotherapy were included in the study. All the tissue samples for biopsy were subjected to immunohistochemistry to study p53 and p16 expression, which is a surrogate marker for HPV. The patients were treated by radiotherapy alone or concurrent chemoradiotherapy depending on performance status and stage of disease. The impact of p16 and p53 on overall survival (OS) and disease-free survival (DFS) was determined.Results: The median OS of HPV-positive patients was 22 months (95% confidence interval [CI] 12-31) as compared to 13 months (95% CI 7-18) for HPV-negative patients (P = 0.298). The median DFS for HPV-positive patients was 16 months (95% CI 7-24) as compared to 5 months (95% CI 4-6) for HPV-negative patients (P = 0.048). The median OS of p53-positive patients was 13 months (95% CI 6.7-19) as compared to 22 months (95% CI 12.7-31.2) for p53-negative patients (P = 0.080). The median DFS for p53-positive patients was 5 months (95% CI 3.7-6.2) as compared to 22 months (95% CI 15.7-29.4) for p53-negative patients (P = 0.014).Conclusion: Clinical findings of our result can be used to sum up that both HPV infection and p53 mutation status are reliable biomarkers and can help clinicians to predict treatment outcome and prognosticate patients better. [ABSTRACT FROM AUTHOR]

Objective: We aim to illustrate and evaluate the prevalence and distribution pattern of cervical human papilloma virus (HPV) genotypes on La Réunion Island, a French overseas territory, with the aim to guide future vaccination policies.Study Design: Between January 2008 and July 2012, files of women undergoing gynaecological examination were retrospectively evaluated at the University Hospital, Reunion Island. Inclusion criteria required cervical biopsies with histopathological diagnosis of high-grade lesions or cancer and ASCUS Pap Smears (atypical squamous cells undetermined significance) results. The INNO-LIPA HPV Genotyping Extra® test was used for HPV genotyping.Results: A total of 401 ASCUS Pap Smears and 94 cervical biopsies were analyzed, of which 162 smears and 63 biopsies were HPV DNA positive (40.4 % and 67 % respectively). Detailed breakdowns of HPV genotype-specific distribution reported prevalence of HPV 16, 31, 33, 51 and 52. Of the 63 HPV-positive biopsies, 61 (96.8 %) contained at least one HPV genotype that is contained in the 9-valent HPV vaccine. The incremental preventable fraction of HPV infections that could have been added by the new 9-valent vaccine to the current bivalent vaccine was estimated at 26.2 %.Conclusions: Immunization with 9-valent vaccine should be effective, and in the long term, may reduce cervical cancer incidence in Reunion Island. Nevertheless, vaccination rates and coverage need to be maintained and improved. [ABSTRACT FROM AUTHOR]

To evaluate the efficacy and safety of 1% and 5% 5-fluorouracil (5-FU) creams compared with 90% trichloroacetic acid (TCA) for the treatment of anogenital warts. we conducted a randomised controlled study in 72 subjects allocated to three groups: 1% 5-FU, 90% TCA and 5% 5-FU; 90% TCA was administered once a week, whereas 5-FU cream was applied three times a week. Response to therapy and side-effects were evaluated weekly for seven weeks. Evaluation at week 7 demonstrated that there was no significant difference in the efficacy between 1% 5-FU cream and 90% TCA (p = 0.763) or between 5% 5-FU cream and 90% TCA (p = 0.274). Subjective side-effects with 1% 5-FU were significantly milder than 90% TCA; however, significantly milder objective side-effects were observed only at weeks 2, 6 and 7. The subjective side-effects with 5% 5-FU were also significantly milder than 90% TCA; however, significantly milder objective side-effects were observed only at week 2. 5-FU may become an alternative topical therapy as it offers the benefit of self-application; furthermore, a concentration of 1% 5-FU cream is recommended due to milder side-effects. [ABSTRACT FROM AUTHOR]

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 cancers 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. [ABSTRACT FROM AUTHOR]

Background: Human papillomaviruses (HPVs) have been divided into mucosal and cutaneous types according to their primary epithelial tissue tropism. However, recent studies showed the presence of several cutaneous types in mucosal lesions and healthy mucosa from different anatomical sites.Methods: Here, the HPV prevalence and type-specific distribution were assessed in a variety of mucosal samples from 435 individuals using a combination of two established broad-spectrum primer systems: Gamma-PV PCR and CUT PCR.Results: Overall HPV prevalence in anal canal swabs, cervical cancer biopsies, genital warts and oral swabs was 85, 47, 62 and 4%, respectively. In anal canal swabs, Alpha-PVs were most frequently found (59%), followed by Gamma- (37%) and Beta-PVs (4%). The prevalence and persistence of HPV infection in the anal canal of 226 individuals were further explored. Overall HPV, Gamma-PVs and multiple HPV infections were significantly higher in men vs. women (p = 0.034, p = 0.027 and p = 0.003, respectively); multiple HPV infections were more common in individuals ≤40 years (p = 0.05), and significantly higher prevalence of Gamma-PVs and multiple HPV infections was observed in HIV-1-positive vs. HIV-1-negative individuals (p = 0.003 and p = 0.04, respectively). Out of 21 patients with follow-up anal swabs, only one persistent infection with the same type (HPV58) was detected.Conclusions: Our findings suggest that Gamma-PVs (except species Gamma-6) are ubiquitous viruses with dual muco-cutaneous tissue tropism. Anal canal Gamma-PV infections may be associated with sexual behavior and the host immune status. This study expands the knowledge on Gamma-PVs' tissue tropism, providing valuable data on the characteristics of HPV infection in the anal canal. [ABSTRACT FROM AUTHOR]

Background: Studies in countries with high human papillomavirus (HPV) vaccination coverage have demonstrated marked reductions in anogenital wart (AGW) incidence. Our goal was to assess the impact of HPV vaccination in a population with suboptimal coverage by comparing AGW incidence trends in the years before and after vaccine introduction.Methods: We conducted a retrospective analysis of AGW incidence trends using an ecologic study design among 11- through 39-year-olds enrolled at Kaiser Permanente Northwest. We defined incidence as the proportion of persons who had a new AGW diagnosis for each calendar year in the prevaccine periods (2000 through 2006 for female individuals, 2000 through 2010 for male individuals) and the postvaccine periods (2007 through 2016 for female individuals, 2011 through 2016 for male individuals). We also described cumulative HPV vaccination coverage.Results: The average annual AGW incidence rates in the prevaccine periods were 27.8 per 10,000 in female individuals and 26.9 per 10,000 in male individuals. In the postvaccine periods, AGW incidence rates decreased by 31% (P < 0.001) in female individuals and 10% (P = 0.006) in male individuals; the largest reductions were observed in 15- to 19-year-old female individuals (67%, P < 0.001) and male individuals (45%, P < 0.001). Three dose HPV coverage rates were less than 50% in all age groups and both sexes.Conclusions: In a population of young adults with moderate HPV vaccination coverage, we observed declines in AGW incidence among both female and male year after the introduction of HPV vaccination. The largest incidence reductions were observed in 15- to 19-year-olds who were most likely to have been vaccinated. [ABSTRACT FROM AUTHOR]

Human papilloma virus is the primary causative agent for cervical cancer, and vaccination is the primary means of preventing anogenital cancers caused by human papilloma virus infection. Despite the availability of human papilloma virus vaccines for more than a decade, coverage rates lag behind those for other vaccines. Public concerns regarding safety of human papilloma virus vaccines have been identified as an important barrier to vaccination, including concerns that the human papilloma virus vaccine may cause primary ovarian insufficiency, driven in part by isolated reports of ovarian failure following the human papilloma virus vaccine. We summarize published peer-reviewed literature on human papilloma virus vaccines and primary ovarian insufficiency, reviewing information contained in the case reports and series. Healthcare providers should address any patient concerns about primary ovarian insufficiency and the human papilloma virus vaccine by acknowledging the case reports but noting the lack of association found in a recently published epidemiologic study of approximately 60,000 female individuals. Current evidence is insufficient to suggest or to support a causal relationship between human papilloma virus vaccination and primary ovarian insufficiency. [ABSTRACT FROM AUTHOR]

HPV status in relation to occurrence of oral and oropharyngeal carcinomas has been a less explored arena in the Indian Subcontinent. Lack of data on variation in the occurrence of high risk HPVs across India necessitates a region wise update on HPV status. The literature search shows current evidence of overall HPV prevalence to be 3.1 to 73.6% throughout the country and most frequently isolated high risk type was HPV16. The incidence of oral cancer especially posterior tongue associated cancers are on the rise and is becoming more common in non-tobacco users and further studies in this regard might open the way for further insight into head and neck cancers caused by HPVs in India. This brief report summarizes the need for a more detailed analysis in regard to the prevalence data obtained and the methodologies used to arrive at the same. [ABSTRACT FROM AUTHOR]

Background: Chronic viral infections caused by highly contagious human papillomaviruses (HPVs) from the alpha genus are a substantial risk factor for tumour diseases. Objectives: The goal of this study was to compare the HPV infection pattern with histology in a patient group of immunocompromised HIV+ and non‐immunocompromised patients with anal intraepithelial neoplasia. Materials and Methods: Tissue samples (n = 210) from the anogenital area of 121 patients underwent retrospective histological and molecular examination for HPV DNA prevalence by chip analysis. The study was part of a cancer screening from the Dermatology Department of the LMU Munich, Germany. All data were collected and processed anonymously. Results: HPV 6 or 11 are more abundant in tissue samples from histologically diagnosed condylomata acuminata (47.7%) compared to grade 1, 2, and 3 intraepithelial neoplasias (IN 1‐3). Detection of high‐risk (hr) alpha‐HPV DNA was significantly higher in tissue samples from IN 3 (67.5%) compared to IN 1 and 2 (12.9%), and compared to condylomata acuminata (29.5%). No HPV types were detected in histologically unremarkable tissue samples. There was a significant association between the prevalence of HPV 16 and the classifications IN 1 to IN 3 (χ2 (2) = 13.62, P = 0.001). We identified a significant correlation between the prevalence of high‐risk and low‐risk (lr) HPV types and HIV, especially mixed infections of different HPV types correlated with high‐grade IN. Based on the present data, we suggest the risk of carcinoma in HIV+/− patients (RICH) score and test it in the 121 patients. Conclusions: hr alpha‐HPVs, mainly HPV 16, are associated with increased oncogenic potential of premalignant lesions (IN 1‐3), especially in HIV+ patients. Based on the combination of HIV/HPV‐testing and histological analysis, we identified correlations that could potentially forecast the risk of malignant transformation and summarized them in the form of RICH score. [ABSTRACT FROM AUTHOR]

Background: Fingolimod is used to reduce relapse rates in relapsing-remitting multiple sclerosis (MS). It is a sphingosine 1-phosphate (S1P) analogue having antagonistic effects on S1P receptors. Its immunosuppressive effect is due to reduced circulating lymphocyte numbers, and it may also be associated with impaired intrinsic cancer surveillance. Fingolimod side effects include increased rates and severity of viral infections particularly varicella zoster. Methods: We present five cases of chronic and treatment refractory warts associated with fingolimod therapy. Results: Each of the five cases presenting with chronic warts while receiving fingolimod therapy had prolonged periods of lymphopenia and improvements were seen following dose reduction or cessation of fingolimod. Conclusion: Cutaneous warts are associated with human papilloma virus (HPV) infection, suggesting an increased risk of other HPV-driven conditions such as cervical cancer following fingolimod administration. HPV viruses are responsible for approximately 90% of cervical cancers as well as a significant portion of anogenital cancers and have a high prevalence in sexually active adults. Given the reduced immune response to viral infections and potential impaired cancer surveillance in those receiving fingolimod, HPV vaccination and frequent assessment for the development of HPV-associated malignancies are recommended. [ABSTRACT FROM AUTHOR]

Objectives: In 2008, a national human papillomavirus (HPV) vaccination programme for females was introduced in England using the bivalent vaccine (HPV16 and 18 only). In 2012, the programme changed to offer the quadrivalent vaccine that includes protection against the two HPV types that cause the majority of anogenital warts (AGW; HPV6 and 11). We present data reporting AGW diagnoses in sexual health clinics (SHCs) in England to the end of 2017, including diagnoses among birth cohorts offered the quadrivalent vaccine.Methods: Using data from all SHCs across England, we performed ecological analyses to consider rates of AGW diagnoses by age, gender and sexual orientation. We tested for trends over time of diagnoses of AGW in young females, heterosexual males, and men who have sex with men (MSM) between the ages of 15 and 24 years during both bivalent (2009 to 2013) and quadrivalent (2014 to 2017) vaccine time periods using Poisson regression.Results: Between 2014 and 2017, there was strong evidence for a decreasing trend in the rate of AGW diagnoses at SHC among females aged 15-17 years from 257.5 to 45.7 per 100 000 population (82.3% decline) and same aged heterosexual males from 59.1 to 19.1 per 100 000 population (67.7% decline). The reductions in the incidence of AGW diagnoses in MSM aged 15-17 years were less clear (decreased by 13.6% between 2014 and 2017, from 129.9 to 112.2 per 100 000 population).Conclusions: The moderate, unexpected declines in AGW seen since the introduction of a high-coverage HPV vaccination programme using the bivalent vaccine are being followed, as expected, by much larger declines among females offered the quadrivalent vaccine and same-aged heterosexual males. Surveillance plans are in place to continue to monitor AGW diagnoses to evaluate the impact of both female and targeted MSM HPV vaccination on early disease outcomes. [ABSTRACT FROM AUTHOR]

Introduction: External ano-genital warts (AGWs) due to human papilloma virus infection are the most common sexually transmitted ano-genital lesions of viral origin worldwide. Treatments include topical chemicals/drugs, excisional surgery, cryosurgery, electrosurgery and laser surgery. Nitric-zinc complex (NZC) is a new topically applied solution containing nitric acid, zinc, copper and organic acids that induces a caustic effect on condyloma. The objective of this study was to investigate the efficacy and tolerability of NZC in the treatment of AGWs. Methods: Patients attending for AGWs between September 2016 and February 2018 were retrospectively studied. They received at least one NZC application for a maximum of four treatments (V0, V1, V2, V3) with average intervals of 25 days between sessions. Recurrences were evaluated at 3 and 6 months after clearance. Results: One hundred patients (70 males, 30 females) with a mean age of 36.39 years were studied. The total number of AGWs diagnosed at the baseline visit (V0) in all patients was 418 with a mean of 4.18 AGWs per patient. A wart cure rate of 92% was observed in ≤ 4 treatment sessions (383 lesions cured at visit 4, V4, out of 418 lesions at baseline), with a cure rate of 49% with only one NZC application. Complete clearance was observed in 25, 52, 72 and 84% of patients at V1, V2, V3 and V4, respectively. Relapses were observed in 29% of patients at 3 months and in 5% at 6 months. Of note, patients with ≤ 5 AGWs at V0 showed better clearance results than patients with > 5 lesions (p < 0.05). The treatment was well tolerated by most patients. Conclusion: NZC has been demonstrated to be effective for AGWs after 1–4 treatment sessions, obtaining a good response from the first application. The better response in patients with fewer warts suggests that the earlier diagnosis is made and treatment started, the better the expected results. Funding: ISDIN. [ABSTRACT FROM AUTHOR]