Nononcogenic Human Papillomavirus Research Articles

Introduction of E-Score: A gene expression score to characterize immunogenic versus oncogenic HPV expression in HNSCC.

6057 Background: Human Papillomavirus (HPV) integration in the human genome occurs in a majority of HPV(+) head and neck squamous cell carcinomas (HNSCC), with direct and indirect effects on host gene expression and tumorigenesis. Although previous studies showed that HPV integration in HNSCC is overrepresented in genes often somatically mutated in head and neck, lung, and urogenital cancers, reports are mixed for whether patients with HPV integration have worse clinical outcomes. These disparate results may be due to differences in how integration is defined. Integration can often lead to partial loss of the viral genome (e.g. HPV genes E1, E2, or E5) with retention of the oncogenes E6 and E7, which led to a low E2/E7 expression ratio being used as a biomarker for integration. Conversely, others have used the direct detection of DNA or RNA HPV-human breakpoints to identify tumors harboring integrated HPV. HPV integration and the retention or deletion of HPV genes can dramatically change the expression of HPV genes, and we hypothesize it also affects the host immune response. Hypothesis: Loss of non-oncogenic HPV genes relative to E6 and E7 levels reduces immunogenicity, leading to weakened immune cell infiltration and worse clinical outcomes. Methods: Bulk RNA sequencing data from HPV(+) HNSCC tumors (n = 136) was used to characterize the differences in retention or loss of HPV genes and calculate the E-Score as the sum of the logCPM of HPV genes E1, E2, E4, and E5 relative to E7. Cell type deconvolution was performed using ComBat to correct for batch effects, and CIBERSORTx to quantify cell type proportions within the tumor samples. Kaplan-Meier estimates of recurrence and overall survival (OS) were calculated, and Cox proportional hazards tests with covariates were used to test for association with recurrence and OS. To test the correlation between immune cell type inferred proportions and E-Score, T-Tests were performed between samples with high and low E-scores. Results: Low E-Score was significantly associated with recurrence (p = 0.012) but not with OS (p = 0.39) in the multivariate model accounting for age, tumor stage (AJCC8), smoking status, drinking status, BMI, marital status, and molecular tumor subtype (defined as IMU or KRT). For integration positive samples (n = 66), higher E-Score, suggesting lower rates of HPV gene loss, was correlated with higher percentages of dendritic cells (p = 0.044), macrophages (p = 0.021), and CD8+ T Cells (p = 0.024), but not CD4+ T cells (p = 0.14). This significance did not hold when looking at integration negative samples. Conclusions: These results suggest that HPV+ HNSCC patients with a loss of E1, E2, E4 and E5 tend to have less immune cell infiltration and are more likely to have recurrence. We conclude that E-Score is a potential prognostic biomarker of recurrence in HPV+ HNSCC and potential predictive biomarker for immunotherapy.

Prevalence of oral HPV among people living with HIV (PLHIV) in Pune, India

Background: People living with HIV (PLHIV) are at an increased risk of human papillomavirus (HPV)-related head and neck cancers (HNCs). However, there is little data on the prevalence of oral HPV among PLHIV in India, limiting the planning of oral HPV preventive strategies. Methods: We used cross-sectional data from an oral cancer screening study conducted at the antiretroviral therapy (ART) centre of Byramjee-Jeejeebhoy Government Medical College-Sassoon General Hospitals (BJGMC-SGH). PLHIV ≥21 years of age with no prior history of HNCs were enrolled. We determined the prevalence of high-risk oncogenic HPV (hrHPV) and low-risk non-oncogenic HPV (lrHPV) using real-time PCR and Next-Generation Sequencing. We used multinomial logistic regression to determine the prevalence ratios (PRs) of different sociodemographic, clinical, and behavioural predictors with hrHPV and lrHPV. Multivariable models were adjusted for age, sex, CD4 count and duration on ART. Results: Of the 582 PLHIV enrolled, the median age was 40 years (IQR: 34–46) and 54% were male. More than a fourth (25.8%) had multiple sexual partners and 11% had given oral sex. Median CD4 counts were 510 cells/mm3 (IQR: 338–700). The prevalence of hrHPV was 4.5% and lrHPV was 3.4%. Of those with hrHPV, 77% had HPV16. There were no significant associations with any predictors for both lrHPV and hrHPV in adjusted analyses. Conclusions: We found the prevalence of any oral HPV (hrHPV and lrHPV) to be 7.9% among PLHIV in India. Larger studies are required to better understand risk factors for oral HPV among Indian PLHIV.

Progression from human papillomavirus (HPV) infection to cervical lesion or clearance in women (18–25 years): Natural history study in the control arm subjects of AS04-HPV-16/18 vaccine efficacy study in China between 2008 and 2016

ABSTRACT Background Cervical cancer is the third most frequent cancer in Chinese women aged 15–44 years old. Human papillomavirus (HPV) is recognized as the main etiologic agent of cervical carcinomas. This study aims to better understand the natural history of HPV infections in Chinese women aged 18–25 years. Research Design and Methods Data from 3,025 control arm women (AS04-HPV-16/18 vaccine trial) were analyzed to assess the probability of progression or clearance from a 6-month persistent infection (6MPI) to a cervical intraepithelial neoplasia grade 2 or greater (CIN2+), and the association with clinical determinants. Data were analyzed using univariate and multivariable Cox models. Results A total of 1,324 women with 3,814 HPV infections were included, and 65.7% of the women had at least one 6MPI. Among those 6MPI, 5.0% progressed to CIN2+, while 61.0% cleared within 6 months. The risk of progression from 6MPI to CIN2+ was substantially higher for oncogenic versus non-oncogenic HPV types. Conclusions Oncogenic HPV infections showed lower clearance and higher risk to progress to CIN2 +. These findings observed in a population of Chinese women, confirmed previous findings from multinational studies. Trial Registration The PATRICIA and AS04-HPV-16/18 vaccine trials are registered at ClinicalTrials.gov (NCT00779766 and NCT00122681).

Ethiology and Pathophysiology of Whart Hpv Infection: A Review Article

Genital Human Papillomavirus (HPV) infection is a self-limiting and often asymptomatic disease. Genital HPV infection is divided into high-risk HPV (HPV 16 and 18) and low-risk HPV (HPV 6 and 11). Low-risk or non-oncogenic HPV produces a clinical picture of anogenital warts, which may be condylomatous, papules, or keratotic. The subclinical form of genital HPV infection can present with an "aceto-white" lesion found on the cervix that will appear when examined using an acetic acid solution evaluated by colposcopy. Based on the association with cervical cancer and precursor lesions, HPV can also be classified as high-risk (HR-HPV) and low-risk (LR-HPV) oncogenic types. LR-HPV types, such as HPV 6 and 11, can cause generalized genital warts or benign hyperproliferative lesions with a very limited predisposition to malignant progression, while infection with HR-HPV types, HPV 16 and 18, is associated with the development of pre-malignant and cervical lesions. Discussion: Human Papillomavirus is a small DNA virus (50-55nm) belonging to the family Papillomaviridae and genus Papillomavirus. Human papillomavirus (HPV) is a relatively small non-enveloped virus containing a double-stranded circular DNA genome associated with histone-like proteins and protected by a capsid formed by two final proteins, L1 and L2. Each capsid consists of 72 capsomeres, The pathogenesis of HPV begins with infection of stem cells in the basal layer of the epithelium. Once inside the cell, the virus requires expression of the E1 and E2 genes to maintain a low genome copy number. These proteins bind to the origin of replication and the virus secretes cellular DNA polymerases and other proteins required for DNA replication. In the suprabasal layer, the expression of genes E1, E2, E5, E6 and E7 contributes to the maintenance of the viral genome and induces cell proliferation, increasing the number of HPV-infected cells in the epithelium, resulting in a higher number of cells that will eventually produce infectious virions. Conclusion: In benign HPV lesions, cell proliferation increases leading to increased nutrition, resulting in competition for nutrients and oxygen. Both HR-HPV and LR-HPV E7 proteins increase the level of the transcription factor Hypoxia-inducible factor-1 (HIF-1), and induce increased expression of HIF-1 target genes under hypoxic conditions. Increased HIF-1 activity results in increased transcription of a subset of genes that support angiogenesis, and the induction of this angiogenesis is critical for the persistence and growth of HPV lesions such as genital warts.

The Prevalence of High- and Low-Risk Types of HPV in Patients with Squamous Cell Carcinoma of the Head and Neck, Patients with Chronic Tonsillitis, and Healthy Individuals Living in Poland.

Human papillomavirus (HPV) is a virus with the potential to infect human epithelial cells and an etiological agent of many types of cancer, including head and neck cancer. The aim of the study was to determine the prevalence of HPV infection in patients with head and neck squamous cell carcinoma (HNSCC), patients with chronic tonsillitis, and healthy individuals, and to establish high- and low-risk HPV genotypes in these groups. The objectives also comprised the delineation of the relationship between the infection with high- or low-risk HPV subtypes and clinicopathological and demographic characteristics of the study groups. This study was composed of 76 patients diagnosed with HNSCC, 71 patients with chronic tonsillitis, and 168 cases without either of these conditions (the control group). HPV detection and identification of subtypes were performed on isolated DNA using a test which allowed detection of 33 common high-risk and low-risk HPV subtypes. The prevalence of HPV infection was 42.1%, 25.4%, and 37.5% in HNSCC, chronic tonsillitis, and control groups, respectively. HPV 16 was the most prevalent genotype in all groups and the non-oncogenic HPV 43/44 was frequent in HNSCC patients. This analysis provides insight into the prevalence of oral oncogenic and non-oncogenic HPVs in patients with head and neck cancer, patients with chronic tonsillitis and healthy individuals, and leads to the conclusion that further investigations are warranted to examine a larger cohort of patients focusing on high- and low-risk HPV genotypes. Efforts should be focused on screening and prevention strategies, and therefore, it is important to introduce tools for effective detection of HPV genotypes. Furthermore, given the role of vaccines against oral HPV infection, our observations lead to the suggestion that HPV vaccination should be of considerable importance in public health strategies.

Giant Condyloma Acumina or Tumor of Buschke And Lowenstein During Pregnancy: About A Case at The University Hospital of Angré, Abidjan

We are reporting a rare case of giant condyloma diagnosed in a young woman with a full-term pregnancy. It is a benign tumor of viral origin that may constitute a dystocia of soft tissue during pregnancy. It is transmitted mainly by sexual transmission and the virus responsible is Human Papilloma Virus (HPV) of the types 6 and 11. It is a tumor whose benignity is related to the presence of non-oncogenic HPV. It is characterized by its recurrent and invasive evolutionary power enabling to classify it as a borderline tumor, which could explain its severity. It is a tumor that most often occurs in an immunocompromised area, but in our observation, retroviral serology was negative. The treatment is essentially surgical and must be early and radical. Its prevention is imperative, based on the treatment of acuminated condylomas and the fight against sexually transmitted diseases.

Clinical validation of full genotyping CLART\xae HPV4S assay on SurePath and ThinPrep collected screening samples according to the international guidelines for human papillomavirus test requirements for cervical screening

BackgroundTo ensure the highest quality of human papillomavirus (HPV) testing in primary cervical cancer screening, novel HPV assays must be evaluated in accordance with the international guidelines. Furthermore, HPV assay with genotyping capabilities are becoming increasingly important in triage of HPV positive women in primary HPV screening. Here we evaluate a full genotyping HPV assay intended for primary screening.MethodsThe CLART® HPV4S (CLART4S) assay is a newly developed full-genotyping assay detecting 14 oncogenic (16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66, 68) and two non-oncogenic HPV genotypes (6, 11). It was evaluated using SurePath and ThinPrep screening samples collected from the Danish and Swedish cervical cancer screening programs, respectively. For calculation of sensitivity, 81 SurePath and 80 ThinPrep samples with confirmed ≥CIN2 were assessed. For clinical specificity analysis, 1184 SurePath and 1169 ThinPrep samples from women with <CIN2 histology were assessed. Sensitivity and specificity of the CLART4S assay was compared to an established reference test; the MGP-PCR (Modified General Primers GP5+/6+ with genotyping using Luminex). Inter and intra laboratory reproducibility of the assay was assessed using 540 SurePath and 520 ThinPrep samples, respectively. The genotype concordance between CLART4S and MGP-PCR was also assessed.ResultsIn SurePath samples, the sensitivity of CLART4S was 0.90 (MGP-PCR =0.93) and the specificity was 0.91 (MGP-PCR = 0.91); In ThinPrep samples the sensitivity of CLART4S was 0.98 (MGP-PCR = 1.00) and specificity was 0.94 (MGP-PCR =0.87). The CLART4S was shown to be non-inferior to that of MGP-PCR for both sensitivity (p = 0.002; p = 0.01) and specificity (p = 0.01; p = 0.00) in SurePath and ThinPrep samples, respectively. Intra-laboratory reproducibility and inter-laboratory agreement was met for both media types. The individual genotype concordance between CLART4S and MGP-PCR was good agreement for almost all 14 HPV genotypes in both media types.ConclusionsThe CLART4S assay was proved non-inferior to the comparator assay MGP-PCR for both sensitivity and specificity using SurePath and ThinPrep cervical cancer screening samples from the Danish and Swedish screening programs, respectively. This is the first study to demonstrate clinical validation of a full-genotyping HPV assay conducted in parallel on both SurePath and ThinPrep collected samples.

Persistence of oncogenic and non-oncogenic human papillomavirus is associated with human immunodeficiency virus infection in Kenyan women.

Objectives:Cervical cancer is caused by persistent infection with oncogenic, or “high-risk” types of human papillomaviruses, and is the most common malignancy in Kenyan women. A longitudinal study was initiated to investigate factors associated with persistent human papillomavirus detection among HIV-infected and HIV-uninfected Kenyan women without evidence of cervical dysplasia.Methods:Demographic/behavioral data and cervical swabs were collected from HIV-uninfected women (n = 82) and HIV-infected women (n = 101) at enrollment and annually for 2 years. Human papillomavirus typing was performed on swabs (Roche Linear Array). Logistic regression models of human papillomavirus persistence were adjusted for demographic and behavioral characteristics.Results:HIV-infected women were older and less likely to be married and to own a home and had more lifetime sexual partners than HIV-uninfected women. All HIV-infected women were receiving anti-retroviral therapy at enrollment and had satisfactory CD4 cell counts and HIV viral loads. One- and two-year persistent human papillomavirus detection was significantly associated with HIV infection for any human papillomavirus, high-risk human papillomavirus, International Agency for the Research on Cancer-classified high-risk human papillomavirus, and non-oncogenic “low-risk” human papillomavirus.Conclusion:Persistent detection of oncogenic and non-oncogenic human papillomavirus was strongly associated with HIV infection in Kenyan women with re-constituted immune systems based on satisfactory CD4 cell counts. In addition to HIV infection, factors associated with an increased risk of human papillomavirus persistence included a higher number of lifetime sex partners. Factors associated with decreased risk of human papillomavirus persistence included older age and being married. Further studies are needed to identify the immunological defects in HIV-infected women that allow human papillomavirus persistence, even in women receiving effective anti-retroviral therapy. Further studies are also needed to determine the significance of low-risk human papillomavirus persistence in HIV-infected women.

Determinants of the presence of human papillomaviruses in the anal canal of Russian men.

Knowledge of determinants of anal human papillomavirus (HPV) infections among men is still limited as most of the studies are focused on high-risk populations and geographically narrowed. Such knowledge obtained in different populations is essential for better understanding of HPV natural history, transmission dynamics, and its role in the development and prevention of anogenital malignancies in different regions. Here we tested anal canal swab samples from 359 Russian heterosexual (323 human immunodeficiency virus [HIV]-negative and 27 HIV-positive, aged 18-67 years) men attending a sexually transmitted infection clinic36 HPV types using a proficient Luminex assay. HPV-positivity in anal samples was common for 332 HIV-negative heterosexual men for overall HPV (15.7%, n = 52), oncogenic HPV (9.6%, n = 32), nononcogenic HPV (8.1%, n = 27), and multiple HPV infections (4.5%, n = 14). The most common anal HPV types were HPV16 (5.7%), HPV45, and HPV51 (1.8% each), HPV66, and HPV87 (1.8% each). No association was found with the number of lifetime sexual partners, age of participants at the time of the study, or their sexual debut. Although anal HPV positivity was more common among HIV-positive men, the current study provides additional evidence that anal HPV can be frequently detected in heterosexual HIV-negative men favoringfurther studies on transmission routes to discriminate between contamination and true HPV infection.

Racial differences in the prevalence of oncogenic oral human papillomavirus infection types in the United States adult population.

The purpose of this study was to describe the prevalence of oral human papillomavirus (HPV) types according to race and to examine risk factors for oral HPV infection in United States adults. Using 2009-2014 data from the National Health and Nutrition Examination Survey, 13981 subjects were examined. Prevalence of oral HPV and individual oncogenic HPV types were described according to race. Multivariable logistic and linear regressions were used to examine the risk factors for infection and coinfection. Oncogenic and nononcogenic oral HPV infections were significantly more prevalent in black subjects. Infections with oral HPV types 16 and 51 were more prevalent in white subjects, whereas HPV types 35 and 58 were more prevalent in black subjects. We identified 4 oral HPV types that differ by race. Future research on HPV types (especially those that differ by race) may help elucidate their potential role in carcinogenesis and cancer disparities.

Determinants for Genital Human Papillomavirus (HPV) Infection in Tunisian Women with Normal Pap smear: Are There Different Risk Profiles for Oncogenic and Nononcogenic HPV Types?

Determinants for Genital Human Papillomavirus (HPV) Infection in Tunisian Women with Normal Pap smear: Are There Different Risk Profiles for Oncogenic and Nononcogenic HPV Types?

Cáncer de laringe y Virus del papiloma humano en adultos del Hospital Escuela Universitario, Honduras

El cáncer de laringe es el más frecuente en cabeza y cuello; recientemente se plantea la infección por virus del papiloma humano (VPH) en la carcinogénesis. El objetivo del estudio fue establecer la presencia del VPH en pacientes con carcinoma de laringe en el Hospital Escuela Universitario (HEU) desde marzo de 2012 a marzo de 2015.Se hizo un estudio retrospectivo. Previa autorización del Departamento de Patología se revisaron los diagnósticos histopatológicos de pacientes con carcinoma de laringe en HEU. El universo fue de 91 pacientes con carcinoma de laringe; la muestra fue de 30 pacientes.Se identificó el ADN del VPH mediante la reacción en cadena de la polimerasa (PCR) y genotipificación molecular utilizando sondas marcadas mediante hibridación reversa LIPA (INNO-LIPA HPV Genotyping Extra). Se realizó tabulación y análisis en EPIINFO 3.5.4; se obtuvo frecuencias, porcentajes, medidas de tendencia central y de significancia estadística.Los resultados indican distribución por género, masculino 26/30 (86.6 %) y femenino 4/30 (13.3 %); edad media para VPH negativos (62.7 años) y para VPH positivos (54.8 años). Procedentes del área rural 19/30(63.3 %). Cofactores predominantes: el tabaquismo en 22/30 (73.3 %) y alcoholismo 20/30 (66.6 %). El sitio anatómico más afectado fue la glotis 16/30(53.3 %). Histológicamente predominó el carcinoma epidermoide moderadamente diferenciado 21/30 (70 %). Al momento del diagnóstico12/ 30(40 %) se encontraban en estadio III.El porcentaje de VPH fue del 43.3 % (13/30), IC 95%(25.5-62.6), p&lt; 0.001. Se identificaron genotipos de alto riesgo (16, 31, 33, 51, 52, 53, 56, 58) y bajo riesgo (6, 11, 71 y 74), predominando VPH 11 (23 %) no oncogénico, seguido del VPH 16 (15.4 %) oncogénico. Hubo coinfección de dos o más genotipos.La conclusión es que el porcentaje de VPH fue del 43.3 % con predominio de VPH 11 y 16. Debido a la muestra reducida y a la variabilidad de los resultados en estudios internacionales, se recomiendan estudios futuros con casuística más grande.Revista Portal de la Ciencia, No.11, diciembre 2016, p.40-53

Dietary intake of selected nutrients and persistence of HPV infection in men.

Human papillomavirus (HPV) infection is a common sexually transmitted disease. Although often transitory, persistent oncogenic HPV infection may progress to a precursor lesion and, if not treated, can further increase the risk of cancer. The purpose of this study was to investigate the relation between dietary intake and HPV persistent infection in men of a Brazilian cohort. The study population consisted of 1,248 men from the Brazilian cohort of the HIM (HPV in Men) Study, ages 18 to 70 years, who completed a quantitative food frequency questionnaire. U Mann-Whitney test was used to assess differences in median nutrient intake of selected nutrients. The association of dietary intake and persistent HPV infection was assessed in multivariate logistic models. The prevalence of any HPV infection at baseline was 66.6%. Of 1,248 participants analyzed, 1,211 (97.0%) were HPV positive at one or more times during the 4 years of follow-up and 781 (62.6%) were persistently HPV positive. Men with nonpersistent oncogenic HPV infections had higher median intake of retinol (p = 0.008), vitamin A (p < 0.001) and folate (DFE; p = 0.003) and lower median intake of energy (p = 0.005) and lycopene (p = 0.008) in comparison to men with persistent oncogenic infections. No significant association was found between selected nutrients and persistent oncogenic HPV infection. For nononcogenic persistent infections, only vitamin B12 intake was significantly associated (p = 0.003, test for trend). No association was observed between dietary intake and persistent oncogenic-type HPV infection; however, vitamin B12 intake was inversely associated with nononcogenic HPV persistence.

Human papillomavirus prevalence and associated factors in women and men in south China: a population-based study

Oncogenic human papillomavirus (HPV) infection is a cause of many anogenital cancers in women and men; however, there is little research on HPV prevalence and risk factors that includes both women and men from the same population. A total of 4687 participants, including 2378 women and 2309 men aged 18–55 years old from the same community, were enrolled in the study in Liuzhou, China. Exfoliated cells were collected from the participants from different anatomic sites and were tested for 13 oncogenic and 3 non-oncogenic HPV types. The prevalence of any oncogenic HPV type was higher in women than in men (18.7% vs 9.4%, P<0.001), whereas the prevalence of HPV 6 and 11 infection was similar (1.4% vs 1.2%, P=0.6832). HPV 52, 58, 16, 39 and 18 were the five most prevalent types in both sexes. Sexual and hygienic behaviors were associated with HPV infection in both women and men. We found that oncogenic HPV DNA detection is more prevalent in women than in men in China, whereas the prevalence of HPV 6 and 11 is similar in both sexes. The data indicate that the interaction of host and virus might be different among high- and low-risk HPV types.

Prevalence, incidence, clearance, and associated factors of genital human papillomavirus infection among men: a population-based cohort study in rural China.

The natural history of human papillomavirus (HPV) infection in men on a population base has rarely been studied in general, particularly among Chinese men. A total of 1,286 men ages 25 to 65 years from rural China were enrolled during 2009-2010 and their genital HPV infection status was assessed biannually for up to seven visits using PCR and sequencing methods. Prevalence analysis was performed among men with at least one valid HPV result (N = 1,279) and men with at least two consecutive HPV results (N = 1,059) were included in incidence and clearance analyses (median follow-up time, 31.8 months; interquartile range, 15.4-37.9 months). The prevalence and incidence of any HPV type, oncogenic, and nononcogenic HPV were 17.8%, 6.4%, 12.4%, and 14.6, 4.9, 10.8 per 1,000 person months, respectively. The median duration of infection with any HPV type, oncogenic, and nononcogenic HPV was 11.5, 6.8, and 11.5 months, respectively. The number of lifetime sexual partners was consistently associated with increased risk of prevalent and incident infection of HPV. Men ages 25 to 50 years had a higher incidence and longer duration of HPV infection than older men (51-65 years). This epidemiologic investigation provides basic information of genital HPV infection among the Chinese male population; these data are crucial for the consideration of primary strategies against HPV-related carcinoma in the Chinese male and female population.

Uncommon non-oncogenic HPV genotypes, TP53 and MDM2 genes polymorphisms in HIV-infected women in Southern Brazil

BackgroundIt is believed that Human Papillomavirus (HPV) and Human Immunodeficiency Virus coinfection contributes to increase the risk for cervical intraepithelial injuries. Several factors may contribute to cervical cancer (CC) development, including genetic variants such as TP53 and MDM2 gene polymorphisms. Materials and methodsA hundred HIV-infected women were examined for HPV detection and its genotypes, as well as the frequencies of the SNPs Arg72Pro and SNP309 and their associations with CC risk factors. Nested Polymerase Chain Reaction (nPCR) was used for HPV detection and PCR-RFLP for TP53 and MDM2 SNP309 genotyping. ResultsHPV DNA was detected in 68% of samples. A higher frequency of low-risk HPV genotypes (66.7%) was observed when compared to high-risk genotypes (33.3%). Nine different HPV genotypes were identified, with the highest prevalence of HPV-6, followed by HPV-16 and 31. p53 Arg72Arg and SNP309 TG genotype were the most prevalent. HPV genotyping was performed by sequencing. ConclusionThe data obtained suggest that HIV-infected women are more susceptible to be infected by low-risk HPV (LR-HPV) genotypes than by high-risk (HR-HPV), and Pro72Pro of TP53 gene and TG of MDM2 SNP309 genotypes apparently seem to be protective factors among HIV-infected women for HPV acquisition and HR-HPV infection, respectively, in a sample of Southern Brazilian woman. Future investigations in larger populations are necessary to better understand the potential roles of these SNPs and the behavior of non-oncogenic HPV genotypes in HIV-mediated immunosuppression cases.

HPV vaccines to prevent cervical cancer and genital warts: an update

Cervical cancer is an important public health problem worldwide, and especially in developing countries. The link between cervical cancer and oncogenic human papillomavirus (HPV) infection has been clearly established. Furthermore, non-oncogenic HPV are responsible for the majority of genital warts. Two prophylactic HPV vaccines are available, which have the potential of considerably reducing HPV-related morbidity and mortality. Both vaccines are based on virus-like particles of the L1 capsid protein, and are highly efficacious and immunogenic if given before exposure to HPV, i.e. to adolescent girls between 9 and 13 years of age in a three-dose schedule. This review describes the immunology of natural HPV infections and the immune response evoked through vaccination. The current duration of protection is 8.4 years with the bivalent vaccine (HPV16/18) and 5 years with the quadrivalent vaccine (HPV6/11/16/18). Research is on-going to evaluate the efficacy of the current vaccines in a two-dose schedule, as compared to the recommended three-dose schedule. To increase the protection, the development and testing of a nine-valent prophylactic HPV vaccine (HPV6/11/16/18/31/33/45/52/58) is being undertaken. Research is also directed towards therapeutic vaccines and the development of a prophylactic L2 vaccine.

Single human papillomavirus 16 or 52 infection and later cytological findings in Japanese women with NILM or ASC-US

The relationship between oncogenic human papillomavirus (HPV) infection and later cytological findings in the uterine cervix is unknown in women who were negative for intraepithelial lesion and malignancy (NILM) or atypical squamous cells of undetermined significance (ASC-US). This was investigated in this study in a Japanese population to determine the clinical utility of oncogenic (HPV) genotyping. The relative risk of progressive cytological findings 2 years after identification of oncogenic HPV infection was higher than in cases of non-oncogenic HPV infection (relative risk 3.827; 95% confidence interval (CI): 1.282-11.422), as well as in cases of negative HPV infection (relative risk 2.124; 95% CI: 1.451-3.110). Moreover, the relative risk of progression of cytological findings 2 years later in cases of HPV-16 infection was higher than in cases of HPV-52 infection (relative risk 2.094; 95% CI: 1.005-3.935). Therefore, the initial HPV-DNA genotype may be a potential predictive marker of later progression of cytological findings in the uterine cervix in cases of NILM or ASC-US.

Understanding genital warts: epidemiology, pathogenesis, and burden of disease of human papillomavirus.

As the most commonly sexually transmitted disease worldwide, human papillomavirus (HPV) infections are associated with significant morbidity and mortality. HPV infections most commonly affect young adults, women under 25 in particular. The most common risk factor for HPV infection in both sexes is a high number of lifetime sexual partners, whereas leading protective factors include circumcision, consistent condom use, and abstinence. Over 100 HPV types have been identified to date and are classified according to their level of oncogenic potential. HPV types 6 and 11 are responsible for approximately 90% of genital warts; HPV types 16 and 18 are responsible for 70% of invasive cervical cancers. External genital warts (EGWs) are the most common clinical manifestation of nononcogenic HPV infection. Coinfection with multiple HPV types is possible and may combine both low- and high-risk types, even in cases of genital warts. HPV infections are DNA viruses transmitted through skin-to-skin contact, invading the basal epithelial cells via microtears and evading the host immune response. Although non-life threatening, even low-risk HPV-type infections such as EGW carry a substantial psychosocial and economic burden. Stressors include the shame and embarrassment related to diagnosis, as well as the inconvenience and discomfort of treatment and the fear of recurrence, transmission, and the possible threat of cancer. Costs relate to routine screening for cervical cancer, treatment of genital warts, and the management and follow-up of malignancies.

A prospective analysis of smoking and human papillomavirus infection among men in the HPV in Men Study

At present it is unknown whether the higher prevalence of human papillomavirus (HPV) infection among smokers in men is attributed to a higher probability of acquiring an infection or because of longer infection persistence. Thus, we investigated the role of smoking on the incidence (acquisition) and clearance (persistence) of genital HPV infections among 4,026 men in the HPV in Men (HIM) Study, a multinational prospective study of the natural history of genital HPV infection in men. Genital HPV infections were grouped by any, oncogenic and nononcogenic HPV infections and smoking status was categorized as current, former and never smokers. The incidence of any, oncogenic and nononcogenic HPV infections was significantly higher among current smokers compared to former and never smokers (p < 0.01). In multivariable analyses adjusting for sexual behavior and potential confounders, when compared to never smokers, current smokers exhibited significantly higher probability of acquiring any [hazard ratio (HR) = 1.23; 95% confidence interval (CI) 1.02-1.50] and nononcogenic (HR = 1.21; 95% CI 1.00-1.45) infections and a borderline significant probability for oncogenic infections (HR = 1.18; 95% CI 0.98-1.41). Although the median duration of HPV infection was generally longer among current smokers, we found no statistically significant associations in the multivariable analyses. Overall, these results demonstrated that current smoking exhibited the highest incidence and highest probability of acquiring genital HPV infections.