Nononcogenic Human Papillomavirus Infections Research Articles

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.

Racial Differences in the Incidence and Clearance of Human Papilloma Virus (HPV): The HPV in Men (HIM) Study

This analysis assessed the acquisition (incidence) and persistence (clearance) of human papilloma virus (HPV) infection by self-reported race among men in The HPV in Men (HIM) Study, a multinational prospective study of the natural history of genital HPV infections. Self-reported race was categorized as White, Black, Asian/Pacific Islander (PI), or multiple and mixed race. Genital samples were combined for HPV DNA testing and categorized by any, oncogenic, and non-oncogenic HPV infections. Asian/PI race had significantly the lowest incidence of any, oncogenic, and non-oncogenic HPV infection (P < 0.001). In multivariable analyses, Asian/PI race was associated with a lower probability of acquiring any [HR = 0.63; 95% confidence interval (CI), 0.42-0.95] and non-oncogenic HPV infection (HR = 0.61; 95% CI, 0.40-0.93) when compared to Whites. No significant associations were evident for Asian/PI race for clearance. Multiple and mixed race was significantly associated with lower probability of acquiring non-oncogenic HPV infection (HR = 0.83; 95% CI, 0.69-0.99) and borderline significant associations were observed for any HPV (HR = 0.91) and oncogenic infections (HR = 0.92). Multiple and mixed race was associated with a lower probability of clearing any (HR = 0.92; 95% CI, 0.84-1.00) and oncogenic HPV infections (HR = 0.85; 95% CI, 0.75-0.95). Asian/PI race had the lowest incidence of HPV and exhibited a lower probability of acquiring new HPV infections. Multiple and mixed race had the second lowest incidence of infection and was associated with a lower probability of acquiring and clearing an HPV infection. Race-specific differences in HPV infection could be due to behavior, innate genetic differences, or circulating intratypic HPV variants.

Incidence and clearance of oral human papillomavirus infection in men: the HIM cohort study

Oral human papillomavirus (HPV) infection causes a subset of oropharyngeal cancers. These cancers disproportionately affect men, are increasing in incidence, and have no proven prevention methods. We aimed to establish the natural history of oral HPV infection in men. To estimate incidence and clearance of HPV infections, men residing in Brazil, Mexico, and the USA who were HIV negative and reported no history of anogenital cancer were recruited into the HPV Infection in Men (HIM) cohort study. A subset of the cohort who provided two or more oral rinse-and-gargle samples with valid HPV results and who completed a minimum of 2 weeks of follow-up were included in this analysis. Oral rinse-and-gargle samples and questionnaire data were obtained every 6 months for up to 4 years. Samples were analysed for the presence of oncogenic and non-oncogenic HPV infections by the linear array method. 1626 men aged 18-73 years and with a median follow-up of 12·7 months (IQR 12·1-14·7) were included in the analysis. During the first 12 months of follow-up, 4·4% (95% CI 3·5-5·6; n=115 incident infections) of men acquired an incident oral HPV infection, 1·7% (1·2-2·5; n=53 incident infections) an oral oncogenic HPV infection, and 0·6% (0·3-1·1; n=18 incident infections) an oral HPV 16 infection. Acquisition of oral oncogenic HPV was significantly associated with smoking and not being married or cohabiting, but was similar across countries, age groups, and reported sexual behaviours. Median duration of infection was 6·9 months (95 % CI 6·2-9·3; n=45 cleared infections) for any HPV, 6·3 months (6·0-9·9; n=18 cleared infections) for oncogenic HPV, and 7·3 months (6·0-not estimable; n=5 cleared infections) for HPV 16. Eight of the 18 incident oral HPV 16 infections persisted for two or more study visits. Newly acquired oral oncogenic HPV infections in healthy men were rare and most were cleared within 1 year. Additional studies into the natural history of HPV are needed to inform development of infection-related prevention efforts. US National Cancer Institute, Merck Sharp & Dohme.

Smoking and Human Papillomavirus (HPV) Infection in the HPV in Men (HIM) Study

The influence of smoking on the natural history of HPV infection in men is not well understood. Smoking could influence the incidence and persistence of HPV infections by suppressing local immune function, increased cellular proliferation, upregulated proinflammatory factors, or induced host DNA damage resulting in increased susceptibility to infection. The purpose of this analysis is to assess prevalent HPV infections by smoking status in men, and to determine baseline risk of HPV infection associated with smoking. The HPV in Men (HIM) study is a multinational prospective study of the natural history of HPV infections in men. Samples from the coronal sulcus, glans penis, shaft, and scrotum were combined for HPV DNA testing. Multivariable logistic regression was used to assess the association between smoking and any-, oncogenic-, and nononcogenic HPV infections. Our analyses revealed that current smoking was associated with an increased risk of any HPV infection (OR = 1.19; 95% CI: 1.01-1.41) and oncogenic HPV infection (OR = 1.24; 95% CI: 1.05-1.47). However, the association between smoking and any HPV infection (OR = 1.35; 95% CI: 1.05-1.73) and oncogenic HPV infection (OR = 1.46; 95% CI: 1.11-1.92) was only evident among men reporting fewer lifetime sexual partners. These results suggest that current smokers with the fewest number of sexual partners are associated with an increased risk for oncogenic HPV infection. The relationship between smoking and HPV infection remains understudied in men; these data shed new light on the interplay between smoking, sexual activity, and risk of HPV infection.

HPV Vaccination to Prevent HIV Infection: Time for Randomized Controlled Trials

Despite many years of rigorous evaluation of a variety of interventions, HIV incidence rates in parts of Africa remain unacceptably high. A recent review identified 37 randomized controlled trials testing interventions to reduce HIV incidence.1 Except for 3 randomized controlled trials of male circumcision2‐4 and 1 trial of syndromic treatment of sexually transmitted diseases,5 and, recently, 1 trial of a vaginal microbicide,6 no significant reductions in HIV incidence were observed. In some trials of vaginal microbicides, trial participants in the active treatment arm actually had increased HIV incidence rates.7 Trials with candidate vaccines have been equally disappointing.8 A recently completed trial of a prime-boost strategy conducted in Thailand showed statistically significant, but limited, protection against HIV.9 Nevertheless, even vaccine optimists think that a preventive HIV vaccine is many years away. Sexually transmitted infections (STIs) were identified as important cofactors for HIV transmission early in the epidemic.10,11 Many prospective observational studies showed that the presence of ulcerative and nonulcerative STIs increased the likelihood of HIV transmission.10,11 Several interventions were based on this observation including mass treatment with antibiotics,12 improved syndromic management of STIs,5,13 and herpes simplex virus (HSV)-2 suppressive treatment.14 Null findings of these interventions should be interpreted with caution. Failure to show an effect does not necessarily mean that the STI is not causally associated with HIV. As Barnabas and Wasserheit highlight,15 the stage of the HIV epidemic in which an intervention trial is conducted may significantly influence observed efficacy. Another possible reason for the failure of these trials to demonstrate efficacy is that the intervention may not have adequately controlled the STI or its biologic effects.

Factors Associated with Acquisition and Clearance of Human Papillomavirus Infection in a Cohort of US Men: A Prospective Study

Our understanding of factors associated with acquisition and clearance of human papillomavirus (HPV) in men has been limited. This study sought to determine factors associated with those aspects of HPV infection in a cohort of US men. A total of 285 men aged 18-44 years were monitored every 6 months for approximately 18 months. Risk-factor information was obtained at each visit by use of a self-administered questionnaire. A continuous-time 2-state Markov model was applied. Lifetime number of sex partners reported at enrollment was the most significant risk factor for acquisition of all types of HPV. Men reporting >16 lifetime sex partners were at significantly elevated risk of any HPV infection (adjusted hazard ratio [AHR], 2.8 [95% confidence interval {CI}, 1.1-7.1]), oncogenic HPV infection (AHR, 9.6 [95% CI, 2.4-37.8]), and nononcogenic HPV infection (AHR, 3.6 [95% CI, 1.3-9.9]), compared with those reporting 0-4 partners. Circumcised men were 3 and 6 times more likely to clear infection with any and oncogenic HPV types, respectively. In addition, having had >16 lifetime sex partners was associated with greater likelihood of clearance of oncogenic HPV infection (AHR, 4.9 [95% CI, 1.2-19.8]). The key factor associated with acquisition of HPV was lifetime number of sex partners, whereas circumcision was the most significant determinant for clearance of any HPV infection and oncogenic HPV infection.

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Circumcision and sexual behavior: Factors independently associated with human papillomavirus detection among men in the HIM study

There is growing interest in understanding human papillomavirus (HPV) infection and related disease among men. To date there have been numerous studies reporting HPV DNA prevalence among men from several different countries, however, few have incorporated multivariable analyses to determine factors independently associated with male HPV detection. The purpose of this study was to assess the factors independently associated with HPV detection in men ages 18-70 years residing in Brazil (n = 343), Mexico (n = 312), and the United States (US) (n = 333). In samples combined from the coronal sulcus, glans penis, shaft, and scrotum, we evaluated factors associated with any, oncogenic, and nononcogenic HPV infections. In multivariable analyses, detection of any HPV infection was significantly associated with reported race of Asian/Pacific Islander, lifetime and recent number of sexual partners, and having sex in the past 3 months. Oncogenic HPV detection was independently associated with lifetime and recent number of sexual partners, and having sex in the past 3 months. NonOncogenic HPV infection was independently associated with lifetime number of sexual partners. Circumcision, assessed by clinical examination, was associated with reduced risk of HPV detection across all categories of HPV evaluated. HPV detection in men in the current study was strongly related to sexual behavior and circumcision status. Interventions such as circumcision may provide a low-cost method to reduce HPV infection.

Age‐Specific Prevalence, Incidence, and Duration of Human Papillomavirus Infections in a Cohort of 290 US Men

Human papillomavirus (HPV) infections cause disease in men and women, and male-to-female HPV transmission influences the risk of cancer in females. The purpose of the present study was to describe the overall and age-specific incidence and clearance of HPV infections in men. In a prospective cohort study of 290 men aged 18-44 years, participants were examined at baseline and every 6 months, with a mean duration of follow-up of 15.5 months. The period prevalence was 52.8% for any, 31.7% for oncogenic, and 30.0% for nononcogenic HPV infection. The 12-month cumulative risk of acquiring a new HPV infection was 29.2%. Incidences of HPV types 6, 11, 16, and 18 were 2.8, 0.5, 4.8, and 0.8 per 1000 person-months, respectively. The median time to clearance of any HPV infection was 5.9 months (95% confidence interval, 5.7-6.1 months), with comparable times to clearance for oncogenic and nononcogenic infections. Approximately 75% of men tested negative for any HPV 12 months after initial HPV detection. Age was not significantly associated with HPV incidence or duration of infection in men. HPV infection in men was common, with relatively rapid rates of acquisition and clearance.

Human papillomavirus prevalence at the USA–Mexico border among women 40 years of age and older

The incidence of cervical cancer increases with age among USA Hispanics and women living in Latin America starting in the fourth decade of life. We conducted a study of women > or = 40 living at the USA-Mexico border to determine the prevalence and risk factors for human papillomavirus (HPV) infection detected by polymerase chain reaction. In all, 9.2% of participants tested HPV positive. Compared with women aged 50-59, odds ratios of 8.82 and 6.67 were observed for women > or = 60 and 40-49, respectively. Among women aged 40-49, both oncogenic and non-oncogenic HPV infections were detected; however, women > or = 60 were positive for predominantly oncogenic genotypes. HPV risk significantly increased with > or = 2 lifetime sexual partners in adjusted models. These data suggest that the prevalence of HPV infection may have a second peak among post-menopausal Hispanic women.

Epidemiology of acquisition and clearance of cervical human papillomavirus infection in women from a high-risk area for cervical cancer.

Acquisition and clearance of cervical human papillomavirus (HPV) infection were analyzed among 1425 low-income women attending a maternal and child health program in São Paulo, Brazil. Specimens collected every 4 months were tested by a polymerase chain reaction protocol (MY09/11). In all, 357 subjects were positive at least once. There were 1.3% new infections per month, with 38% cumulative positivity after 18 months. Of 177 positive subjects at enrollment, only 35% remained infected after 12 months. The monthly clearance rate was higher for nononcogenic types (12.2%; 95% confidence interval [CI], 9.6-15.4) than for oncogenic HPV infections (9.5%; 95% CI, 7.5-11.9). Median retention times were 8.1 months (95% CI, 7.8-8.3) for oncogenic types and 4.8 months (95% CI, 3.9-5.6) for nononcogenic HPV infections. The mean infection durations were 8.2 and 13.5 months for nononcogenic and oncogenic types, respectively. Although a woman's age did not affect mean duration for oncogenic types (13-14 months), nononcogenic-type infections lasted longer (10. 2 months) among younger (<35 years old) than in older women (5.6 months).