Explore the vast range of titles available.

► Development of CIN3 is rare in women aged 30 years who test HPV DNA-negative. ► Heterosexual transmission is extremely common. ► Transmission between the anus and cervix and vice versa are common in a woman. ► Prevalence of penile HPV is greater than cervical HPV but persistence is less likely. ► Persons with HIV, MSM, and women with cervical cancer are at risk for anal cancer. This chapter addresses the natural history of anogenital human papillomavirus (HPV) infection. Cervical infections are the best understood HPV infection. Cervical HPV persistence is the known necessary event for the development of cervical cancer. New infections appearing at any age are benign unless they persist. Several long-term natural history studies have now shed light on the very low risk of cervical intraepithelial neoplasia (CIN) 3+ in women past the peak of HPV acquisition (e.g., 30 or older) who are HPV-negative or clear their HPV. Although data on transmission of HPV are finally emerging, rates of transmission between heterosexual couples vary widely among studies. Factors that affect the calculations of these rates include a) intervals between testing points, b) rates of concordance or discordance at baseline, and c) difficulty in defining established infections versus contamination. Both cervix to anus and anus to cervix autoinoculation in the same woman appears to be quite common. Whether either site serves as a long-term reservoir is unknown. Studies show that anal infections in women and in men who have sex with men are quite common with cumulative rates up to 70–90%. Similarly, clearance of anal HPV is also common, with few individuals showing persistence unless they are human immunodeficiency virus (HIV)-infected. HIV strongly influences the development of anal intraepithelial neoplasia (AIN). The few studies on the natural history of AIN in HIV-infected men suggest that high-grade AIN is a precursor to invasive anal cancer. Although no natural history studies of AIN are available in women, women with other HPV-associated lesions, including CIN3+ and vulvar cancer, have higher rates of anal cancer. Data on the natural history of HPV of the male genitalia are also emerging, although penile intraepithelial neoplasia is poorly understood. Cumulative rates of HPV are extremely high in men and risks are associated with sexual behavior. Unlike women, prevalence rates are steady across all ages, suggesting that men do not develop protection against reinfection. This article forms part of a special supplement entitled “Comprehensive Control of HPV Infections and Related Diseases” Vaccine Volume 30, Supplement 5, 2012.

Human papillomaviruses (HPVs) cause genital warts and cancers in men. The natural history of HPV infection in men is largely unknown, and that information is needed to inform prevention strategies. The goal in this study was to estimate incidence and clearance of type-specific genital HPV infection in men, and to assess the associated factors. Men (aged 18–70 years), residing in Brazil, Mexico, and the USA, who were HIV negative and reported no history of cancer were recruited from the general population, universities, and organised health-care systems. They were assessed every 6 months for a median follow-up of 27·5 months (18·0–31·2). Specimens from the coronal sulcus, glans penis, shaft, and scrotum were obtained for the assessment of the status of HPV genotypes. In 1159 men, the incidence of a new genital HPV infection was 38·4 per 1000 person months (95% CI 34·3–43·0). Oncogenic HPV infection was significantly associated with having a high number of lifetime female sexual partners (hazard ratio 2·40, 1·38–4·18, for at least 50 partners vs not more than one partner), and number of male anal-sexual partners (2·57, 1·46–4·49, for at least three male partners vs no recent partners). Median duration of HPV infection was 7·52 months (6·80–8·61) for any HPV and 12·19 months (7·16–18·17) for HPV 16. Clearance of oncogenic HPV infection decreased in men with a high number of lifetime female partners (0·49, 0·31–0·76, for at least 50 female partners vs not more than one partner), and in men in Brazil (0·71, 0·56–0·91) and Mexico (0·73, 0·57–0·94) compared with the USA. Clearance of oncogenic HPV was more rapid with increasing age (1·02, 1·01–1·03). The data from this study are useful for the development of realistic cost-effectiveness models for male HPV vaccination internationally. National Cancer Institute.

Background We conducted a systematic review and meta-analysis to assess efficacy and safety of prophylactic HPV vaccines against cervical cancer precursor events in women. Methods Randomized-controlled trials of HPV vaccines were identified from MEDLINE, Cochrane Central Register of Controlled Trials, conference abstracts and references of identified studies, and assessed by two independent reviewers. Efficacy data were synthesized using fixed-effect models, and evaluated for heterogeneity using I 2 statistic. Results Seven unique trials enrolling 44,142 females were included. The fixed-effect Relative Risk (RR) and 95% confidence intervals were 0.04 (0.01-0.11) and 0.10 (0.03-0.38) for HPV-16 and HPV 18-related CIN2+ in the per-protocol populations (PPP). The corresponding RR was 0.47 (0.36-0.61) and 0.16 (0.08-0.34) in the intention-to-treat populations (ITT). Efficacy against CIN1+ was similar in scale in favor of vaccine. Overall vaccines were highly efficacious against 6-month persistent infection with HPV 16 and 18, both in the PPP cohort (RR: 0.06 [0.04-0.09] and 0.05 [0.03-0.09], respectively), and the ITT cohorts (RR: 0.15 [0.10-0.23] and 0.24 [0.14-0.42], respectively). There was limited prophylactic effect against CIN2+ and 6-month persistent infections associated with non-vaccine oncogenic HPV types. The risk of serious adverse events (RR: 1.00, 0.91-1.09) or vaccine-related serious adverse events (RR: 1.82; 0.79-4.20) did not differ significantly between vaccine and control groups. Data on abnormal pregnancy outcomes were underreported. Conclusions Prophylactic HPV vaccines are safe, well tolerated, and highly efficacious in preventing persistent infections and cervical diseases associated with vaccine-HPV types among young females. However, long-term efficacy and safety needs to be addressed in future trials.

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.

Limited data on the efficacy of the quadrivalent HPV vaccine are available for males. In this trial involving 4065 healthy boys and young men 16 to 26 years of age, the quadrivalent vaccine against HPV reduced the occurrence of external genital lesions by 60%. Human papillomavirus (hpv) infects the squamous epithelium in both sexes, leading to anogenital condylomata acuminata and, in males, to cancers of the penis, anus, and oropharynx. 1 The rate of genital HPV infection among males is similar to that in females. In any 12-month period, the probability that a sexually active male will acquire a new genital HPV infection is 0.29 to 0.39, 2 – 4 which is similar to estimates for females. However, there are differences between the sexes in the immune response to HPV. A larger proportion of females are HPV-seropositive (17.9%, vs. 7.9% of males), and females . . .

Infection with human papillomavirus (HPV) serotypes 16 and 18 in men who have sex with men is a cause of considerable morbidity associated with anal intraepithelial neoplasia. This study shows that the HPV vaccine decreases the risk of HPV-associated anal disease. Anal cancer is biologically similar to cervical cancer, including having a causal relationship with human papillomavirus (HPV) infection. 1 Although HPV type 6 (HPV-6) or HPV type 11 (HPV-11) alone is rarely causal, the proportion of anal cancers associated with infection with HPV type 16 (HPV-16) or HPV type 18 (HPV-18) is as high as or higher than the proportion of cervical cancers. 1 Just as cervical cancer is preceded by high-grade cervical intraepithelial neoplasia (grade ≥2), anal cancer is preceded by high-grade anal intraepithelial neoplasia (grade 2 or 3). 2 – 4 Although not yet formally demonstrated, prevention or treatment of high-grade anal . . .

There is limited understanding of epidemiology and time trends of human papilloma virus (HPV)‐driven head and neck cancers (HNC) in Japan, especially outside of the oropharynx. To assess HPV‐driven HNC, a non‐interventional study (BROADEN) of HNC patients diagnosed in 2008–2009 and 2018–2019 was conducted in Japan. Adult patients with oropharyngeal, nasopharyngeal, laryngeal, hypopharyngeal or oral cavity cancers were included in this study. HPV was centrally tested using p16INK4a immunohistochemistry, HPV‐DNA PCR and HPV E6*I mRNA. HPV attributability required positivity in at least two tests (p16INK4a immunohistochemistry, HPV‐DNA PCR, HPV E6*I mRNA) in the oropharynx, and HPV‐DNA and HPV E6*I mRNA positivity for non‐oropharynx sites. Nineteen hospitals included a total of 1108 patients, of whom 981 had valid samples. Men accounted for 82% of HNC diagnoses. Patients in the earlier cohort were younger and included a higher percentage of smokers. There was an increasing trend of HPV‐driven oropharyngeal cancer over the last decade, from 44.2% to 51.7%. HPV attribution in nasopharyngeal cancers was 3.2% in 2008–2009 and 7.5% in 2018–2019; and 4.4% and 0% for larynx respectively. In total, 95.2% of HPV‐driven HNC were attributed to HPV genotypes included in the 9‐valent HPV vaccine being HPV16 the most prominent genotype. These results suggest that an epidemiologic shift is happening in Japan, with a decrease in smoking and alcohol use and an increase in HPV‐driven HNC. The increasing trend of HPV‐driven HNC in Japan highlights the need for preventive strategies to mitigate the rise of HPV‐driven HNC. The BROADEN study is one of the largest observational studies conducted in Japan assessing human papilloma virus (HPV) in head and neck cancer (HNC). The study includes 1108 patients diagnosed in 2008–2009 and 2018–2019 across 19 hospitals. Overall 981 HNC samples were tested by HPV‐DNA PCR, p16INK4a, and HPV E6*I mRNA in a central laboratory using strict quality control processes for all laboratory steps. This study demonstrates an increasing trend of HPV attributability in oropharyngeal cancer over this 10‐year period, from 44.2% in 2008–2009 to 51.7% in 2018–2019 reflecting an annual percentage change (APC) of 1.58%, as well as in nasopharyngeal cancers from 3.2% to 7.5% representing an APC of 8.92%. Men accounted for 82% of HNC diagnoses, and patients in the earlier cohort were younger and had a higher percentage of smokers. Notably, the study found that 94.6% of these HPV‐driven HNC cases were attributed to HPV genotypes included in the prophylactic 9‐valent HPV vaccine highlighting the value of potential preventive strategies.

BackgroundHuman papillomavirus (HPV) infection is estimated to be the most common sexually transmitted infection; an estimated 6.2 million persons are newly infected every year in the United States. There are limited data on HPV infection in heterosexual men MethodsWe conducted a systematic review of the literature by searching MEDLINE using the terms “human papillomavirus,” “HPV,” “male,” “seroprevalence,” and “serology” to retrieve articles published from 1 January 1990 to 1 February 2006. We included studies that had data on population characteristics and that evaluated male genital anatomic sites or specimens for HPV DNA or included assessments of seropositivity to HPV type 6, 11, 16, or 18 in men. We excluded studies that had been conducted only in children or immunocompromised persons (HIV infected, transplant recipients, or elderly) ResultsWe included a total of 40 publications on HPV DNA detection and risk factors for HPV in men; 27 evaluated multiple anatomic sites or specimens, 10 evaluated a single site or specimen, and 3 evaluated risk factors or optimal anatomic sites/specimens for HPV detection. Twelve studies assessed site- or specimen-specific HPV DNA detection. HPV prevalence in men was 1.3%–72.9% in studies in which multiple anatomic sites or specimens were evaluated; 15 (56%) of these studies reported ⩾20% HPV prevalence. HPV prevalence varied on the basis of sampling, processing methods, and the anatomic site(s) or specimen(s) sampled. We included 15 publications reporting HPV seroprevalence. Rates of seropositivity depended on the population, HPV type, and methods used. In 9 studies that evaluated both men and women, all but 1 demonstrated that HPV seroprevalence was lower in men than in women ConclusionHPV infection is highly prevalent in sexually active men and can be detected by use of a variety of specimens and methods. There have been few natural-history studies and no transmission studies of HPV in men. The information that we have reviewed may be useful for future natural-history studies and for modeling the potential impact of a prophylactic HPV vaccine

In response to the growing burden of HPV-associated oropharyngeal cancer, this study investigated clearance of oral HPV, the obligate precursor, in a longitudinal cohort of men from the US, Brazil, and Mexico. Oral gargles collected every 6 months from the HPV Infection in Men Study were HPV genotyped using SPF 10 PCR-DEIA-LiPA 25 . Oral HPV infection clearance and associated factors were assessed using Kaplan-Meier curves and Cox proportional hazards models, respectively. Median follow-up was 44.8 months with 403 and 186 men with an incident and prevalent oral HPV infection, respectively; and lower probability of clearance observed in prevalent infections. Infections were less likely to clear in the presence of increased sexual behaviors; and among prevalent infections, older men were less likely to clear their infection. Here, we report differences in prevalently and incidently detected infections with sexual behavior as a key factor and older age as a potential factor associated with clearance. Human papillomavirus (HPV)-associated oropharyngeal cancer is increasing but the natural history of oral HPV infection is not well understood. Here, the authors investigate clearance of oncogenic oral HPV infection in a cohort of men from the US, Brazil, and Mexico.

Worldwide human papillomavirus (HPV) prevalence in women with normal cytology at any given point in time is approximately 10% indicating that HPV is one of the most common sexually transmitted infections. HPV-16 is consistently the most common type and HPV-18 the second with some minor regional differences. Furthermore, across the spectrum of cervical lesions, HPV-16 is consistently the most common HPV type contributing to 50–55% of invasive cervical cancer cases strongly suggesting that this viral type has a biological advantage for transmission, persistency and transformation. The same phenomenon is observed albeit at a lower level for HPV-18 and HPV-45. Sexual behavioral patterns across age groups and populations are central to the description of the HPV circulation and of the risk of infection. The concept of group sexual behavior (in addition to individual sexual behavior) is important in exploring HPV transmission and has implications for defining and monitoring HPV and cancer prevention strategies. In natural history studies, the pattern of HPV DNA prevalence by age groups is similar to the patterns of HPV incidence. Rates of exposure in young women are high and often include multiple types. There is a spontaneous and rapid decrease of the HPV DNA detection rates in the middle-age groups followed by a second rise in the post-menopausal years. This article reviews: 1) the evidence in relation to the burden of HPV infections in the world and the contributions of each HPV type to the spectrum of cervical cellular changes spanning from normal cytology to invasive cervical cancer; 2) the critical role of the patterns of sexual behavior in the populations; and 3) selected aspects of the technical and methodological complexity of natural history studies of HPV and cervical neoplasia.