Beibei Lu

Efficacy and Safety of Prophylactic Vaccines against Cervical HPV Infection and Diseases among Women: A Systematic Review & Meta-Analysis

BackgroundWe conducted a systematic review and meta-analysis to assess efficacy and safety of prophylactic HPV vaccines against cervical cancer precursor events in women.MethodsRandomized-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 I2 statistic.ResultsSeven 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.ConclusionsProphylactic 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.

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

BACKGROUND 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. METHODS 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. RESULTS 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. CONCLUSION HPV infection in men was common, with relatively rapid rates of acquisition and clearance.

Age-specific prevalence of and risk factors for anal human papillomavirus (HPV) among men who have sex with women and men who have sex with men: the HPV in men (HIM) study.

BACKGROUND An increasing incidence of anal cancer among men suggests a need to better understand anal canal human papillomavirus (HPV) infection among human immunodeficiency virus-negative men. METHODS Genotyping for HPV was conducted on cells from the anal canal among men who have sex with women (MSW) and men who have sex with men (MSM), aged 18-70 years, from Brazil, Mexico, and the United States. Factors associated with anal HPV infection were assessed using multivariable logistic regression. RESULTS The prevalence of any HPV type and oncogenic HPV types did not differ by city. Anal canal HPV prevalence was 12.2% among 1305 MSW and 47.2% among 176 MSM. Among MSW, reporting a lifetime number of ≥ 10 female sex partners, a primary sexual relationship <1 year in duration, and a prior hepatitis B diagnosis were independently associated with detection of any anal HPV in multivariable analysis. Among MSM, a younger age, reporting ≥ 2 male anal sex partners in the past 3 months, and never using a condom for anal sex in the past 6 months were independently associated with detection of any anal HPV in multivariable analysis. CONCLUSIONS Number of sex partners was associated with anal HPV infection in both MSW and MSM. Anal HPV infection in men may be mediated by age, duration of sexual relationship, and condom use.

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

BACKGROUND 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. METHODS 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. RESULTS 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]). CONCLUSION 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.

Human Papillomavirus (HPV) 6, 11, 16, and 18 Seroprevalence Is Associated with Sexual Practice and Age: Results from the Multinational HPV Infection in Men Study (HIM Study)

Background: Few human papillomavirus (HPV) serology studies have evaluated type-specific seroprevalence of vaccine HPV types in men. This study investigates seroprevalence of HPV 6, 11, 16, and 18, and associated risk factors in men residing in three countries (United States, Mexico, and Brazil). Methods: Data from 1,477 men aged 18 to 70 enrolled in the HPV Infection in Men Study (HIM Study) were analyzed. Serum antibody testing was performed with virus-like particle-based ELISA. Potential risk factors were assessed for individual HPV types by the use of logistic regression. Results: Overall, HPV-6, 11, 16, and 18 seroprevalence was 14.8%, 17.3%, 11.2%, and 5.8%, respectively. Thirty-four percent of men were seropositive to one or more HPV types. When examined by sexual practice, 31.2% of men who had sex with women, 65.6% of men who had sex with men (MSM), and 59.4% of men who had sex with both men and women (MSMW) were seropositive to one or more HPV types. Seroprevalence increased with age among young-to-middle-aged men with significant upward age trends observed for HPV 11, 16, and 18. Men with multiple lifetime male anal sex partners were 2 to 4 times more likely to be HPV 6 or 11 seropositive and 3 to 11 times more likely to be HPV 16 or 18 seropositive. Conclusion: Our data indicate that exposures to vaccine HPV types were common in men and highly prevalent among MSM and MSMW. Impact: Our study provides strong evidence that the practice of same-sex anal intercourse is an independent risk factor for seroprevalence of individual vaccine HPV types. Examination of antibody responses to HPV infections at various anatomic sites in future studies is needed to elaborate on the mechanism. Cancer Epidemiol Biomarkers Prev; 20(5); 990–1002. ©2011 AACR.

The prevalence of genital HPV and factors associated with oncogenic HPV among men having sex with men and men having sex with women and men: The HIM study

Background: Comparative studies of genital human papillomavirus (HPV) among men having sex with men (MSM), men having sex with women and men (MSWM), and men having sex with women (MSW) have not been conducted so far; however, such comparisons may be important for planning prevention strategies like vaccination. Methods: Men, aged 18 to 70 years, were enrolled in a study of genital HPV in São Paulo, Brazil; Cuernavaca, Mexico; and Tampa, FL. Men were classified as MSM (n = 170), MSWM (n = 214), and MSW (n = 3326) based on self-reported sexual behavior. Genotyping for HPV was conducted on cells from the penis and scrotum. Prevalence data were adjusted by country. Factors potentially associated with genital HPV were assessed using multivariable Poisson regression. Results: Genital HPV prevalence was typically higher among MSWM than among MSM or MSW for groups of HPV genotypes including nononcogenic types (51%, 36%, and 42%, respectively), and multiple types (37%, 24%, and 29%, respectively). Age and alcohol consumption in the past month were associated with oncogenic HPV among both MSM and MSWM; however, there were no statistically significant associations between sexual behaviors and genital HPV among MSM or MSWM. Conclusions: Prevalence of genital HPV may be higher among MSWM than among MSW or MSM. Number of female sex partners was associated with genital HPV among MSW, but number of male anal sex partners was not associated with genital HPV among MSM and MSWM.

Prevalent Serum Antibody Is Not a Marker of Immune Protection against Acquisition of Oncogenic HPV16 in Men

In women, naturally induced anti-human papilloma virus (HPV) serum antibodies are a likely marker of host immune protection against subsequent HPV acquisition and progression to precancerous lesions and cancers. However, it is unclear whether the same is the case in men. In this study, we assessed the risk of incident genital infection and 6-month persistent genital infection with HPV16 in relation to baseline serostatus in a cohort of 2,187 men over a 48-month period. Genital swabs were collected every 6 months and tested for HPV presence. Incidence proportions by serostatus were calculated at each study visit to examine whether potential immune protection attenuated over time. Overall, incidence proportions did not differ statistically between baseline seropositive and seronegative men at any study visit or over the follow-up period. The risk of incident and 6-month persistent infection was not associated with baseline serostatus or baseline serum antibody levels in the cohort. Our findings suggest that baseline HPV seropositivity in men is not associated with reduced risk of subsequent HPV16 acquisition. Thus, prevalent serum antibodies induced by prior infection may not be a suitable marker for subsequent immune protection against genital HPV16 acquisition in men.

Seroprevalence of human papillomavirus (HPV) type 6 and 16 vary by anatomic site of HPV infection in men.

Background: It is largely unknown if antihuman papillomavirus (HPV) serum antibody responses vary by anatomic site of infection in men. Methods: This study assessed type-specific anti-HPV serum antibody prevalence associated with corresponding HPV DNA detection in the external genitalia and the anal canal of 1,587 heterosexual men and 199 men who have sex with men (MSM). Results: We observed that HPV 6 and 16 seroprevalence was higher in the presence of same HPV-type infection in the anal canal compared with same HPV-type infection in the external genitalia only, and among MSM compared with the heterosexual men. Seropositivity to HPV 6 was strongly associated with HPV 6 DNA detection in the anal canal but not in the external genitalia alone among both heterosexual men [adjusted prevalence ratio (APR), anal+/genital+ vs. anal−/genital−: 4.2, 95% confidence interval (CI), 11.7–10.5; anal+/genital− vs. anal−/genital−: 7.9 (95% CI, 3.7–17.0)] and MSM [APR, anal+/genital+ vs. anal−/genital−: 5.6 (95% CI, 2.7–11.9); anal+/genital− vs. anal−/genital−: 3.2 (95% CI, 2.1–4.9)]. Similar associations between seropositivity to HPV 16 and anal HPV 16 DNA detection were only observed in MSM [anal+/genital+ vs. anal−/genital−: 3.1 (95% CI, 2.0–5.0); anal+/genital− vs. anal−/genital−: 2.2 (95% CI, 1.3–3.5)]. Conclusion: Our data showed that seroprevalence varied by anatomic site of HPV infection, suggesting differences in epithelium type present at these anatomic sites may be relevant. Impact: Our finding is instrumental in advancing our understanding of immune mechanism involved in anatomic site–specific antibody response. Cancer Epidemiol Biomarkers Prev; 21(9); 1542–6. ©2012 AACR.

Cutaneous human papillomavirus types detected on the surface of male external genital lesions: a case series within the HPV Infection in Men Study.

BACKGROUND Cutaneous human papillomaviruses (HPVs) may be associated with cutaneous epithelial lesions and non-melanoma skin cancers. No study has systematically evaluated the presence of genus beta [β]-HPV in male genital skin or external genital lesions (EGLs) OBJECTIVES To examine cutaneous β-HPV types detected on the surface of EGLs in men and describe their presence prior to EGL development. STUDY DESIGN A retrospective case series was conducted among 69 men with pathologically confirmed EGLs (n=72) who participated in the HPV Infection in Men Study. Archived exfoliated cells collected from the surface of each EGL and normal genital skin specimens 6-12 months preceding EGL development were tested for β-HPV DNA using a type-specific multiplex genotyping assay. RESULTS β-HPV DNA was detected on 61.1% of all EGLs, with types 38 (16.7%), 5 (15.3%), and 12 (12.5%) most commonly identified. HPV prevalence differed across pathological diagnoses, with the largest number of β-HPV types detected on condylomas. Most β-HPV types were detected on normal genital skin prior to EGL development, though the prevalence was lower on EGLs compared to preceding normal genital skin. CONCLUSIONS EGLs and the normal genital skin of men harbor a large number of β-HPV types; however, it appears that β-HPVs are unrelated to EGL development in men. Despite evidence to support a causal role in skin carcinogenesis at UVR-exposed sites, cutaneous HPV appears unlikely to cause disease at the UVR-unexposed genitals.

Epidemiologic Factors Associated with Seropositivity to Human Papillomavirus Type 16 and 18 Virus–Like Particles and Risk of Subsequent Infection in Men

Our understanding of humoral response to human papillomavirus (HPV) infection has been mainly derived from studies in women. The role of serum antibodies in the natural history of HPV in men has yet to be investigated. Data from 285 male participants of a natural history study were used to determine the epidemiologic factors associated with HPV 16/18 seropositivity and explore the role of HPV 16 and 18 serum antibodies in subsequent HPV infections. Serum antibodies were detected by use of HPV 16– and 18 virus–like particles enzyme-linked immunoassay. Logistic regression and Generalized Estimating Equation was used for the evaluation of risk factors. The risk of subsequent HPV infection by baseline antibody status was assessed by incidence rate ratio and its confidence intervals. Men ages 36 to 44 years compared with men ages 18 to 25 years were four times more likely to be seropositive to HPV 16/18. In addition, being divorced, separated, or widowed; being a former smoker; and having sex with men was positively and independently associated with HPV 16/18 seropositivity. Our findings on the potential role of HPV 16 or 18 serum antibodies in subsequent infection were inconclusive. Large prospective studies are warranted to adequately address questions on the role of natural immunity in the natural history of HPV infections in men. Cancer Epidemiol Biomarkers Prev; 19(2); 511–6