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1.  Male circumcision and the incidence and clearance of genital human papillomavirus (HPV) infection in men: the HPV Infection in men (HIM) cohort study 
Background
Reported associations of male circumcision (MC) with human papillomavirus (HPV) infection in men have been inconsistent.
Methods
4,033 healthy men were examined every six months for a median of 17.5 months. In each study visit, exfoliated cell specimens from the coronal sulcus/glans penis, penile shaft, and scrotum were collected and combined into one sample per person for HPV DNA detection. Samples were tested for 37 HPV types. Cox proportional hazards models were used to evaluate the association between MC and the incidence and clearance of HPV infections and specific genotypes.
Results
The overall incidence of new HPV infections did not differ by MC status (for any HPV, adjusted hazard ratio (aHR) 1.08, 95% confidence interval (CI) 0.91-1.27). However, incidence was significantly lower among circumcised versus uncircumcised men for HPV types 58 (p = 0.01), 68 (p < 0.001), 42 (p = 0.01), 61 (p < 0.001), 71 (p < 0.001), 81 (p = 0.04), and IS39 (p = 0.01), and higher for HPV types 39 (p = 0.01) and 51 (p = 0.02). Despite the lack of an overall association in the risk of HPV clearance by MC (for any HPV, aHR 0.95, 95% CI 0.88-1.02), median times to clearance were significantly shorter among circumcised than uncircumcised men for HPV types 33 (p = 0.02) and 64 (p = 0.04), and longer for HPV types 6 (p < 0.001), 16 (p < 0.001), and 51 (p = 0.02).
Conclusions
MC is not associated with the incidence and clearance of genital HPV detection, except for certain HPV types. The use of a single combined sample from the penis and scrotum for HPV DNA detection likely limited our ability to identify a true effect of MC at the distal penis.
doi:10.1186/1471-2334-14-75
PMCID: PMC3925013  PMID: 24517172
Male circumcision; Genital; HPV; Incidence; Clearance
2.  Circumcision and Human Papillomavirus Infection in Men: A Site-Specific Comparison 
The Journal of infectious diseases  2008;197(6):787-794.
Background
Lack of circumcision has been identified as a risk factor for male genital human papillomavirus (HPV) infection, although this association has not been consistently supported.
Methods
Specimens for HPV testing were collected from a cohort of 379 (primarily heterosexual) adult males. HPV prevalence in the glans penis and coronal sulcus, penile shaft, scrotum, semen, and urine was compared by circumcision status.
Results
Overall, HPV DNA prevalence ranged from 6% in semen to 52% in the penile shaft. The prevalence of any HPV infection in the glans/corona was significantly higher in uncircumcised men (46%) than in circumcised men (29%) (odds ratio [OR], 1.96 [95% confidence interval {CI}, 1.02-3.75], adjusted for demographic characteristics and sexual history). Uncircumcised men also had an increased risk of oncogenic HPV infection (adjusted OR, 2.51 [95% CI, 1.11-5.69]) and infection with multiple HPV types (adjusted OR, 3.56 [95% CI, 1.50-8.50]). Among uncircumcised men, HPV prevalence in the foreskin (44%) was comparable to that in the glans/corona, and type-specific positivity was observed between the 2 sites (κ = 0.52).
Conclusions
Uncircumcised men have an increased risk of HPV infection, including with oncogenic HPV, specifically localized to the glans/corona, possibly because of its proximity to the foreskin, which may be particularly vulnerable to infection.
doi:10.1086/528379
PMCID: PMC2596734  PMID: 18284369
3.  Male circumcision and prevalence of genital human papillomavirus infection in men: a multinational study 
Background
Accumulated evidence from epidemiological studies and more recently from randomized controlled trials suggests that male circumcision (MC) may substantially protect against genital HPV infection in men. The purpose of this study was to assess the association between MC and genital HPV infection in men in a large multinational study.
Methods
A total of 4072 healthy men ages 18–70 years were enrolled in a study conducted in Brazil, Mexico, and the United States. Enrollment samples combining exfoliated cells from the coronal sulcus, glans penis, shaft, and scrotum were analyzed for the presence and genotyping of HPV DNA by PCR and linear array methods. Prevalence ratios (PR) were used to estimate associations between MC and HPV detection adjusting for potential confounders.
Results
MC was not associated with overall prevalence of any HPV, oncogenic HPV types or unclassified HPV types. However, MC was negatively associated with non-oncogenic HPV infections (PR 0.85, 95% confident interval: 0.76-0.95), in particular for HPV types 11, 40, 61, 71, and 81. HPV 16, 51, 62, and 84 were the most frequently identified genotypes regardless of MC status.
Conclusions
This study shows no overall association between MC and genital HPV infections in men, except for certain non-oncogenic HPV types for which a weak association was found. However, the lack of association with MC might be due to the lack of anatomic site specific HPV data, for example the glans penis, the area expected to be most likely protected by MC.
doi:10.1186/1471-2334-13-18
PMCID: PMC3554597  PMID: 23327450
Male circumcision; Genital; HPV; Non-oncogenic; Prevalence
4.  Effects of Genital Ulcer Disease and Herpes Simplex Virus Type 2 on the Efficacy of Male Circumcision for HIV Prevention: Analyses from the Rakai Trials 
PLoS Medicine  2009;6(11):e1000187.
Ron Gray and colleagues analyze data from two circumcision trials in Uganda to assess how HSV-2 status and genital ulcer disease affect the procedure's ability to reduce HIV infection.
Background
Randomized trials show that male circumcision (MC) reduces the incidence of HIV and herpes simplex virus type 2 (HSV-2) infections, and symptomatic genital ulcer disease (GUD). We assessed the role of GUD and HSV-2 in the protection against HIV afforded by MC.
Methods and Findings
HIV-uninfected men were randomized to immediate (n = 2,756) or delayed MC (n = 2,775) in two randomized trials in Rakai, Uganda. GUD symptoms, HSV-2 status, and HIV acquisition were determined at enrollment and at 6, 12, and 24 mo of follow up. Ulcer etiology was assessed by PCR. We estimated the prevalence and prevalence risk ratios (PRRs) of GUD in circumcised versus uncircumcised men and assessed the effects of HSV-2 serostatus as a risk-modifying factor for GUD. We estimated the proportion of the effect of MC on HIV acquisition that was mediated by symptomatic GUD, and by HSV-2 infection. Circumcision significantly reduced symptomatic GUD in HSV-2-seronegative men (PRR = 0.51, 95% [confidence interval] CI 0.43–0.74), HSV-2-seropositive men (PRR = 0.66, 95% CI 0.51–0.69), and in HSV-2 seroconverters (PRR = 0.48, 95% CI 0.30–0.79). The proportion of acute ulcers due to HSV-2 detected by PCR was 48.0% in circumcised men and 39.3% in uncircumcised men (χ2 p = 0.62). Circumcision reduced the risk of HIV acquisition in HSV-2 seronegative men (incidence rate ratio [IRR] = 0.34, 95% CI 0.15–0.81), and potentially in HSV-2 seroconverters (IRR = 0.56, 95% CI 0.19–1.57; not significant), but not in men with prevalent HSV-2 at enrollment (IRR = 0.89, 95% CI 0.49–1.60). The proportion of reduced HIV acquisition in circumcised men mediated by reductions in symptomatic GUD was 11.2% (95% CI 5.0–38.0), and the proportion mediated by reduced HSV-2 incidence was 8.6% (95% CI −1.2 to 77.1).
Conclusions
Circumcision reduced GUD irrespective of HSV-2 status, but this reduction played only a modest role in the protective effect of circumcision on HIV acquisition.
NIH Trial registration
ClinicalTrials.gov NCT00425984
Gates Foundation Trial registration
ClinicalTrials.gov NCT00124878
Please see later in the article for the Editors' Summary
Editors' Summary
Background
Acquired immunodeficiency syndrome (AIDS) has killed more than 25 million people since 1981, and more than 30 million people (22 million in sub-Saharan Africa alone) are now infected with the human immunodeficiency virus (HIV), which causes AIDS. There is no cure for HIV/AIDS. Consequently, prevention of HIV transmission is extremely important. Because HIV is most often spread through unprotected sex with an infected partner, individuals can reduce their risk of becoming infected with HIV by abstaining from sex, by having one or a few partners, and by always using a male or female condom. In addition, three large trials in sub-Saharan Africa (including one in Rakai, Uganda) recently reported that male circumcision—the removal of the foreskin, a loose fold of skin that covers the head of the penis—can halve HIV transmission rates in men. Thus, as part of its HIV prevention strategy, the World Health Organization now recommends that male circumcision programs be scaled up in countries where there is a generalized HIV epidemic and where few men are circumcised.
Why Was This Study Done?
It is still not clear why male circumcision reduces HIV acquisition in men. Certainly, the foreskin contains many cells that HIV can infect and the foreskin's delicate lining is thought to be particularly vulnerable to HIV infection partly because intercourse can cause small tears in it through which HIV can enter the body. But male circumcision also reduces genital ulcer disease—sores on the penis and other genital organs caused by infection with several sexually transmitted organisms including the herpes simplex virus type 2 (HSV-2). Genital ulcer disease, particularly when caused by HSV-2, is thought to increase a person's risk of acquiring HIV, so could male circumcision reduce HIV transmission rates because of its beneficial effects on genital ulcer disease rather than through its removal of foreskin tissue with its rich source of HIV target cells? In this study, the researchers investigate this question by re-analyzing data collected in two Ugandan trials of male circumcision for HIV prevention.
What Did the Researchers Do and Find?
In the Ugandan trials, the researchers randomly assigned about 5,500 HIV-uninfected men to immediate circumcision or to circumcision 24 months later. At enrollment, they asked the men whether they had any symptoms of genital ulcer disease (for example, a painful penile sore or genital itching), examined the men's genital areas, and took blood samples to test for HSV-2 infection. The researchers repeated these examinations and tests at 6 months, 12 months, and 24 months and tested the study participants for HIV infection. The researchers' statistical analysis of these data shows that circumcision approximately halved symptomatic genital ulcer disease in the study participants irrespective of their HSV-2 infection status. Circumcision reduced the risk of HIV acquisition in men without HSV-2 infection by two-thirds but did not affect HIV acquisition among men infected with HSV-2 at enrollment. Among the men who became infected with HSV-2 during the study, circumcision reduced the risk of HIV acquisition but this reduction in risk was not statistically significant. That is, it could have happened by chance. Finally, the researchers calculated that 11.2% of the observed reduction in HIV acquisition associated with circumcision was mediated by reductions in symptomatic genital ulcer disease and 8.6% was mediated by reductions in HSV-2 infections.
What Do These Findings Mean?
The findings of this study are limited by the small number of people in some of the subgroups analyzed and by genital ulcer disease being self-reported. Furthermore, the validity of some of the findings may be compromised because the analysis described here was not specified in the original trial protocol. Nevertheless, these findings suggest that the reduction of genital ulceration following circumcision plays only a minor part in the ability of male circumcision to reduce HIV acquisition in men. They also suggest that circumcision reduces genital ulcer disease primarily by reducing the rate of nonherpetic ulceration, including sores caused by mild trauma during intercourse. Thus, the researchers conclude, most of the reduction in HIV acquisition provided by male circumcision may be attributable to the removal of vulnerable foreskin tissue containing HIV target cells.
Additional Information
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1000187.
Information is available from the US National Institute of Allergy and Infectious Diseases on HIV infection and AIDS
HIV InSite has comprehensive information on all aspects of HIV/AIDS
Information is available from Avert, an international AIDS charity on many aspects of HIV/AIDS, including information on HIV and AIDS in Uganda, and on circumcision and HIV (in English and Spanish)
More information about male circumcision is available from the Clearinghouse on Male Circumcision
Information on the Rakai HIV prevention trial is available
The MedlinePlus Encyclopedia has a page on male genital sores (in English and Spanish)
The US National Institute of Allergy and Infectious Diseases provides information about genital herpes
The US Centers for Disease Control and Prevention also provides information on genital herpes (in English and Spanish)
doi:10.1371/journal.pmed.1000187
PMCID: PMC2771764  PMID: 19936044
5.  Clinical presentation of genital warts among circumcised and uncircumcised heterosexual men attending an urban STD clinic. 
Genitourinary Medicine  1993;69(4):262-264.
INTRODUCTION--A recent study comparing heterosexual men with and without confirmed sexually transmitted diseases (STDs) in an urban STD clinic showed that uncircumcised men were less likely than circumcised men to have genital warts detectable by clinical examination (adjusted odds ratio 0.7, 95% confidence interval 0.4, 0.9). Based on these initial findings we hypothesised that the appearance and anatomic distribution of genital warts, and possibly treatment response, may be different for circumcised and uncircumcised men. METHODS--The anatomic location, appearance, number of warts, and response to treatment was investigated through review of medical records of 459 heterosexual men with genital warts detected in 1988. RESULTS--Age- and race-adjusted estimates indicated that among men with genital warts, warts were detected much more commonly on the distal penis--that is, the corona, frenulum, glans or urethral meatus-, among uncircumcised men (26%) than among circumcised men (3%) (OR 10.0, 95% CI 3.9, 25.7). Where the appearance was specified, warts were more often described as condylomatous in uncircumcised men and slightly more often as papular in circumcised men. No significant difference between circumcised and uncircumcised men was seen in the number of return visits to the clinic for persistent warts after treatment with liquid nitrogen: 2.2 visits for 19 uncircumcised men and 2.3 visits for 149 circumcised men. CONCLUSION--Circumcised men were more likely than uncircumcised men to have genital warts, but when present, warts were more often located on the distal portion of the penis among uncircumcised men. This paradox is not understood, but could reflect either nonspecific resistance to proximal penile warts conferred by the foreskin, or heightened susceptibility to various HPV types in uncircumcised men, some of which may confer subsequent immunity to genital warts.
PMCID: PMC1195083  PMID: 7721284
6.  The Strong Protective Effect of Circumcision against Cancer of the Penis 
Advances in Urology  2011;2011:812368.
Male circumcision protects against cancer of the penis, the invasive form of which is a devastating disease confined almost exclusively to uncircumcised men. Major etiological factors are phimosis, balanitis, and high-risk types of human papillomavirus (HPV), which are more prevalent in the glans penis and coronal sulcus covered by the foreskin, as well as on the penile shaft, of uncircumcised men. Circumcised men clear HPV infections more quickly. Phimosis (a constricted foreskin opening impeding the passage of urine) is confined to uncircumcised men, in whom balanitis (affecting 10%) is more common than in circumcised men. Each is strongly associated with risk of penile cancer. These findings have led to calls for promotion of male circumcision, especially in infancy, to help reduce the global burden of penile cancer. Even more relevant globally is protection from cervical cancer, which is 10-times more common, being much higher in women with uncircumcised male partners. Male circumcision also provides indirect protection against various other infections in women, along with direct protection for men from a number of genital tract infections, including HIV. Given that adverse consequences of medical male circumcision, especially when performed in infancy, are rare, this simple prophylactic procedure should be promoted.
doi:10.1155/2011/812368
PMCID: PMC3113366  PMID: 21687572
7.  Low frequency of male circumcision and unwillingness to be circumcised among MSM in Buenos Aires, Argentina: association with sexually transmitted infections 
Objective
The aims of this study were to investigate the frequency of male circumcision among men who have sex with men (MSM) in Buenos Aires, Argentina; the association between circumcision and sexually transmitted infections (STIs); and, among those uncircumcised, the willingness to be circumcised.
Methods
A cross-sectional study was conducted among 500 MSM recruited through the respondent-driven sampling (RDS) technique. Participants underwent a consent process, responded to a Web-based survey that included questions on demographic information, sexual behaviour, and circumcision and provided biological samples. HIV, hepatitis B virus (HBV), hepatitis C virus (HCV), Treponema pallidum, and human papiloma virus (HPV) diagnoses were performed using standard methodologies. For all analyses, data were weighted based on participants’ network size.
Results
Only 64 (13%) of the 500 MSM in our study reported being circumcised. Among uncircumcised men (n=418), 302 (70.4%) said that they would not be willing to get circumcised even if the procedure could reduce the risk of HIV infection. When considering all participants, circumcision status was not significantly associated with HIV, HBV, HCV, T. pallidum or HPV infections. However, when we restricted the sample to men who do not practice receptive anal intercourse (RAI) and compared circumcised to uncircumcised men, the former (N=33) had no cases of HIV infection, while 34 of 231 (14.8%) uncircumcised men were HIV positive (p=0.020). Regarding HPV, uncircumcised men had a significantly larger number of different HPV types compared with circumcised men (mean 1.83 vs. 1.09, p<0.001) and a higher frequency of high-risk-HPV genotypes (47.6% vs. 12.5%, p=0.012).
Conclusions
Consistent with international evidence, male circumcision appears to have a partial protective effect among MSM. The efficacy of circumcision in reducing risk of HIV infection among MSM appears to be correlated with sexual practices. Given the lack of motivation among MSM with regard to circumcision, proper awareness on the risks and benefits of circumcision needs to be created, if circumcision has to be introduced as a prevention strategy.
doi:10.7448/IAS.16.1.18500
PMCID: PMC3676535  PMID: 23746302
men who have sex with men; circumcision; respondent-driven sampling; HPV; HIV; Buenos Aires
8.  Male circumcision decreases high-risk human papillomavirus viral load in female partners: a randomized trial in Rakai, Uganda 
Male circumcision (MC) reduces high-risk human papillomavirus (HR-HPV) infection in female partners. We evaluated the intensity of HR-HPV viral DNA load in HIV-negative, HR-HPV-positive female partners of circumcised and uncircumcised men. HIV-negative men and their female partners were enrolled in randomized trials of MC in Rakai, Uganda. Vaginal swabs were tested for HR-HPV genotypes by Roche HPV Linear Array which provides a semi-quantitative measure of HPV DNA by the intensity of genotype-specific bands (graded:1-4). We assessed the effects of MC on female HR-HPV DNA load by comparing high intensity linear array bands (3-4) to low intensity bands (1-2) using an intention-to-treat analysis. Prevalence risk ratios (PPR) of high intensity bands in partners of intervention versus control arm men were estimated using log-binomial regression with robust variance. The trial included 335 women with male partners in the intervention arm and 340 in the control arm. At enrollment, the frequency of HR-HPV high intensity linear array bands was similar in both study arms. At 24 months follow-up, the prevalence of high intensity bands among women with detectable HRHPV was significantly lower in partners of intervention arm (42.7%) than control arm men (55.1%, PRR= 0.78, 95%CI 0.65-0.94, p=0.02), primarily among incident HR-HPV infections (PRR=0.66, 95% CI 0.50-0.87, p=0.003), but not persistent infections (PRR=1.02, 95% CI 0.83-1.24). Genotypes with high HR-HPV band intensity were more likely to persist (adjHR=1.27 95% CI 1.07-1.50), irrespective of male partner circumcision status. MC reduces HR-HPV DNA load in newly infected female partners.
doi:10.1002/ijc.28100
PMCID: PMC3732529  PMID: 23400966
Human papillomavirus (HPV); male circumcision; Uganda; cervical cancer; sexually transmitted infections; viral shedding; viral load; linear array band intensity; HIV
9.  Association of the ANRS-12126 Male Circumcision Project with HIV Levels among Men in a South African Township: Evaluation of Effectiveness using Cross-sectional Surveys 
PLoS Medicine  2013;10(9):e1001509.
Betran Auvert and colleagues report findings from the Bophelo Pele project, a community-based HIV prevention intervention offering free voluntary medical male circumcision (VMMC), that demonstrate an association between VMMC roll-out and a reduction in the incidence and prevalence of HIV in the community.
Please see later in the article for the Editors' Summary
Background
Randomized controlled trials have shown that voluntary medical male circumcision (VMMC) reduces HIV infection by 50% to 60% in sub-Saharan African populations; however, little is known about the population-level effect of adult male circumcision (MC) as an HIV prevention method. We assessed the effectiveness of VMMC roll-out on the levels of HIV in the South African township of Orange Farm where the first randomized controlled trial (RCT) to test the effect of VMMC on HIV acquisition was conducted in 2002–2005.
Methods and Findings
The Bophelo Pele project is a community-based campaign against HIV, which includes the roll-out of free VMMC. A baseline cross-sectional biomedical survey was conducted in 2007–2008 among a random sample of 1,998 men aged 15 to 49 (survey response rate 80.7%). In 2010–2011, we conducted a follow-up random survey among 3,338 men aged 15 to 49 (survey response rate 79.6%) to evaluate the project. Participants were interviewed, blood samples were collected and tested for HIV and recent HIV infection (using the BED HIV incidence assay), and MC status was assessed through a clinical examination. Data were analyzed using multivariate and propensity statistical methods.
Owing to the VMMCs performed in the context of the RCT and the Bophelo Pele project, the prevalence rate of adult MC increased from 0.12 (95% CI 0.10–0.14) to 0.53 (95% CI 0.51–0.55). Without these VMMCs, the HIV prevalence rate in 2010–2011 would have been 19% (95% CI 12%–26%) higher (0.147 instead of 0.123).
When comparing circumcised and uncircumcised men, no association of MC status with sexual behavior was detected. Among circumcised and uncircumcised men, the proportion consistently using condoms with non-spousal partners in the past 12 months was 44.0% (95% CI 41.7%–46.5%) versus 45.4% (95% CI 42.2%–48.6%) with weighted prevalence rate ratio (wPRR) = 0.94 (95% CI 0.85–1.03). The proportion having two or more non-spousal partners was 50.4% (95% CI 47.9%–52.9%) versus 44.2% (95% CI 41.3%–46.9%) with wPRR = 1.03 (95% CI 0.95–1.10).
We found a reduction of BED-estimated HIV incidence rate ranging from 57% (95% CI 29%–76%) to 61% (95% CI 14%–83%) among circumcised men in comparison with uncircumcised men.
Conclusions
Findings suggest that the roll-out of VMMC in Orange Farm is associated with a significant reduction of HIV levels in the community. The main limitation of the study is that it was not randomized and cannot prove a causal association. The roll-out of VMMC among adults in sub-Saharan Africa should be an international priority and needs to be accelerated to effectively combat the spread of HIV.
Please see later in the article for the Editors' Summary
Editors' Summary
Background
Every year about 2.2 million people (mostly in sub-Saharan Africa) become infected with HIV, the virus that causes AIDS. There is no cure for HIV/AIDS. Consequently, prevention of HIV transmission is extremely important. Because HIV is most often spread through unprotected sex with an infected partner, individuals can reduce their risk of HIV infection by abstaining from sex, by having only one or a few sexual partners, and by always using a male or female condom. The results of three randomized controlled trials conducted in sub-Saharan Africa also suggest that voluntary medical male circumcision (VMMC)—the removal of the foreskin, a loose fold of skin that covers the head of the penis—can reduce the heterosexual acquisition of HIV in men by 50%–60%. In 2007, the World Health Organization (WHO) and the Joint United Nations Programme on HIV/AIDS (UNAIDS) recommended that VMMC should be offered as part of comprehensive HIV risk reduction programs in settings with generalized HIV epidemics and low levels of male circumcision and prioritized 14 east and southern African countries for VMMC roll-out.
Why Was This Study Done?
To date, about 3 million VMMCs have been performed for HIV prevention but it is not known whether “real world” VMMC roll-out programs will replicate the promising results obtained in the earlier trials. Indeed, there are fears that “risk compensation” (an increase in risky sexual behaviors after VMMC) might lead to increased HIV transmission in regions where VMMC is rolled out. In this study, the researchers use sequential cross-sectional surveys (studies that collect data from a group of people at a single time point) to investigate HIV infection levels in men in Orange Farm, a township in South Africa where one of the randomized controlled trials of VMMC was undertaken. The surveys were conducted before and after implementation of the Bophelo Pele project, a community-based campaign against HIV that was initiated in 2008 and that includes free VMMC.
What Did the Researchers Do and Find?
The researchers asked a random sample of nearly 2,000 men aged 15–49 years about their sexual behavior (for example, how many non-spousal partners they had had over the past year), and their intention to become circumcised if uncircumcised in a baseline survey in 2007–2008. The study participants were also offered HIV counseling and testing (including a test that indicated whether the participant had recently become HIV positive) and were examined to see whether they were already circumcised. A similar follow-up survey was conducted in 2010–2011 in which more than 3,000 men were invited to take part. At baseline, 12% of the men surveyed had been circumcised (a prevalence of circumcision of 12%) whereas in the follow-up survey, the overall prevalence of circumcision and the prevalence of circumcision among 15–29 year-olds (an important target group for VMMC roll-out) were 53% and 58%, respectively. The overall HIV prevalence at follow-up was 12% and the researchers estimated that without the VMMCs performed during the Bophelo Pele project and the preceding randomized control trial the prevalence of HIV among men living in Orange Farm would have been 15% in 2011. Using various cut-off values and corrections for a laboratory-based test to measure recent HIV infections, the researchers reported a reduction in the rate of new HIV infections (incidence rate) ranging from 57% to 61% among circumcised men in comparison with uncircumcised men. Importantly, there was no evidence of an association between circumcision status and risky sexual behavior but circumcision was associated with a reduction in the number of men who had recently become HIV positive.
What Do These Findings Mean?
These findings suggest that VMMC roll out in Orange Farm is associated with a reduction in HIV infection levels in the community and that circumcision is not associated with changes in sexual behavior that might affect HIV infection rates. They also suggest that VMMC roll-out is associated with a rapid uptake of VMMC, especially among young men, in an African community where male circumcision is not a social norm. Because this study is not a randomized controlled trial, it cannot establish cause and effect. Thus, although the observed reduction in HIV prevalence among circumcised men compared to uncircumcised men suggests that circumcision provided protection against HIV acquisition within the study population, the results do not conclusively prove this. The findings of this study nevertheless support the continuation and acceleration of the roll-out of adult VMMC in Africa although further studies are needed to show whether VMMC roll-out is also associated with a reduction in HIV acquisition among women and among uncircumcised men.
Additional Information
Please access these websites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001509.
Information and resources on male circumcision for HIV prevention are available
Information is available from the US National Institute of Allergy and infectious diseases on HIV infection and AIDS
NAM/aidsmap provides basic information about HIV/AIDS, summaries of recent research findings on HIV care and treatment, and information on male circumcision for the prevention of HIV transmission
Information is available from WHO and UNAIDS on all aspects of HIV/AIDS; the Clearinghouse on Male Circumcision, a resource provided by WHO, UNAIDS and other international bodies, provides information and tools for VMMC policy development and program implementation; a report entitled Progress in scaling up voluntary medical male circumcision for HIV prevention in East and Southern Africa, January-December 2011 is available
Information is available from Avert, an international AIDS charity on many aspects of HIV/AIDS, including information on HIV and AIDS in South Africa, on HIV prevention, and on circumcision and HIV (in English and Spanish)
A 2010 PLOS Medicine Research Article by Pascale Lissouba et al. provides more information about the Bophelo Pele project
Personal stories about living with HIV/AIDS are available through Avert, through Nam/aidsmap, and through the charity website Healthtalkonline; a personal story about circumcision in Zimbabwe is available
doi:10.1371/journal.pmed.1001509
PMCID: PMC3760784  PMID: 24019763
10.  Male circumcision is associated with a lower prevalence of human papillomavirus-associated penile lesions among Kenyan men 
Human papillomavirus (HPV)-associated penile lesions in men may increase the risk of HPV transmission to their female partners. Risk factor data on HPV-associated penile lesions are needed from regions with a high burden of cervical cancer. Visual inspection of the penis was conducted using a colposcope at the 24-month visit among participants in a randomized controlled trial of male circumcision in Kenya, from May 2006 to October 2007. All photos were read independently by two observers for quality control. Penile exfoliated cells sampled from the glans/coronal sulcus and the shaft were tested for HPV DNA using GP5+/6+ PCR and for HPV16, 18 and 31 viral loads using a real time PCR assay. Of 275 men, 151 were circumcised and 124 uncircumcised. The median age was 22 years. Circumcised men had a lower prevalence of flat penile lesions (0.7%) versus uncircumcised (26.0%); adjusted odds ratio [OR]=0.02; 95% confidence interval [CI]: 0.003–0.1). Compared to men who were HPV-negative, men who were HPV DNA positive (OR=6.5; 95%CI: 2.4–17.5) or who had high HPV16/18/31 viral load (OR=5.2; 95%CI: 1.1–24.4) had higher odds of flat penile lesions. Among men with flat penile lesions, HPV56 (29.0%) and 16 (25.8%) were the most common types. Flat penile lesions are much more frequent in uncircumcised men, and associated with higher prevalence of HPV and higher viral loads. This study suggests that circumcision reduces the prevalence of HPV-associated flat lesions and may ultimately reduce male to female HPV transmission.
doi:10.1002/ijc.26196
PMCID: PMC3262059  PMID: 21618520
Human papillomavirus; Penile lesions; Men; Circumcision; Kenya
11.  Circumcision and Sexual Behavior: Factors Independently Associated with Human Papillomavirus (HPV) Detection among Men in The HIM Study 
There is growing interest in understanding 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 non-oncogenic 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 three months. Oncogenic HPV detection was independently associated with lifetime and recent number of sexual partners, and having sex in the past three months. Non-Oncogenic 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.
doi:10.1002/ijc.24097
PMCID: PMC3466048  PMID: 19089913
HPV prevalence; males; international
12.  Male Circumcision and Anatomic Sites of Penile High-Risk Human Papillomavirus in Rakai, Uganda 
Male circumcision (MC) reduces penile high-risk human papillomavirus (HR-HPV) on the coronal sulcus and urethra. HR-HPV varies by anatomic site, and it is unknown whether MC decreases HR-HPV on the penile shaft. We assessed the efficacy of MC to reduce HR-HPV on the penile shaft and compared it to known efficacy of MC to reduce HR-HPV on the coronal sulcus. HIV-negative men randomized to receive immediate circumcision (intervention) or circumcision delayed for 24 months (control) were evaluated for HR-HPV at 12 months post-enrollment using the Roche HPV Linear Array assay. Among swabs with detectable beta-globin or HPV, year 1 HR-HPV prevalence on the coronal sulcus was 21.5% in the intervention arm and 36.3% in the control arm men (adjusted prevalence risk ratios (PRR)=0.57, 95%CI 0.39–0.84, p=0.005). On the shaft, year 1 HR-HPV prevalence was 15.5% in the intervention and 23.8% in the control arm (adjusted PRR=0.66, 95%CI 0.39–1.12, p=0.12). Efficacy of MC to reduce HR-HPV on the shaft was similar to efficacy on the coronal sulcus (p=0.52). In a sensitivity analysis in which swabs without detectable beta-globin or HPV were included as HPV negative, prevalence of HR-HPV on the shaft was lower in the intervention arm (7.8%) than control arm (13.6%) (PRR 0.57, 95%CI 0.33–0.99, p<0.05). HR-HPV was more frequently detected on the coronal sulcus than penile shaft among uncircumcised men (36.3% vs 23.8%, respectively, p=0.02) and circumcised men (21.5% vs 15.5%, respectively, p=0.24). MC reduced HR-HPV prevalence on both the coronal sulcus and shaft.
doi:10.1002/ijc.25957
PMCID: PMC3193547  PMID: 21462185
Male circumcision; human papillomavirus (HPV); HIV; Uganda; foreskin; penis; coronal sulcus; penile shaft; cervical cancer; sexually transmitted infections
13.  Male circumcision decreases acquisition and increases clearance of high risk human papillomavirus in HIV-negative men: a randomized trial in Rakai, Uganda 
The Journal of infectious diseases  2010;201(10):1455-1462.
Uncircumcised HIV-negative men aged 15-49 years were randomized to immediate circumcision (n=441) or delayed circumcision (n=399). HPV was detected by Roche HPV Linear Array at enrollment, 6, 12 and 24 months. Incident HR-HPV was estimated in men who acquired a new HR-HPV genotype. HR-HPV clearance was determined in men with prior genotype-specific HR-HPV infections. Rate ratios (RR) and 95% confidence intervals (95%CI) of HR-HPV acquisition were estimated by Poisson multiple regression
Enrollment characteristics were comparable between groups. HR-HPV incidence was 19.7/100 py in the intervention (70/355.8 py) and 29.4/100 py (125/424.8 py) in the control arm (RR=0.67, 95%CI 0.51-0.89, p = 0.006.) The incidence of multiple HR-HPV infections was 6.7/100 py in the intervention and 14.8/100 py in control arm (RR = 0.45, 95%CI 0.28-0.73), but there was no significant effect on single infections (RR=0.89, 95%CI 0.60-1.30). HR-HPV incidence was lower in the intervention arm for all genotypes and demographic/behavioral subgroups. The clearance of pre-existing HR-HPV infections was 215.8/100py (205/95 py) in intervention and 159.1/100py (255/160.25 py) in control arm men (adjRR=1.39, 95%CI 1.17-1.64).
Male circumcision reduces the incidence of multiple HR-HPV infections and increases clearance of HR-HPV infections in HIV-uninfected men.
The trial was registered with ClinicalTrials.gov numbers NCT00425984
doi:10.1086/652184
PMCID: PMC2882881  PMID: 20370483
14.  Male circumcision and common sexually transmissible diseases in a developed nation setting. 
Genitourinary Medicine  1994;70(5):317-320.
OBJECTIVE--To determine whether the circumcision status of men affected their likelihood of acquiring sexually transmissible diseases (STDs). DESIGN--A cross-sectional study employing an anonymous questionnaire, clinical examination and type specific serology for herpes simplex virus type 2 (HSV-2). SETTING--A public STD clinic in Sydney, Australia. SUBJECTS--300 consecutive heterosexual male patients. MAIN OUTCOME MEASURES--Associations between circumcision status and past or present diagnoses of STDs including HSV-2 serology and clinical pattern of genital herpes. RESULTS--185 (62%) of the men were circumcised and they reported similar ages, education levels and lifetime partner numbers as men who were uncircumcised. There were no significant associations between the presence or absence of the male prepuce and the number diagnosed with genital herpes, genital warts and non-gonococcal urethritis. Men who were uncircumcised were no more likely to be seropositive for HSV-2 and reported symptomatic genital herpes outbreaks of the same frequency and severity as men who were circumcised. Gonorrhoea, syphilis and acute hepatitis B were reported too infrequently to reliably exclude any association with circumcision status. Human immunodeficiency virus infection (rare among heterosexual men in the clinic) was an exclusion criterion. CONCLUSIONS--From the findings of this study, circumcision of men has no significant effect on the incidence of common STDs in this developed nation setting. However, these findings may not necessarily extend to other setting where hygiene is poorer and the spectrum of common STDs is different.
PMCID: PMC1195274  PMID: 8001942
15.  Circumcision and STD in the United States: cross sectional and cohort analyses 
Sexually Transmitted Infections  2000;76(6):474-479.
Background: Male circumcision status has been shown to be associated with sexually transmitted disease (STD) acquisition in some, but not all, studies. Most studies have been cross sectional.
Objectives: We examined the association between circumcision status and the prevalence and incidence of gonorrhoea, chlamydia, and syphilis.
Methods: We analysed cross sectional and cohort study data from a multicentre controlled trial in the United States. Between July 1993 and September 1996, 2021 men visiting public inner city STD clinics in the United States were examined by a clinician at enrolment and 1456 were examined at follow up visits 6 and 12 months later. At each visit, men had laboratory tests for gonorrhoea, chlamydia, and syphilis and were examined for circumcision status. We used multiple logisitic regression to compare STD risk among circumcised and uncircumcised men adjusted for potentially confounding factors.
Results: Uncircumcised men were significantly more likely than circumcised men to have gonorrhoea in the multivariate analyses, adjusted for age, race, and site, in both the cross sectional (odds ratio (OR), 1.3; 95% confidence interval (CI), 0.9 to 1.7) and in the cohort analysis (OR, 1.6; 95% CI, 1.0 to 2.6). There was no association between lack of circumcision and chlamydia in either the cross sectional (OR, 1.0; 95% CI 0.7-1.4) or the cohort analysis (OR, 0.9; 95% CI 0.5-1.5). The magnitude of association between lack of circumcision and syphilis was similar in the cross sectional (OR, 1.4; 95% CI 0.6 to 3.3) and cohort analysis (OR, 1.5; 95% CI 0.4 to 6.1).
Conclusion: Uncircumcised men in the United States may be at increased risk for gonorrhoea and syphilis, but chlamydia risk appears similar in circumcised and uncircumcised men. Our results suggest that risk estimates from cross sectional studies would be similar to cohort findings.
Key Words: circumcision; sexually transmitted diseases; United States
doi:10.1136/sti.76.6.474
PMCID: PMC1744239  PMID: 11221132
16.  Microbial Diversity of Genital Ulcer Disease in Men Enrolled in a Randomized Trial of Male Circumcision in Kisumu, Kenya 
PLoS ONE  2012;7(7):e38991.
Background
Medical male circumcision (MMC) reduces the risk of genital ulcer disease (GUD) in men by 50%. In Ugandan and Kenyan trials, a sexually transmissible agent was not identified in 50–60% of GUD specimens by polymerase chain reaction (PCR) assay. We sought to better define the etiology of GUD in men participating in the Kenyan trial and examine how MMC affects GUD etiology.
Methods
We defined GUD of unknown etiology as negative for HSV (type 1 and type 2), T. pallidum, and H. ducreyi by PCR, and negative for HSV-2 and T. pallidum by serology. We identified bacterial microbiota in a subset of 59 GUD specimens using multitag pyrosequencing of the 16S rRNA gene, and compared results by unknown vs. STI-associated etiology. Statistical analysis employed Bray-Curtis similarity measure of bacterial community by etiology, hierarchical clustering and logistic regression.
Results
In 59 GUD specimens from 59 men, 23 (39%) had unknown etiology. Bacterial diversity was greater in GUD of unknown than STI etiology (p = 0.01). Fusobacteria (Fusobacterium spp. and Sneathia spp.) were more commonly detected in men with GUD of unknown etiology [adjusted OR = 5.67; 95% CI: 1.63–19.8] as were Oxobacter spp. and Anaerovorax spp. [adjusted OR = 3.12; 95% CI: 0.83–11.7]. Sequences from these four anaerobic bacterial taxa were more often detected in uncircumcised men than circumcised men (p<0.05).
Conclusions
Anaerobic bacteria are more common in genital ulcers of uncircumcised men. The specific anaerobic bacteria associated with GUD of unknown etiology have cytotoxic properties that can exacerbate epithelial disruptions leading to ulcer-like appearance. MMC may reduce GUD through a reduction in these anaerobic bacteria.
doi:10.1371/journal.pone.0038991
PMCID: PMC3407166  PMID: 22848346
17.  Sexual risk behaviors, circumcision status and pre-existing immunity to adenovirus type 5 among men who have sex with men participating in a randomized HIV-1 vaccine efficacy trial: Step Study 
Background
The Step Study found that men who had sex with men (MSM) who received an adenovirus type 5 (Ad5) vector-based vaccine and were uncircumcised or had prior Ad5 immunity had a higher HIV incidence than MSM who received placebo. We investigated whether differences in HIV exposure, measured by reported sexual risk behaviors, may explain the increased risk.
Methods
Among 1,764 MSM in the trial, 724 were uncircumcised, 994 had prior Ad5 immunity and 560 were both uncircumcised and had prior Ad5 immunity. Analyses compared sexual risk behaviors and perceived treatment assignment among vaccine and placebo recipients, determined risk factors for HIV acquisition and examined the role of insertive anal intercourse in HIV risk among uncircumcised men.
Findings
Few sexual risk behaviors were significantly higher in vaccine vs. placebo recipients at baseline or during follow-up. Among uncircumcised men, vaccine recipients at baseline were more likely to report unprotected insertive anal intercourse with HIV negative partners (25.0% vs. 18.1%; p=0.03). Among uncircumcised men who had prior Ad5 immunity, vaccine recipients were more likely to report unprotected insertive anal intercourse with partners of unknown HIV status (46.0% vs. 37.5%; p=0.05). Vaccine recipients remained at higher risk of HIV infection compared to placebo recipients (HR =2.8; 95% CI:1.7, 6.8) controlling for potential confounders.
Interpretation
These analyses do not support a behavioral explanation for the increased HIV infection rates observed among uncircumcised men in the Step Study. Identifying biologic mechanisms to explain the increased risk is a priority.
This study is registered with ClinicalTrials.gov, number NCT00095576.
doi:10.1097/QAI.0b013e31825325aa
PMCID: PMC3392543  PMID: 22421748
HIV vaccines; gay men; sexual behaviors
18.  Aetiology of genital ulcer disease in female partners of male participants in a circumcision trial in Uganda 
Summary
HIV acquisition is associated with herpes simplex virus type 2 (HSV-2) infection and genital ulcer disease (GUD). Three randomized control trials demonstrated that male circumcision significantly decreases HIV, HSV-2, human papillomavirus and self-reported GUD among men. GUD is also decreased among female partners of circumcised men, but it is unknown whether male circumcision status affects GUD pathogens in female partners. For the evaluation of GUD aetiology, two separate multiplex assays were performed to detect Haemophilus ducreyi, Treponema pallidum, HSV-1 and HSV-2. Of all the female GUD swabs evaluated, 67.5% had an aetiology identified, and HSV-2 was the primary pathogen detected (96.3%). However, there was no difference in the proportion of ulcers due to HSV-2 or other pathogens between female partners of circumcised men (11/15, 73.3%) compared with uncircumcised men (15/25, 60.0%, P = 0.39). The seroprevalence of HSV-2 is high in this population and therefore most of the detected HSV-2 infections represent reactivation. Since GUD is associated with HIV acquisition and one-third of GUD in this study did not have an aetiological agent identified, further research is needed to better understand the aetiology of GUD in Africa, and its relationship to circumcision and HIV infection.
doi:10.1258/ijsa.2009.009067
PMCID: PMC2785854  PMID: 19710342
herpes simplex virus type 2 (HSV-2); T. pallidum (TP); H. ducreyi (HD); genital ulcer disease (GUD); HIV; circumcision
19.  Male Circumcision for the Prevention of HSV-2 and HPV Infections and Syphilis 
The New England journal of medicine  2009;360(13):1298-1309.
BACKGROUND
Male circumcision significantly reduced the incidence of human immunodeficiency virus (HIV) infection among men in three clinical trials. We assessed the efficacy of male circumcision for the prevention of herpes simplex virus type 2 (HSV-2) and human papillomavirus (HPV) infections and syphilis in HIV-negative adolescent boys and men.
METHODS
We enrolled 5534 HIV-negative, uncircumcised male subjects between the ages of 15 and 49 years in two trials of male circumcision for the prevention of HIV and other sexually transmitted infections. Of these subjects, 3393 (61.3%) were HSV-2–seronegative at enrollment. Of the seronegative subjects, 1684 had been randomly assigned to undergo immediate circumcision (intervention group) and 1709 to undergo circumcision after 24 months (control group). At baseline and at 6, 12, and 24 months, we tested subjects for HSV-2 and HIV infection and syphilis, along with performing physical examinations and conducting interviews. In addition, we evaluated a subgroup of subjects for HPV infection at baseline and at 24 months.
RESULTS
At 24 months, the cumulative probability of HSV-2 seroconversion was 7.8% in the intervention group and 10.3% in the control group (adjusted hazard ratio in the intervention group, 0.72; 95% confidence interval [CI], 0.56 to 0.92; P = 0.008). The prevalence of high-risk HPV genotypes was 18.0% in the intervention group and 27.9% in the control group (adjusted risk ratio, 0.65; 95% CI, 0.46 to 0.90; P = 0.009). However, no significant difference between the two study groups was observed in the incidence of syphilis (adjusted hazard ratio, 1.10; 95% CI, 0.75 to 1.65; P = 0.44).
CONCLUSIONS
In addition to decreasing the incidence of HIV infection, male circumcision significantly reduced the incidence of HSV-2 infection and the prevalence of HPV infection, findings that underscore the potential public health benefits of the procedure.
doi:10.1056/NEJMoa0802556
PMCID: PMC2676895  PMID: 19321868
20.  Increased risk of HIV acquisition among Kenyan men with human papillomavirus infection 
The Journal of infectious diseases  2010;201(11):1677-1685.
Background
Few data are available concerning the effect of human papillomavirus (HPV) infection on HIV acquisition.
Methods
HIV-seronegative, sexually active 18-24 year-old Kenyan men within a randomized trial of male circumcision provided penile exfoliated cells from two anatomical sites (glans/coronal sulcus, and shaft) at baseline. The GP5+/6+ PCR assay ascertained a wide range of HPV DNA types at the baseline visit. Risk of HIV infection [95% confidence interval (CI)] was estimated using Kaplan-Meier methods, and hazard ratios (HR)[95% CI] from proportional hazards models.
Results
Among 2,168 uncircumcised men with baseline HPV data, 1,089 (50%) were HPV DNA positive. Cumulative incidence of HIV infection by 42-months was 5.8% [95% CI 3.6, 7.9] in men with HPV-positive glans specimens versus 3.7% [1.8, 5.6] in men with HPV-negative glans specimens (p=0.01). Controlling for subsequent circumcision status, baseline HSV-2 serostatus, and sexual and sociodemographic risk factors, the HR of HIV infection in men with HPV-positive glans specimens was 1.8 [1.1, 2.9] compared to men with HPV-negative glans specimens.
Conclusion
Results suggest an independent, increased risk of HIV seroconversion among HPV positive men. If confirmed in other studies, HPV prevention could be another tool for HIV prevention.
doi:10.1086/652408
PMCID: PMC2873838  PMID: 20415595
Human immunodeficiency virus (HIV); human papillomavirus (HPV); circumcision; Kenya; men; acquisition; risk factors
21.  The Effect of Medical Male Circumcision on Urogenital Mycoplasma genitalium among Men in Kisumu, Kenya 
Sexually Transmitted Diseases  2012;39(4):276-280.
Background
We determined the prevalence of urethral Mycoplasma genitalium (MG) infection and whether infection was associated with circumcision status, among men enrolled in the randomized trial of medical male circumcision to prevent HIV acquisition in Kisumu, Kenya.
Methods
M. genitalium and Trichomonas vaginalis (TV) were detected in first void urine (FVU) by APTIMA transcription mediated amplification assay. FVU and urethral swabs were assessed for N. gonorrhoeae (NG) and C. trachomatis (CT) by polymerase chain reaction assay. HSV-2 antibodies were detected by IgG ELISA. Multivariable logistic regression identified factors associated with MG infection.
Results
Specimens were collected between July and September 2010, and 52 [9.9%; 95% CI: 7.3–12.4%] MG infections were detected among 526 men. NG and TV were not associated with MG. CT co-infection was 5.8% in MG-infected men, and 0.8% among MG-uninfected men (p=0.02). MG infection was predominantly asymptomatic (98%). The prevalence of MG was 13.4% in uncircumcised men vs. 8.2% in circumcised men (p=0.06). Being circumcised nearly halved the odds of MG [adjusted OR=0.54; 95% CI: 0.29–0.99], adjusted for other variables significant at the p<0.05 level: HSV-2 infection [aOR=2.05; 95% CI: 1.05–4.00], CT infection [aOR=2.69; 95% CI: 1.44–5.02], and washing the penis <=1 hour after sex [aOR=0.47; 95% CI: 0.24–0.95].
Conclusions
MG infection was reduced among men who were circumcised, adding to the benefits of male circumcision in preventing several sexually transmitted infections.
doi:10.1097/OLQ.0b013e318240189c
PMCID: PMC3306596  PMID: 22421693
circumcision; Mycoplasma genitalium; Kenya; HSV-2; Chlamydia trachomatis
22.  Willingness to Be Circumcised for Preventing HIV among Chinese Men Who Have Sex with Men 
AIDS patient care and STDs  2009;23(5):315-321.
Male circumcision can reduce the risk of HIV acquisition among heterosexual men, but its effectiveness is uncertain in men who have sex with men (MSM). Additionally, its acceptability among Chinese men is unknown given a lack of history and cultural norms endorsing neonatal and adult circumcision. This study evaluated the willingness to participate in a clinical trial of circumcision among 328 Chinese MSM. Some 11.6% respondents reported having been circumcised, most of them due to a tight foreskin. Of 284 uncircumcised MSM, 16.9% said they were absolutely willing to participate, 26.4% were probably, 28.9% were probably not, and 27.8% were absolutely not; 81% said male circumcision would help maintain genital hygiene. The major motivators for willingness to participate included contribution to AIDS scientific research and getting free medical service. Men also had concerns about ineffectiveness of circumcision in reducing HIV/sexually transmitted infection (STI) risks and side effects of the surgery. Those who did not have a Beijing resident card (adjusted odds ratio [AOR], 1.99; 95% confidence interval [CI], 1.17–3.38), did not find sexual partners through the Internet (AOR, 2.13; 95% CI, 1.21–3.75), and were not concerned about the effectiveness of circumcision (AOR, 2.37; 95% CI, 1.34–4.19) were more likely to be willing to participate in a trial. The study suggests that circumcision is uncommon among Chinese MSM. Considerable community education will be needed in circumcision advocacy among MSM in China. A clinical trial for efficacy among MSM should be considered.
doi:10.1089/apc.2008.0199
PMCID: PMC2743100  PMID: 19335172
23.  Willingness to Be Circumcised for Preventing HIV among Chinese Men Who Have Sex with Men 
AIDS Patient Care and STDs  2009;23(5):315-321.
Abstract
Male circumcision can reduce the risk of HIV acquisition among heterosexual men, but its effectiveness is uncertain in men who have sex with men (MSM). Additionally, its acceptability among Chinese men is unknown given a lack of history and cultural norms endorsing neonatal and adult circumcision. This study evaluated the willingness to participate in a clinical trial of circumcision among 328 Chinese MSM. Some 11.6% respondents reported having been circumcised, most of them due to a tight foreskin. Of 284 uncircumcised MSM, 16.9% said they were absolutely willing to participate, 26.4% were probably, 28.9% were probably not, and 27.8% were absolutely not; 81% said male circumcision would help maintain genital hygiene. The major motivators for willingness to participate included contribution to AIDS scientific research and getting free medical service. Men also had concerns about ineffectiveness of circumcision in reducing HIV/sexually transmitted infection (STI) risks and side effects of the surgery. Those who did not have a Beijing resident card (adjusted odds ratio [AOR], 1.99; 95% confidence interval [CI], 1.17–3.38), did not find sexual partners through the Internet (AOR, 2.13; 95% CI, 1.21–3.75), and were not concerned about the effectiveness of circumcision (AOR, 2.37; 95% CI, 1.34–4.19) were more likely to be willing to participate in a trial. The study suggests that circumcision is uncommon among Chinese MSM. Considerable community education will be needed in circumcision advocacy among MSM in China. A clinical trial for efficacy among MSM should be considered.
doi:10.1089/apc.2008.0199
PMCID: PMC2743100  PMID: 19335172
24.  Risk Compensation Is Not Associated with Male Circumcision in Kisumu, Kenya: A Multi-Faceted Assessment of Men Enrolled in a Randomized Controlled Trial 
PLoS ONE  2008;3(6):e2443.
Background
Three randomized controlled trials (RCTs) have confirmed that male circumcision (MC) significantly reduces acquisition of HIV-1 infection among men. The objective of this study was to perform a comprehensive, prospective evaluation of risk compensation, comparing circumcised versus uncircumcised controls in a sample of RCT participants.
Methods and Findings
Between March 2004 and September 2005, we systematically recruited men enrolled in a RCT of MC in Kenya. Detailed sexual histories were taken using a modified Timeline Followback approach at baseline, 6, and 12 months. Participants provided permission to obtain circumcision status and laboratory results from the RCT. We evaluated circumcised and uncircumcised men's sexual behavior using an 18-item risk propensity score and acquisition of incident infections of gonorrhea, chlamydia, and trichomoniasis. Of 1780 eligible RCT participants, 1319 enrolled (response rate = 74%). At the baseline RCT visit, men who enrolled in the sub-study reported the same sexual behaviors as men who did not. We found a significant reduction in sexual risk behavior among both circumcised and uncircumcised men from baseline to 6 (p<0.01) and 12 (p = 0.05) months post-enrollment. Longitudinal analyses indicated no statistically significant differences between sexual risk propensity scores or in incident infections of gonorrhea, chlamydia, and trichomoniasis between circumcised and uncircumcised men. These results are based on the most comprehensive analysis of risk compensation yet done.
Conclusion
In the context of a RCT, circumcision did not result in increased HIV risk behavior. Continued monitoring and evaluation of risk compensation associated with circumcision is needed as evidence supporting its' efficacy is disseminated and MC is widely promoted for HIV prevention.
doi:10.1371/journal.pone.0002443
PMCID: PMC2409966  PMID: 18560581
25.  Serum Antibody Response Following Genital α9 Human Papillomavirus Infection in Young Men 
The Journal of Infectious Diseases  2011;204(2):209-216.
Background. Although the prevalence of human papillomavirus (HPV) genital infection is similarly high in males and females, seroprevalence is lower in males. This study assessed rates and determinants of seroconversion after detection of genital HPV infection in young men.
Methods. We investigated HPV type-specific seroconversion in a cohort of heterosexual male university students who had an α9 HPV type (HPV-16, -31, -33, -35, -52, -58, or -67) detected in the genital tract (n = 156). HPV DNA and antibodies were detected and typed using liquid bead-based multiplex assays. We calculated seroconversion using Kaplan–Meier survival analysis. Cox proportional hazards models with generalized estimating equations were used to examine associations with seroconversion.
Results. Within 24 months of detecting genital HPV infection, type-specific seroconversion ranged from 4% for HPV–52 to 36% for HPV-31. HPV-16 seroconversion at 24 months was 13% (95% confidence interval [CI], 7%–25%). Among incident HPV infections, ever cigarette smoking and infection site(s) (shaft/scrotum and glans/urine vs shaft/scrotum or glans/urine only) were positively associated with type-specific seroconversion.
Conclusions. For each of the α9 HPV types, type-specific seroconversion within 24 months was observed in 36% or less of infected men. Seroconversion might be related to cigarette smoking and genital site(s) infected.
doi:10.1093/infdis/jir242
PMCID: PMC3114468  PMID: 21673030

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