Male Circumcision for the Prevention of HSV-2 and HPV Infections and Syphilis

Male Circumcision for the Prevention of HSV-2 and HPV Infections and Syphilis

The causal role of human papillomavirus (HPV) in all cancers of the uterine cervix has been firmly established biologically and epidemiologically. 1 They are passed from person to person during sexual activity — generally during penile-vaginal or penile-anal sex. Unfortunately, the E7 protein is a very poor inducer of a cytotoxic T-cell response, when being used as antigen in DNA vaccination. In the current study, we explore the use of a human papillomavirus (HPV) pseudovirion to deliver a herpes simplex virus thymidine kinase (HSV-tk) gene to ovarian tumor cells. 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). Thus, other cofactors are necessary for progression from cervical HPV infection to cancer. However, premarital intercourse occurs at about a 95% rate in the U.S., and extramarital intercourse occurs at about the 40% level.

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). This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. 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). 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. It offers absolutely no protection against syphilis, gonorrhea, HIV — the virus that causes AIDS — and many other STIs. Thus, the potential efficacy of male circumcision for the prevention of sexually transmitted infections can be determined only in randomized trials. After maturation, the cell lysate was chilled on ice for 10 min.

We conducted two parallel but independent trials of male circumcision for the prevention of HIV infection and other sexually transmitted infections in Rakai, Uganda, as described previously.7,24 In the first trial (Rakai-1, which was funded by the National Institutes of Health), we enrolled 4996 HIV-negative, uncircumcised boys and men between the ages of 15 and 49 years who accepted voluntary HIV counseling and testing and agreed to learn their HIV results. The second trial (Rakai-2, which was funded by the Bill and Me-linda Gates Foundation) had as its primary goal the assessment of the safety of male circumcision and its effects on sexually transmitted infections in HIV-infected men and their partners. Surface cells from her cervix are collected and analyzed in the lab for the presence of pre-cancerous or cancerous cells. The two trials, which were conducted concurrently, had identical protocols. The purity of HPV pseudovirions was evaluated by running the fractions on 4–15% gradient sodium dodecyl sulfate-polyacrylamide gel electrophoresis. All subjects who were found to be HIV-positive were referred to an HIV treatment program funded by the U.S. President’s Emergency Plan for AIDS Relief (PEPFAR).

Male Circumcision for the Prevention of HSV-2 and HPV Infections and Syphilis
Affordable Care Act, there should be a significant reduction in the development of cervical cancer in HPV-infected women developing cervical cancer. Both the Rakai-1 and Rakai-2 trials were approved by four institutional review boards: the Science and Ethics Committee of the Uganda Virus Research Institute (Entebbe, Uganda), the HIV subcommittee of the National Council for Science and Technology (Kampala, Uganda), the Committee for Human Research at Johns Hopkins University’s Bloomberg School of Public Health (Baltimore, MD), and the Western Institutional Review Board (Olympia, WA). Luciferin (15 µg/ml) was added and incubated for 10 min. We performed physical examinations and conducted interviews to ascertain sociodemographic characteristics and rates of sexual practices at baseline and at 6, 12, and 24 months. Additional details on the study design, specimen testing, and analyses are presented in the Supplementary Appendix, available with the full text of this article at NEJM.org. HPV genotyping was performed with the use of the HPV Linear Array (Roche Diagnostics), as described previously.26,27 HPV genotypes 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66, and 68 were considered the primary high-risk (carcinogenic) genotypes.28,29 (We included HPV genotype 66 [HPV-66] in our definition of carcinogenic HPV genotypes after its reclassification, in 2005.29) For the primary analyses of HPV prevalence, we excluded subjects who were HPV-negative and had no detectable beta-globin in the sample, since the presence of cellular material could not be demonstrated. Active Treponema pallidum infection was determined by means of a positive rapid plasma re-agin test (Becton Dickinson) or a toluidine red unheated serum test (TRUST) (New Horizons Diagnostics) and was confirmed by a positive T.

An integration time of 2 min was used for luminescence image acquisition. For end points for HSV-2 infection and syphilis, we performed time-to-event analyses, using the protocol-specified Kaplan–Meier method, with the end point defined as the time to the detection of HSV-2 or syphilis seropositivity, with censoring of data at the last visit. In the primary intention-to-treat analysis, we performed an adjustment for baseline characteristics using a Cox proportional-hazards model for the time to detection of HSV-2 or syphilis seropositivity. In secondary analyses, adjustments were also made for the trial (Rakai-1 or Rakai-2), changes in sexual practices (number of sexual partners, condom use, and alcohol use with sexual intercourse), and symptoms of sexually transmitted infections (genital ulcers, urethral discharge, and dysuria) during follow-up as time-varying covariates. In addition, we conducted an as-treated analysis in which crossover subjects (i.e., subjects in the intervention group who did not undergo surgery and those in the control group who underwent surgery elsewhere) were classified according to their actual circumcision status. The mice were injected with 0.2 ml of 15 mg/ml beetle luciferin (potassium salt; Promega). Additional details regarding subgroup analyses of the incidence of HSV-2 infection according to covariates and HPV analysis are available in the Supplementary Appendix.

The rates of sexual practices and symptoms of sexually transmitted infections were tabulated at each follow-up visit, and differences between the two study groups were assessed with the use of chi-square tests. All reported P values are two-sided and have not been adjusted for multiple testing. Subjects were enrolled in the Rakai-1 trial from September 2003 through September 2005 and in the Raiki-2 trial from February 2004 through December 2006. The infected cells were treated with 0 µg/ml, 0.1 µg/ml, 1 µg/ml, or 10 µg/ml of ganciclovir for 72 hours and luciferase expression was examined by IVIS 200 system (Xenogen Corp., Alameda, CA, USA). For the analysis to determine HSV-2 seroconversion, we evaluated 3393 HIV-negative, HSV-2–negative, uncircumcised subjects between the ages of 15 and 49 years; of these subjects, 1684 had been randomly assigned to undergo immediate circumcision (intervention group) and 1709 to undergo circumcision in 24 months (control group). The retention rates at 24 months were 81.9% (1370 of 1673 subjects) in the intervention group and 82.0% (1395 of 1701) subjects in the control group. For the HSV-2 study population, baseline sociodemographic characteristics and rates of sexual practices and symptoms of sexually transmitted infections were similar in the two study groups ().

Subjects who were enrolled in the Rakai-2 trial had higher sexual-risk profiles at enrollment than subjects in the Rakai-1 trial because the Rakai-2 trial permitted enrollment of subjects who declined to learn their HIV status, whereas the Rakai-1 trial required receipt of HIV results. An integration time of 2 min was used for luminescence image acquisition. At 24 months in the intention-to-treat population, HSV-2 infection was detected in 114 subjects in the intervention group and in 153 subjects in the control group (). The cumulative probability of HSV-2 infection during the 24-month period was lower in the intervention group (7.8%) than in the control group (10.3%) with an unadjusted hazard ratio of 0.75 (95% CI, 0.60 to 0.94; P = 0.02). After adjustment for enrollment characteristics and rates of sexual practices and symptoms of sexually transmitted infections, the hazard ratio was 0.72 (95% CI, 0.56 to 0.92; P = 0.008). After adjustment for time-varying covariates during follow-up, the hazard ratio was 0.77 (95% CI, 0.62 to 0.97; P = 0.03). As shown in Figure S1, HPV-16/Luc psV was able to infect MOSEC tumor cells in vitro.

In separate analyses of data from the Rakai-1 and Rakai-2 trials, male circumcision reduced the incidence of HSV-2 infection in both trials. In the Rakai-1 trial, the cumulative probability of HSV-2 infection at 24 months in the intention-to-treat population was lower in the intervention group (7.7%) than in the control group (9.9%), with an unadjusted hazard ratio of 0.77 (95% CI, 0.59 to 0.99). In the Rakai-2 trial, the cumulative probability of HSV-2 infection was 8.6% in the intervention group and 14.0% in the control group (unadjusted hazard ratio, 0.59; 95% CI, 0.27 to 1.27). There was no significant difference in efficacy between the Rakai-1 trial and the Rakai-2 trial (P = 0.52 for interaction).

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Male circumcision for the prevention of HSV-2 and HPV infections and syphilis

Male circumcision for the prevention of HSV-2 and HPV infections and syphilis

Reduced risk of urinary tract infections in infants. It is a body-altering ritual, just like piercings or tattoos or feet-crushing (they used to crush women’s feet in China, because they thought it “looked” nicer). In uncircumcised using topical antibiotics may cause overgrowth of candida (balanitis). Many cut men are angry with their parents fro taking away parts of their body. I suspected herpes, and at 3 months took an IGG test. The role of circumcision as an intervention strategy to reduce sexual transmission of HIV warrants consideration. A secondary analysis included adjustments for changes in the number of sexual partners, condom use, alcohol use at the time of intercourse, and symptoms of sexually transmitted diseases.
Male circumcision for the prevention of HSV-2 and HPV infections and syphilis

According to multiple studies, the foreskin on uncut guys can be a breeding ground for sexually transmitted infections, including herpes, HPV and HIV. Poisson regression was used to estimate incidence-rate ratios for prevalence and 95% confidence intervals. I asked her is she had taken any std test before, she told me she NEVER done any sort of std test but suspected  herpes because she have high fever, feeling tired, whitish/yellowish discharge and so on.. Fleiss et al. I hate myself for being so careless….PS: I am abstaining from sex with my husband btw! Retention at 24 months was 82% in both groups. At 24 months in the intention-to-treat population, HSV-2 infection was detected in 114 subjects in the intervention group and in 153 subjects in the control group.

I see loose skin, I try to get rid of it. After adjustment for enrollment characteristics and rates of sexual practices and symptoms of sexually transmitted infections, the hazard ratio was 0.72 (95% CI: 0.56-0.92; P=0.008). After adjustment for time-varying covariates during follow-up, the hazard ratio was 0.77 (95% CI: 0.62-0.97; P=0.03). In the as-treated analysis, the unadjusted hazard ratio for detection of infection was 0.73 (95% CI: 0.59 to 0.93; P=0.01); after adjustment for baseline characteristics, the hazard ratio was 0.72 (95% CI: 0.59 to 0.91; P=0.009). In separate analyses of data from the Rakai-1 and Rakai-2 trials, male circumcision reduced the incidence of HSV-2 infection in both trials.

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