Background
Human papillomavirus (HPV) causes two types of external genital lesions (EGLs) in men: genital warts (condyloma) and penile intraepithelial neoplasia (PeIN).
Objective
The purpose of this study was to describe genital HPV progression to a histopathologically confirmed HPV-related EGL.
Design, Setting and Participants
A prospective analysis nested within the HPV Infection in Men (HIM) Study was conducted among 3033 men. At each visit, visually distinct EGLs were biopsied, subjected to pathological evaluation, and categorized by pathological diagnoses. Genital swabs and biopsies were used to identify HPV types using the Linear Array genotyping method for swabs and INNO-LiPA for biopsies.
Outcome Measurements
EGL incidence was determined among 1788 HPV-positive men, and cumulative incidence rates at 6, 12, and 24 months were estimated. The proportion of HPV infections that progressed to EGL was also calculated, along with median time to EGL development.
Results and Limitations
Among 1788 HPV-positive men, 92 developed an incident EGL during follow-up (9 PeIN and 86 condyloma). During the first 12 months of follow-up, 16% of men with a genital HPV6 infection developed a HPV6-positive condyloma, and 22% of genital HPV11 infections progressed to an HPV11-positive condyloma. During the first 12-months of follow-up, 0.5% of men with a genital HPV16 infection developed an HPV16-positive PeIN. Although we expected PeIN to be a rare event, the sample size for PeIN (n=10) limited the types of analyses that could be performed.
Conclusions
Most EGLs develop following infection with HPV 6, 11, or 16, all of which could be prevented with the 4-valent HPV vaccine.
Patient Summary
In this study, we looked at genital HPV infections that can cause lesions in men. The HPV that we detected within the lesions could be prevented through a vaccine.
In an attempt to identify novel small molecule ligands of CDK2 with potential as allosteric inhibitors, we devised a robust and cost-effective fluorescence-based high-throughput screening assay. The assay is based on the specific interaction of CDK2 with the extrinsic fluorophore 8-anilino-1-naphthalene sulfonate (ANS), which binds to a large allosteric pocket adjacent to the ATP site. Hit compounds which displace ANS directly or indirectly from CDK2 are readily classified as ATP site binders or allosteric ligands through the use of staurosporine, which blocks the ATP site without displacing ANS. Pilot screening of 1,453 compounds led to the discovery of 12 compounds with displacement activities (EC50 values) ranging from 6 to 44 μM, all of which were classified as ATP site-directed ligands. Four new Type I inhibitor scaffolds were confirmed by X-ray crystallography. While this small compound library contained only ATP-site directed ligands, the application of this assay to large compound libraries has the potential to reveal previously unrecognized chemical scaffolds suitable for structure-based design of CDK2 inhibitors with new mechanisms of action.
Background. Human papillomavirus virus type 16 (HPV-16) and HPV-18 cause a large proportion of oropharyngeal cancers, which are increasing in incidence among males, and vaccine efficacy against oral HPV infections in men has not been previously evaluated.Methods. Sera and saliva collected in mouthwash and Merocel sponges at day 1 and month 7 were obtained from 150 men aged 27–45 years from Tampa, Florida, and Cuernavaca, Mexico, who received Gardasil at day 1 and months 2 and 6. Specimens were tested for anti–HPV-16 and anti–HPV-18 immunoglobulin G (IgG) levels by an L1 virus-like particle–based enzyme-linked immunosorbent assay.Results. All participants developed detectable serum anti–HPV-16 and anti–HPV-18 antibodies, and most had detectable antibodies in both oral specimen types at month 7 (HPV-16 was detected in 93.2% of mouthwash specimens and 95.7% of sponge specimens; HPV-18 was detected in 72.1% and 65.5%, respectively). Antibody concentrations in saliva were approximately 3 logs lower than in serum. HPV-16– and HPV-18–specific antibody levels, normalized to total IgG levels, in both oral specimen types at month 7 were significantly correlated with serum levels (for HPV-16, ρ was 0.90 for mouthwash specimens and 0.92 for sponge specimens; for HPV-18, ρ was 0.89 and 0.86, respectively).Conclusions. This is the first study demonstrating that vaccination of males with Gardasil induces HPV antibody levels at the oral cavity that correlate with circulating levels.
Low- and high-risk HPV genotypes contribute to the EGL burden. Men remain susceptible to HPV-related EGLs throughout the life span, making it necessary to ensure the longevity of immune protection against the most common causative HPV genotypes.
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