Background

The role of circumcision in male HPV acquisition is not clear.

Methods

Male university students (18–20 years of age) were recruited from 2003–2009 and followed tri-annually. Shaft/scrotum, glans, and urine samples were tested for 37 alpha HPV genotypes. Cox proportional hazards methods were used to evaluate the association between circumcision and HPV acquisition. Logistic regression was used to assess whether number of genital sites infected at incident HPV detection or site of incident detection varied by circumcision status.

Results

In 477 men, rates of acquiring clinically-relevant HPV types (high-risk types plus types 6 and 11) did not differ significantly by circumcision status (hazard ratio [HR] for uncircumcised relative to circumcised subjects: 0.9[95%CI:0.7–1.2]). However, compared to circumcised men, uncircumcised men were 10.1 (95%CI:2.9–35.6) times more likely to have the same HPV type detected in all 3 genital specimens than in a single genital specimen and were 2.7 (95%CI:1.6–4.5) times more likely to have an HPV-positive urine or glans specimen at first detection.

Conclusions

While the likelihood of HPV acquisition did not differ by circumcision status, uncircumcised men were more likely than circumcised men to have infections detected at multiple genital sites, which may have implications for HPV transmission.

BACKGROUND

Characterizing short-term detection patterns of young women’s incident alpha-genus human papillomavirus (HPV) infections may further understanding of HPV transmission.

METHODS

Between 2000–2007, we followed 18–22 year old female university students with triannual HPV DNA and Papanicolau testing. Using Kaplan-Meier methods, we estimated: duration of detectable, type-specific incident infections; time to re-detection (among infections that became undetectable); and time to cervical lesion development after incident infection. We evaluated risk factors for short-term persistent versus transient infection with logistic regression.

RESULTS

303 incident type-specific infections were detected in 85 sexually active women. Median time to first negative test after incident infection was 9.4 (95%CI:7.8–11.2) months; 90.6% of infections became undetectable within two years. 19.4% of infections that became undetectable were re-detected within one year. Cervical lesions were common, and 60% were positive for multiple HPV types in concurrent cervical swabs. Incident HPV detection in the cervix only (versus the vulva/vagina only or both sites) was associated with short-term transience.

CONCLUSIONS

While most incident infections became undetectable within two years, re-detection was not uncommon. Cervical lesions were a common early manifestation of HPV infection.

IMPACT

It remains unclear whether potentially modifiable risk factors can be identified to reduce infection duration (and transmission likelihood).

Background

Little is known about detection of genital human papillomavirus (HPV) types in women’s fingertips. The study objectives were to determine the presence of genital HPV types in fingertip samples and agreement between fingertip and genital samples for detecting HPV.

Methods

At tri-annual visits, genital and fingertip samples were collected from female university students and tested for 37 HPV genotypes by PCR-based assay. Type-specific concordance between paired fingertip and genital samples was evaluated using a kappa statistic for percent positive agreement (“kappa +”). Paired samples with type-specific concordant fingertip and genital results were selected for variant characterization.

Results

A total of 357 fingertip samples were collected from 128 women. HPV prevalence in fingertip samples was 14.3%. Although percent positive agreement between fingertips and genitals for detecting type-specific HPV was low (17.8%; kappa+=0.17, 95%CI:0.10–0.25), 60.4% of type-specific HPV detected in the fingertips was detected in a concurrent genital sample. All but one of 28 paired concordant samples were positive for the same type-specific variant in the fingertip and genital sample. Re-detection of HPV types at the subsequent visit was more common in genital samples (73.3%) than in fingertip samples (14.5%) (p<.001).

Conclusions

Detection of genital HPV types in the fingertips was not uncommon. While impossible to distinguish between deposition of DNA from the genitals to the fingertips and true fingertip infection, the rarity of repeat detection in the fingertips suggests that deposition is more common.

Impact

Finger-genital transmission is plausible, but unlikely to be a significant source of genital HPV infection.

To quantify the risk of human papillomavirus (HPV) acquisition associated with a first male sex partner and to identify associated risk factors, we analyzed data from women who were enrolled before or within 3 months of first intercourse with a male partner and were censored at the report of a second partner. The 1-year cumulative incidence of first HPV infection was 28.5% (95% confidence interval, 20.6%–38.6%) and increased to almost 50% by 3 years. The risk was increased when the first male partner was sexually experienced. Our results indicate a high risk of HPV infection in young women who have had just 1 male sex partner.

Background

The activities of Rac1 and Cdc42 are essential for HRas-induced transformation of rodent fibroblasts. What is more, expression of constitutively activated mutants of Rac1 and/or Cdc42 is sufficient for their malignant transformation. The role for these two Rho GTPases in HRas-mediated transformation of human fibroblasts has not been studied. Here we evaluated the contribution of Rac1 and Cdc42 to maintaining HRas-induced transformation of human fibroblasts, and determined the ability of constitutively activated mutants of Rac1 or Cdc42 to induce malignant transformation of a human fibroblast cell strain.

Methods

Under the control of a tetracycline regulatable promoter, dominant negative mutants of Rac1 and Cdc42 were expressed in a human HRas-transformed, tumor derived fibroblast cell line. These cells were used to determine the roles of Rac1 and/or Cdc42 proteins in maintaining HRas-induced transformed phenotypes. Similarly, constitutively active mutants were expressed in a non-transformed human fibroblast cell strain to evaluate their potential to induce malignant transformation. Affymetrix GeneChip arrays were used for transcriptome analyses, and observed expression differences were subsequently validated using protein assays.

Results

Expression of dominant negative Rac1 and/or Cdc42 significantly altered transformed phenotypes of HRas malignantly transformed human fibroblasts. In contrast, expression of constitutively active mutants of Rac1 or Cdc42 was not sufficient to induce malignant transformation. Microarray analysis revealed that the expression of 29 genes was dependent on Rac1 and Cdc42, many of which are known to play a role in cancer. The dependence of two such genes, uPA and VEGF was further validated in both normoxic and hypoxic conditions.

Conclusion(s)

The results presented here indicate that expression of both Rac1 and Cdc42 is necessary for maintaining several transformed phenotypes in oncogenic HRas transformed human cells, including their ability to form tumors in athymic mice. Our data also indicate that expression of either activated Rac1 or Cdc42 alone is not sufficient for malignant transformation of human fibroblasts, although each is required for specific transformed phenotypes. Furthermore, our study elucidates that the expression of several highly significant cancer related genes require the activities of Rac1 and/or Cdc42 which may also play a critical role in cellular transformation.