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author:("Feng, xinghua")
1.  QUANTITATIVE HUMAN PAPILLOMAVIRUS 16 AND 18 LEVELS IN INCIDENT INFECTIONS AND CERVICAL LESION DEVELOPMENT 
Journal of medical virology  2009;81(4):713-721.
Human papillomavirus (HPV) RNA levels may be a more sensitive early indicator of predisposition to carcinogenesis than DNA levels. We evaluated whether levels of HPV-16 and HPV-18 DNA and messenger RNA (mRNA) in newly detected infections are associated with cervical lesion development. Female university students were recruited from 1990-2004. Cervical samples for HPV DNA, HPV mRNA, and Papanicolaou testing were collected tri-annually, and women were referred for colposcopically-directed biopsy when indicated. Quantitative real-time polymerase chain reaction of L1 and E7 DNA and E7 mRNA was performed on samples from women with HPV-16 and HPV-18 infections that were incidently detected by consensus PCR. Adjusting for other HPV types, increasing E7 cervical HPV-16 mRNA levels at the time of incident HPV-16 DNA detection were associated with an increased risk of cervical intraepithelial neoplasia grade 2 to 3 (HR per 1 log10 increase in mRNA=6.36,95%CI=2.00-20.23). Increasing HPV-16 mRNA levels were also associated with an increased risk of cervical squamous intraepithelial lesions; the risk was highest at the incident positive visit and decreased over time. Neither HPV-16 E7 DNA levels nor HPV-18 E7 DNA nor mRNA levels were significantly associated with cervical lesion development. Report of >1 new partner in the past 8 months (relative to no new partners) was associated with increased HPV mRNA (viral level ratio [VLR]=10.05,95%CI=1.09-92.56) and increased HPV DNA (VLR=16.80,95%CI=1.46-193.01). In newly detected HPV-16 infections, increasing levels of E7 mRNA appear to be associated with an increased risk of developing cervical pre-cancer.
doi:10.1002/jmv.21450
PMCID: PMC3984467  PMID: 19235870
HPV; viral load; mRNA; cervical pre-cancer
2.  Prevalence and risk factors for oncogenic HPV infections in high-risk mid-adult women 
Sexually transmitted diseases  2012;39(11):848-856.
Background
The epidemiology of high-risk (hr) HPV infections in mid-adult women with new sex partners is undefined.
Methods
We analyzed baseline data from 518 25–65 year old female online daters. Women were mailed questionnaires and kits for self-collecting vaginal specimens for PCR-based hrHPV testing. Risk factors for infection were identified using Poisson regression models to obtain prevalence ratios (PRs).
Results
The prevalence of hrHPV infection was 35.9%. In multivariate analysis restricted to sexually active women, the likelihood of hrHPV infection was associated with abnormal Pap test history (PR=1.42, 95% CI:1.10–1.84), lifetime number of sex partners >14 (relative to 1–4; PR=2.13, 95% CI:1.13–4.02 for 15–24 partners and PR=1.91, 95% CI:1.00–3.64 for ≥25 partners), male partners with ≥1 concurrent partnership (PR=1.34, 95% CI:1.05–1.71) and male partners whom the subject met online (PR=1.39, 95% CI:1.08–1.79). Age was inversely associated with infection only in women who were sexually inactive (PR=0.67 per 5-year age difference, adjusted for Pap history and lifetime number of partners). Compared to sexually inactive women, the likelihood of infection increased with increasing risk level, (from low-risk to high-risk partners) (p<.0001 by trend test). In multivariate analysis, infection with multiple versus single hrHPV types was inversely associated with ever having been pregnant (PR=0.64, 95% CI:0.46–0.90) and recent consistent condom use (PR=0.56, 95% CI:0.32–0.97), and positively associated with genital wart history (PR=1.43, 95% CI:1.03–1.99).
Conclusions
Measures of both cumulative and recent sexual history were associated with prevalent hrHPV infection in this high-risk cohort of mid-adult women.
doi:10.1097/OLQ.0b013e3182641f1c
PMCID: PMC3476060  PMID: 23064533
HPV; human papilloma virus; mid-adult; prevalence; risk factors
3.  Circumcision and acquisition of HPV infection in young men 
Sexually transmitted diseases  2011;38(11):1074-1081.
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.
doi:10.1097/OLQ.0b013e31822e60cb
PMCID: PMC3210112  PMID: 21992987
HPV; human papilloma virus; circumcision; epidemiology; risk factors
4.  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
5.  EARLY NATURAL HISTORY OF INCIDENT TYPE-SPECIFIC HUMAN PAPILLOMAVIRUS INFECTIONS IN NEWLY SEXUALLY ACTIVE YOUNG WOMEN 
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).
doi:10.1158/1055-9965.EPI-10-1108
PMCID: PMC3078690  PMID: 21173170
human papillomavirus; incidence; duration; persistence; women; epidemiology
6.  DETECTION OF GENITAL HPV TYPES IN FINGERTIP SAMPLES FROM NEWLY SEXUALLY ACTIVE FEMALE UNIVERSITY STUDENTS 
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.
doi:10.1158/1055-9965.EPI-10-0226
PMCID: PMC2901391  PMID: 20570905
human papillomavirus; fingertip; genital; women; epidemiology
7.  Evaluation of Transported Dry and Wet Cervical Exfoliated Samples for Detection of Human Papillomavirus Infection▿  
Journal of Clinical Microbiology  2010;48(9):3068-3072.
We determined the feasibility of human papillomavirus (HPV) detection in cervical exfoliated cells collected as dry swab samples. Both dry cervical swab and specimen transport medium (STM) cervical swab samples were collected from 135 patients attending either colposcopy or women's clinics in Guayaquil, Ecuador, who had a cytology diagnosis within 6 months. HPV was detected by dot blot hybridization and genotyped by the liquid bead microarray assay (LBMA). Overall, 23.1% of dry samples were positive for any high-risk HPV types, and 24.6% of STM samples were positive for any high-risk HPV types. Of 125 paired samples, the type-specific high-risk HPV proportion positive agreement was 60.7% (kappa, 0.69; 95% confidence interval [CI], 0.53 to 0.82). Of six women with cytological evidence of invasive cervical cancer, high-risk HPV DNA was detected in three of their STM samples and in five of their dry samples. Dry samples were more likely to be insufficient for HPV testing than STM samples. Consistent with this observation, the amount of genomic DNA quantitated with the β-actin gene was almost 20 times lower in dry samples than in STM samples when detected by the real-time TaqMan assay; however, HPV DNA viral loads in dry samples were only 1.6 times lower than those in matched STM samples. We concluded that exfoliated cervical cells could be collected as dry swab samples for HPV detection.
doi:10.1128/JCM.00736-10
PMCID: PMC2937663  PMID: 20610686
8.  Risk of Female Human Papillomavirus Acquisition Associated with First Male Sex Partner 
The Journal of infectious diseases  2008;197(2):279-282.
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.
doi:10.1086/524875
PMCID: PMC2875685  PMID: 18179386
9.  Development and Evaluation of a Liquid Bead Microarray Assay for Genotyping Genital Human Papillomaviruses▿ †  
Journal of Clinical Microbiology  2009;47(3):547-553.
We developed a liquid bead microarray (LBMA) assay for genotyping genital human papillomaviruses (HPVs) based on the MY09-MY11-HMB01 PCR system and the reverse line blot (RLB) assay probe sequences. Using individual HPV plasmids, we were able to detect as few as 50 copies per reaction. In two separate retrospective studies, the LBMA assay was compared to the RLB assay and to the Hybrid Capture II (hc2) assay. Testing was performed without knowledge of other assay results. In the first study, 614 cervical swab samples (enriched for HPV infection) from 160 young women were tested for HPV DNA, and 360 (74.8%) type-specific HPV infections were detected by both assays, 71 (14.8%) by the LBMA assay only, and 50 (10.4%) by the RLB assay only. Type-specific agreement for the two assays was excellent (99.1%; kappa = 0.85; 95% confidence interval [95% CI], 0.82 to 0.88). Samples with discrepant LBMA and RLB test results tended to have low viral loads by a quantitative type-specific PCR assay. In the second study, cervical swab samples from 452 women (including 54 women with histologically confirmed cervical-intraepithelial neoplasia grade 2 or worse [≥CIN2]) were tested initially by the hc2 and subsequently by the LBMA assay. The estimated sensitivities for ≥CIN2 were similar for the LBMA and hc2 assays (98.4% [95% CI, 95.0 to 100%] and 95.6% [95% CI, 89.2 to 100%], respectively). The percentages of negative results among 398 women without ≥CIN2 were similar for the LBMA and hc2 assays (45% and 50%, respectively). The repeat test reproducibility for 100 samples was 99.1% (kappa = 0.92; 95% CI, 0.90 to 0.95). We conclude that the new LBMA assay will be useful for clinical and epidemiological research.
doi:10.1128/JCM.01707-08
PMCID: PMC2650937  PMID: 19144800

Results 1-9 (9)