Shu Kuang Lee

Comparison of Human Papillomavirus Types 16, 18, and 6 Capsid Antibody Responses Following Incident Infection

The relationship between human papillomavirus (HPV) DNA in the genital mucosa and serum IgG to HPV-16, -18, and -6 was studied in a cohort of 588 college women. Among women with incident HPV infections, 59.5%, 54.1%, and 68.8% seroconverted for HPV-16, -18, or -6, respectively, within 18 months of detecting the corresponding HPV DNA. Transient HPV DNA was associated with a failure to seroconvert following incident HPV infection; however, some women with persistent HPV DNA never seroconverted. Antibody responses to each type were heterogeneous, but several type-specific differences were found: seroconversion for HPV-16 occurred most frequently between 6 and 12 months of DNA detection, but seroconversion for HPV-6 coincided with DNA detection. Additionally, antibody responses to HPV-16 and -18 were significantly more likely to persist during follow-up than were antibodies to HPV-6.

Development and Duration of Human Papillomavirus Lesions, after Initial Infection

BACKGROUND To determine the potential value of human papillomavirus (HPV) vaccines, information concerning the incidence and duration of clinically important lesions is needed. METHODS A total of 603 female university students were followed for a mean duration of 38.8 months. Triannual gynecologic examinations included cervical and vulvovaginal specimen collection for Pap and HPV DNA testing. Women with cytologic evidence of a high-grade squamous intraepithelial lesion (SIL) were referred for colposcopically directed biopsy. RESULTS Among women with incident HPV infection, the 36-month cumulative incidence of cervical SILs found by cytologic testing (47.2%; 95% confidence interval [CI], 38.9%-56.4%) was higher than that of vaginal SILs (28.8%; 95% CI, 21.3%-38.2%). The median time to clearance of cervical and vaginal SILs was 5.5 and 4.7 months, respectively. Among women with incident HPV-16 or HPV-18 infection, the 36-month cumulative incidence of cervical intraepithelial neoplasia (CIN) grade 2 was 20.0% (95% CI, 10.8%-35.1%), and that of CIN grade 3 was 6.7% (95% CI, 2.5%-17.0%). The 36-month cumulative incidence of clinically ascertained genital warts among women with incident HPV-6 or HPV-11 infection was 64.2% (95% CI, 50.7%-77.4%). CONCLUSIONS Intraepithelial lesions are common early events among women with incident HPV infection, and the interval between incident HPV-16 or HPV-18 infection and biopsy-confirmed CIN grade 2-3 appears to be relatively short.

Evaluation of Genital Sites and Sampling Techniques for Detection of Human Papillomavirus DNA in Men

To evaluate methods for detection of genital human papillomavirus (HPV) DNA in men, samples were obtained from 3 consecutive groups of 10 men attending a sexually transmitted disease clinic by use of (1) a saline-wetted Dacron swab alone, (2) a saline-wetted cytobrush, or (3) emery paper (600A-grit Wetordry Tri-M-ite; 3M) abrasion followed by a saline-wetted Dacron swab. By use of a polymerase chain reaction-based assay, 45% of emery-paper samples were found to be positive for beta-globin, compared with 23% of swab-alone and 0% of cytobrush samples. Subsequently, emery paper and saline-wetted Dacron swabs were used to obtain penile shaft, glans, foreskin, and scrotum samples from 318 male university students. Urine samples were also obtained. Of 1323 samples tested, 1288 (97%) were found to be positive for beta-globin. HPV DNA was detected in samples from 104 men (33%): 24% from the penile shaft, 16% from the glans, 28% from the foreskin, 17% from the scrotum, and 6% in urine. The HPV prevalence was similar for circumcised and uncircumcised men. Testing multiple sites increased the number of men for whom HPV DNA was detected.

Genital Human Papillomavirus Infection in Men: Incidence and Risk Factors in a Cohort of University Students

BACKGROUND In contrast to the wealth of data on human papillomavirus (HPV) infections in women, much less is known about HPV in men. METHODS Between June 2003 and March 2006, a total of 240 heterosexually active male university students 18-20 years of age were recruited for participation in a cohort study of HPV infection. Genital cell samples were collected, at 4-month intervals, for HPV-DNA analysis by polymerase chain reaction. The subjects maintained a Web-based journal of sexual activity. RESULTS At 24 months, the cumulative incidence of new infection of any genital HPV type was 62.4% (95% confidence interval [CI], 52.6%-72.2%). Acquisition rates did not differ by genital site (i.e., glans, penile shaft, or scrotum) of initial detection (P=.86). The most commonly detected types were HPV-84 and HPV-16. In multivariate analysis, a report of a new sex partner during the prior 0-4 (hazards ratio [HR], 2.0 [95% CI, 1.3-3.0]) and 5-8 (HR, 1.8 [95% CI, 1.2-2.7]) months and a history of smoking (HR, 1.6 [95% CI, 1.1-2.4]) were associated with an elevated risk of HPV acquisition. CONCLUSION Genital HPV infection is common and multifocal in young men, and its incidence is higher than that reported for similar cohorts of young women. The high rates of HPV infection in men should be considered when strategies for the prevention of HPV infection in female adolescents and young women are being developed.

Men's perceptions and knowledge of human papillomavirus (HPV) infection and cervical cancer.

The authors assessed young mens knowledge and perceptions of genital human papillomavirus (HPV) infection to identify factors that predict intention to make positive behavioral changes. Male university students aged 18 to 25 years completed a self-report instrument to assess knowledge and perceptions of genital HPV infection. If diagnosed with HPV, most men (95%) reported that they would use condoms with new partners. The intention to reduce number of sex partners was associated with an understanding that HPV may have severe consequences for women, whereas intention to encourage female sex partners to undergo Pap smear screening was associated with increased general knowledge of HPV infection. The authors concluded that it is important to include men in HPV education and prevention efforts, especially within the context that HPV may lead to cervical cancer in female partners.

Rates and determinants of oral human papillomavirus infection in young men.

Background Little is known about the rates and determinants of oral human papillomavirus (HPV) infection, an infection that is etiologically linked with oropharyngeal cancers. Methods A cohort of male university students (18–24 years) was examined every 4 months (212 men, 704 visits). Oral specimens were collected via gargle/rinse and swabbing of the oropharynx. Genotyping for HPV-16 and 36 other &agr;-genus types was performed by polymerase chain reaction–based assay. Data on potential determinants were gathered via clinical examination, in-person questionnaire, and biweekly online diary. Hazards ratios (HR) were used to measure associations with incident infection. Results Prevalence of oral HPV infection at enrollment was 7.5%, and 12-month cumulative incidence was 12.3% (95% confidence interval [CI], 7.0, 21.3). Prevalence of oral HPV-16 was 2.8% and 12-month cumulative incidence was 0.8% (95% CI, 0.1%–5.7%). None of the incident oral HPV infections and 28.6% of the prevalent oral HPV infections were detected more than once. In a multivariate model, incident oral HPV infection was associated with recent frequency of performing oral sex (≥1 per week: HR, 3.7; 95% CI, 1.4–9.8), recent anal sex with men (HR, 42.9; 95% CI, 8.8–205.5), current infection with the same HPV type in the genitals (HR, 6.2; 95% CI, 2.4–16.4), and hyponychium (HR, 11.8, 95% CI, 4.1–34.2). Conclusions Although nearly 20% of sexually active male university students had evidence of oral HPV infection within 12 months, most infections were transient. Human papillomavirus type 16 was not common. Sexual contact and autoinoculation appeared to play independent roles in the transmission of &agr;-genus HPV to the oral cavity of young men.

Detection of Cervical Antibodies to Human Papillomavirus Type 16 (HPV-16) Capsid Antigens in Relation to Detection of HPV-16 DNA and Cervical Lesions

A more sensitive luminescence immunoassay (LIA) for human papillomavirus type 16 (HPV-16) was developed and used to measure HPV-16 antibodies in cervical samples from 292 college-aged women who were examined at 4-month intervals. Of the 609 collected samples, IgG, IgA, and secretory piece-associated antibodies to HPV-16 were detected in 12%, 6%, and 8%, respectively, of samples tested. Cervical IgG antibodies were most strongly associated with HPV-16 DNA detected within the previous 12 months (odds ratio, 3.3; 95% confidence interval, 1.4-7.8). Secretory IgA (cervical IgA- and secretory piece-positive) was most strongly associated with detection of a squamous intraepithelial lesions 4-8 months earlier (odds ratio, 6.4; 95% confidence interval, 1.9-21.8). As with serum HPV-16 antibodies, there appears to be a several-month delay between cervical HPV infection and detection of cervical antibodies.

The effect of vaginal speculum lubrication on the rate of unsatisfactory cervical cytology diagnosis

OBJECTIVE Nonlubricated plastic specula can adhere to the vaginal introitus and cause discomfort with pelvic examination. We wanted to see if application of water‐soluble gel lubricant to the plastic vaginal speculum would change the unsatisfactory cervical cytology diagnosis rate. METHODS Five public health family planning clinic sites were randomized to either water‐soluble gel or water only as lubricant during speculum examination for cervical cytology collection. The pathologists were unaware of the assignment of lubricant use. The cumulative rates of cervical cytology diagnoses were calculated for 6 months before, 6 months during, and 6 months after the intervention. RESULTS From July 1998 through December 1999, 8534 Papanicolaou smears were collected, with 1440 using gel lubrication from January 1999 through June 1999. Rates of unsatisfactory smears for lubricant use clinics were 1.4% during use of lubricant and 1.4% without use (odds ratio [OR] 1.0; 95% confidence interval [CI] 0.6, 1.8). Rates of unsatisfactory smears for lubricant use versus nonlubricant use clinics during the gel intervention period were 1.4% versus 1.3% (OR 1.1; 95% CI 0.6, 2.0). There were no significant differences for the rates of atypical squamous cells of undetermined significance, low‐grade squamous intraepithelial lesion, high‐grade squamous intraepithelial lesion, or atypical glandular cells of undetermined significance within or between lubricant and nonlubricant clinics for each 6‐month period. There were no cases of invasive cancer. CONCLUSION The use of a small amount of water‐soluble gel lubricant on the outer inferior blade of the plastic vaginal speculum does not change cervical cytology results in a young, reproductive‐age population.

Characterization of IgA response among women with incident HPV 16 infection.

Previous studies have characterized the prevalence and duration of serum IgG antibodies to human papillomavirus type 16 (HPV 16) in a well-studied cohort of college women, using viruslike particle- (VLP) based ELISAs. In this study IgA antibodies in cervical secretions and sera were examined using a newly developed capsomer-based ELISA and the patterns observed for serum IgG, serum IgA, and cervical IgA antibodies were compared. The median time to antibody detection from the first detection of HPV 16 DNA was 10.5 months for IgA in cervical secretions and 19.1 months for serum IgA. Serum IgA antibody conversion was observed less frequently and occurred later than IgA conversion in cervical secretions (P = 0.011) or serum IgG conversion (P = 0.051). The median time to antibody reversion, following seroconversion, was 12.0 months for IgA in cervical secretions and 13.6 months for serum IgA, whereas approximately 20% of women with serum IgG antibodies reverted within 36 months. Thus, the duration of IgA in cervical secretions and sera was shorter than the duration of serum IgG (P = 0.007 and 0.001).

Development of Genital Warts after Incident Detection of Human Papillomavirus Infection in Young Men

Determining the rate at which men develop genital warts after infection with alpha genus human papillomavirus (HPV) types will provide important information for the design of prevention strategies. We conducted a cohort study of 18-21-year-old men who underwent triannual genital examinations. The 24-month cumulative genital wart incidence was 57.9% (95% confidence interval [CI], 38.1%-79.1%) among 46 men with incident detection of HPV-6 or HPV-11 infection, 2.0% (95% CI, 0.5%-7.9%) among 161 men with incident detection of infection with other HPV types, and 0.7% (95% CI, 0.2%-2.8%) among 331 men who tested negative for HPV. Our results suggest that genital warts are common after HPV-6 or HPV-11 infection in young men.