Cosette M. Wheeler

Determinants of genital human papillomavirus infection among cytologically normal women attending the University of New Mexico student health center.

OBJECTIVES To confirm the risk factors for genital human papillomavirus (HPV) infection. GOAL OF THIS STUDY To investigate risk factors for HPV detection apart from the correlated risk factors for cervical neoplasia. STUDY DESIGN Cervical human papillomavirus (HPV) DNA was assessed in 357 cytologically normal women attending the University of New Mexico student health center. Cervical swab samples were obtained for HPV DNA detection and typing using a PCR-based DNA amplification system. Possible determinants of cervical HPV were examined including age, ethnicity, history of sexually transmitted disease, oral contraceptive use, smoking, age at first intercourse, lifetime number of sex partners, marital status, and history of pregnancy. RESULTS A 44.3% overall prevalence of cervical HPV was observed. On univariate analysis, factors associated with increasing HPV prevalence included higher lifetime number of sex partners and single marital status. After adjustment for potential confounding variables, we found that HPV prevalence increased with higher lifetime number of sexual partners. CONCLUSION These findings, along with those from the companion reports in this issue of the journal, support the sexual route of transmission of the virus.

The Clinical Meaning of a Cervical Intraepithelial Neoplasia Grade 1 Biopsy

OBJECTIVE: To determine whether the diagnosis of cervical intraepithelial neoplasia (CIN) grade 1 increases the risk of CIN 3 above what is observed for human papillomavirus (HPV) infection. METHODS: Using data from the atypical squamous cells of undetermined significance (ASCUS) and low-grade squamous intraepithelial lesions (LSIL) triage study, we compared the 2-year cumulative risk of CIN 3 for women with an enrollment diagnosis of CIN 1 (n=594) (median age 23 years) compared with those with negative histology or no biopsy taken at colposcopy (“no CIN 1,” n=570) (median age 24 years). Baseline cervical specimens were tested for carcinogenic HPV by a clinical HPV test and HPV genotypes by polymerase chain reaction. Logistic regression was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs) as a measure of association of enrollment status, including CIN 1 compared with no CIN 1 diagnosis, with 2-year worst outcomes of CIN 3. RESULTS: The two-year risks of CIN 3 were 10.3% (95% CI 7.9–13.0) for women with CIN 1, 7.3% (95% CI 4.6–10.9) for negative histology, and 6.4% (95% CI 3.8–9.9) for women referred to colposcopy and no biopsies were taken (P=.1). The 2-year risks of CIN 3 for women positive for HPV16, HPV18, or other carcinogenic HPV genotypes were 19.1%, 13.9%, and 5.7%, respectively, and did not differ significantly by the baseline cytology interpretation (ASCUS or LSIL). Taking HPV genotypes into account, having a CIN 1 (compared with no CIN 1) was not a risk factor for developing CIN 3 (OR 0.99, 95% CI 0.54–1.8). CONCLUSION: A CIN 1 diagnosis does not represent a significant risk factor for CIN 3 above the risk attributed to its molecular cause, genotype-specific HPV infection. LEVEL OF EVIDENCE: II

Risk of HPV-16/18 Infections and Associated Cervical Abnormalities in Women Seropositive for Naturally Acquired Antibodies: Pooled Analysis Based on Control Arms of Two Large Clinical Trials

Background Studies on the role of antibodies produced after infection with human papillomavirus 18 (HPV-18) and subsequent protection from HPV-18 infection have been conflicting, mainly due to inadequate sample size. Methods We pooled data from the control arms of the Costa Rica Vaccine Trial and the PATRICIA trial. Using Poisson regression we compared the risk of newly detected 1-time HPV-18 infection, HPV-18 1-year persistent infection (12MPI), and HPV-18-associated atypical squamous cells of undetermined significance or greater (ASC-US+) lesions between HPV-18 seropositive and seronegative women. Results High HPV-18 antibodies at enrollment was associated with reduced subsequent HPV-18 detection (P trend = 0.001; relative rate [RR] = 0.69; 95% confidence interval [CI], 0.47-1.01 for the third quartile; RR = 0.63; 95% CI, 0.43-0.94 for the fourth quartile, compared to seronegative). The risk of 12MPI showed a decreasing trend with increasing antibodies (P trend = 0.06; RR = 0.72; 95% CI, 0.29-1.77; RR = 0.42; 95% CI, 0.13-1.32 for the third and fourth quartiles, respectively). Lastly, we observed a significant decreased risk of HPV-18 ASC-US+ with increasing antibody (P trend = 0.01; RR = 0.46; 95% CI, 0.21-0.97 for the fourth quartile). We also observed a significant decreased risk of HPV-16 infection, 12MPI, and ASC-US+ with increasing HPV-16 antibody level. Conclusions High HPV-18 naturally acquired antibodies were associated with partial protection from future HPV-18 infections and associated lesions. Clinical Trials Registration NCT00128661 and NCT001226810.