Demographics of study population.

<p>Demographics of study population.</p

Test performance characteristics.

<p>A. Crude estimates among women with full colposcopic and histologic evaluation (N = 675). B. Verification-biased adjusted estimates among total screened population (N = 2331).</p><p>CIN: cervical intraepithelial neoplasia, CI: confidence interval, PPV: positive predictive value, NPV: negative predictive value</p

Participation in screening and follow-up (colposcopy and biopsy where recommended) by randomization arm and screening result.

<p>Screen positive indicates positive result on VIA, Pap, and/or HPV DNA testing. Colposcopy normal indicates no area of abnormality identified, no biopsy recommended. Colposcopy abnormal-biopsy taken indicates that a biopsy was successfully obtained from all visually identified areas of abnormality. Colposcopically abnormal-biopsy refused indicates that a lesion was visualized and biopsy recommended, but the patient refused.</p

Estimated proportion of cases of CIN2+ observed and estimated via population weighting for verification bias adjustment.

<p><i>Screen detected</i> indicates proportion of cases of CIN2+ detected by hc2, and <i>screen undetected</i> indicates the proportion of CIN2+ cases detected through the screening program, but missed by hc2. <i>Refused biopsy</i> indicates the proportion of CIN2+ cases estimated among those who refused biopsy, <i>refused colposcopy</i> indicates the proportion of CIN2+ cases estimated among those who screened positive, but refused colposcopic exam, and <i>refused involvement</i> indicates the proportion of CIN2+ cases estimated among those who refused participation in the program (i.e., not screened).</p

Dense Genotyping of Immune-Related Loci Identifies Variants Associated with Clearance of HPV among HIV-Positive Women in the HIV Epidemiology Research Study (HERS)

<div><p>Persistent high-risk human papillomavirus (HR-HPV) is a necessary and causal factor of cervical cancer. Most women naturally clear HPV infections; however, the biological mechanisms related to HPV pathogenesis have not been clearly elucidated. Host genetic factors that specifically regulate immune response could play an important role. All HIV-positive women in the HIV Epidemiology Research Study (HERS) with a HR-HPV infection and at least one follow-up biannual visit were included in the study. Cervicovaginal lavage samples were tested for HPV using type-specific HPV hybridization assays. Type-specific HPV clearance was defined as two consecutive HPV-negative tests after a positive test. DNA from participants was genotyped for 196,524 variants within 186 known immune related loci using the custom ImmunoChip microarray. To assess the influence of each single-nucleotide polymorphism (SNP) with HR-HPV clearance, the Cox proportional hazards model with the Wei-Lin-Weissfeld approach was used, adjusting for CD4+ count, low risk HPV (LR-HPV) co-infection, and relevant confounders. Three analytical models were performed: race-specific (African Americans (n = 258), European Americans (n = 87), Hispanics (n = 55), race-adjusted combined analysis, and meta-analysis of pooled independent race-specific analyses. Women were followed for a median time of 1,617 days. Overall, three SNPs (rs1112085, rs11102637, and rs12030900) in the <i>MAGI-3</i> gene and one SNP (rs8031627) in the <i>SMAD3</i> gene were associated with HR-HPV clearance (p<10⁻⁶). A variant (rs1633038) in <i>HLA-G</i> were also significantly associated in African American. Results from this study support associations of immune-related genes, having potential biological mechanism, with differential cervical HR-HPV infection outcomes.</p> </div

Cox proportional Hazard Ratios (HR) for the SNPS associated with time to clearance of high-risk (HR-HPV) HPV infection in the race-adjusted analysis, individual race-specific analysis, and pooled analysis of the three races separately.

<p>Cox proportional Hazard Ratios (HR) for the SNPS associated with time to clearance of high-risk (HR-HPV) HPV infection in the race-adjusted analysis, individual race-specific analysis, and pooled analysis of the three races separately.</p

Manhattan plot showing the association P-values of single nucleotide polymorphisms (SNPs) in the ImmunoChip with the time to clearance of HR-HPV.

<p>The X-axes display the chromosome on which the SNP is located, the Y-axes display −log₁₀ P-value. The dashed black line represents a significance level needed for multiple testing using the K effective method. Panel A.) Race-adjusted analysis B.) African Americans only C.) European Americans only, and D.) Hispanics only.</p