Human Papillomavirus Cofactors by Disease Progression and Human Papillomavirus Types in the Study to Understand Cervical Cancer Early Endpoints and Determinants

Abstract

Human papillomavirus (HPV) cofactors for cervical cancer include smoking, multiparity, and oral contraceptive use, but their mechanisms of action are not fully understood. It is also unknown whether cofactors vary by HPV genotypes. The Study to Understand Cervical Cancer Early Endpoints and Determinants (SUCCEED) is a cross-sectional study comprising women referred to the University of Oklahoma from November 2003 to September 2007 for abnormal cervical screening results. Detailed questionnaire data and liquid cytology specimens were collected and the latter was genotyped for HPV using the LINEAR ARRAY HPV Genotyping Test. The present analysis includes women with both questionnaire and HPV data and diagnosed with <CIN1 (n = 535), CIN1 (n = 497), CIN2 (n = 336), CIN3 (n = 292), and cancer (n = 80). We evaluated HPV types and cofactors among HPV-infected women by calculating odds ratios (OR) and 95% confidence intervals (95% CI) for CIN3 and CIN2 separately compared with <CIN2 using a polytomous logistic regression model; cancers were excluded from further analysis due to the substantially higher ages of these women. We found that HPVinfected women with minor histologic or cytologic abnormalities (e.g., CIN1, ASCUS, and LSIL) were indistinguishable from those with normal histology/ cytology and were thus combined to form the referent group (<CIN2). Among women positive for oncogenic HPV, current smokers had a 2.5-fold increased risk for CIN3 (95% CI, 1.8-3.6) compared with nonsmokers. Among HPV16-infected women, current smokers had elevated risk for both CIN2 (OR, 1.9; 95% CI, 1.1-3.2) and CIN3 (OR, 2.7; 95% CI, 1.6-4.6). Our data suggest that non-HPV16-related CIN2 likely reflects a combination of CIN1 and CIN3 diagnosis, whereas HPV16-related CIN2 may indicate a precancerous state. Investigations on the molecular distinctions along the disease continuum of cervical pathogenesis by HPV type are needed. (Cancer Epidemiol Biomarkers Prev 2009;18(1):113 -20)

Local immune response in the microenvironment of CIN2–3 with and without spontaneous regression

“…[25][26][27] In agreement with this, all the analyzed CIN2-3 lesions were infiltrated by various numbers of adaptive immune cells like CD138 þ B-lymphocytes, CD8 þ cytotoxic T-lymphocytes and CD4 þ helper T-lymphocytes. Adaptive immune cells can recognize and specifically act against the E6 and E7 antigens expressed by HPV-infected cells 28 to clear the infection.…”

APOBEC3A Functions as a Restriction Factor of Human Papillomavirus

“…A. den Boona, M. Horswilla, Z. Wang, S. Hewitt, M. Schiffman, M. Sherman, R. Zuna, J. Walker, S. S. Wang, M. A. Newton, P. F. Lambert, N. Wentzensen, and P. Ahlquist, unpublished data). This study was performed by using 128 fresh-frozen cervical tissue samples under the Study To Understand Cervical Cancer Early Endpoints and Determinants (SUCCEED), as previously described (52). To determine gene expression patterns of APOBEC family members during cervical cancer progression, we analyzed this gene expression data set and found significantly higher hA3A and hA3B mRNA expression levels in low-and high-grade lesions than in normal tissue ( Fig.…”

Human Papillomavirus Load Measured by Linear Array Correlates with Quantitative PCR in Cervical Cytology Specimens

“…Prior to colposcopic examination, cervical cell samples were collected and rinsed directly into PreservCyt solution (Hologic, Boxborough, MA) as previously described (16 , and CP6108). The procedure followed recommendations of the manufacturer with the following variations: 10 l of template DNA was amplified and the amplified products were hybridized and detected using an automated Auto-LiPA staining system using 2.5 ml of each reagent per strip (compared to 3.0 ml in manual processing), as previously described (17).…”