Background: Persistent Human Papillomavirus (HPV) is an etiologic agent in the development of cervical cancer. Despite the increasingly high prevalence of HPV, people at risk of exposure lack knowledge about the virus, its relationship to cervical cancer, and a realistic perspective regarding HPV consequences. Purpose: To describe knowledge about HPV with particular emphasis on behavioral risk and experience with HPV and an abnormal Pap smear. Methods: A 36-item Internet survey was developed which included a 14-item knowledge composite (HPVAPK), a behavioral risk composite, and an experience composite. The independent variables examined were gender, HPV-risk behavior, and experience. The dependent variable (HPVAPK) was a knowledge-composite that addressed HPV and abnormal Pap smears. Results: Among the students (n= 492) who completed the Internet survey, females with higher risk behavior and those with a history of an abnormal Pap were more knowledgeable than males, those with lower risk behavior, and those with indirect experience, or no experience with the topic. However, even those with the highest knowledge scores exhibited a low level of knowledge regarding particular HPV issues. Discussion: Not only did this study reveal a low level of knowledge about HPV and abnormal Pap smears, it revealed particular topics that are misunderstood about HPV and the diagnosis of an abnormal Pap smear-even among women who have experience with an abnormal Pap smear. Translation to Health Education Practice: The issues highlighted should be included when discussing HPV and abnormal Pap smears with both males and females within small educational forums such as health education classes, and student health visits.

Human papillomavirus (HPV), the primary cause of cervical cancer, is also associated with the development of anal cancer. Relatively little is known about the epidemiology of anal HPV infection among healthy females and its relationship to cervical infection. We sought to characterize anal HPV infection in a cohort of adult women in Hawaii. Overall, 27% (372 of 1,378) of women were positive for anal HPV DNA at baseline compared with 29% (692 of 2,372) with cervical HPV DNA. Among women with paired anal and cervical samples, anal infection without accompanying cervical infection was observed in 14% (190 of 1,363). Concurrent anal and cervical HPV infections were observed in 13% (178 of 1,363) of women. Women with cervical HPV infection had >3-fold increased risk of concurrent anal infection. Concurrent anal and cervical HPV infection was most prevalent among the youngest women and steadily decreased through age 50 years. By contrast, the prevalence of anal infection alone remained relatively steady in all age groups. Compared with cervical infections, the overall distribution of HPV genotypes in the anus was more heterogeneous and included a greater proportion of nononcogenic types. A high degree of genotype-specific concordance was observed among concurrent anal and cervical infections, indicating a common source of infection. Nevertheless, the association of anal intercourse with anal HPV infection was limited to those women without accompanying cervical infection. The relationship of anal to cervical infection as described in this study has implications for the development of anal malignancies in women.

Epidemiological studies have been inconsistent regarding a role for folate in the etiology of cervical dysplasia. Methylenetetrahydrofolate reductase (MTHFR) catalyzes the synthesis of 5-methyltetrahydrofolate, which is involved in the methylation of homocysteine to methionine. A common variant of this enzyme, resulting from a 677C-->T (Ala-->Val) substitution in the gene, has been shown to have reduced activity and is associated with mild hyperhomocysteinemia. A multiethnic case-control study was used to examine the association of dietary folate and MTHFR genotype with the odds ratios (ORs) for cervical dysplasia among women identified from several clinics on Oahu, Hawaii, between 1992 and 1996. We collected blood samples for DNA extraction, cervical smears for cytological diagnosis, exfoliated cervical cells for human papillomavirus (HPV) DNA testing, and personal interviews from 150 women with squamous intraepithelial lesions (SILs) and from 179 women with cytologically normal (Pap) smears. We found a positive, monotonic trend (P = 0.02) in the ORs for cervical SILs associated with the number of variant MTHFR T alleles, after multivariate adjustment. Women with the heterozygous CT genotype had twice the risk of cervical SILs [OR, 2.0; 95% confidence interval (CI), 1.1-3.7], and women with the homozygous TT genotype had almost three times the risk of SILs (OR, 2.9; 95% CI, 1.0-8.8) compared to women with the homozygous MTHFR CC genotype. The dietary intakes of folate, vitamin B(6), and vitamin B(12) were inversely related to the ORs for cervical SILs, after adjustment for HPV DNA and other confounders. The OR among women in the highest quartile compared with women in the lowest quartile of folate intake was 0.3 (95% CI, 0.1-0.7; P for trend = 0.002). Women with the variant T allele and folate intakes below the median were at significantly elevated risk of cervical SILs (OR, 5.0; 95% CI, 2.0-12.2) compared to women with CC alleles and folate intakes above the median. HPV infection was a strong risk factor for cervical dysplasia, particularly among women with the variant T allele (OR, 46.6; 95% CI, 15.9-136.2). All associations of MTHFR genotype with the ORs for cervical SILs were independent of other risk factors under study. These findings suggest that the MTHFR T allele and reduced dietary folate may increase the risk for cervical SILs.

OBJECTIVE:In this investigation, we explored the hypothesis that genetic polymorphisms in the cytochrome P4501A1 (T3801C) and glutathione S-transferase classes mu and theta (GSTM1 and GSTT1) gene deletions promote the development of cervical dysplasia by moderating the activation and detoxification of polycyclic hydrocarbons and other compounds that influence oxidative stress and DNA adduct formation.METHODS:A multiethnic, case-control study of 131 women with biopsy-confirmed cervical squamous intraepithelial lesions (SIL) and 180 controls with cytologically normal cervical (Pap) smears was conducted between 1992 and 1996 in Honolulu, Hawaii. We collected in-person interviews, a blood sample to extract genomic DNA, and an exfoliated cervical cell sample to determine the presence and type of human papillomavirus (HPV) using PCR dot-blot hybridization. Genotyping for the CYP1A1 MspI allelic variant and deletion of the GSTM1 and GSTT1 gene loci followed a PCR method.RESULTS:Women who were homozygous, but not heterozygous, for the CYP1A1 MspI variant allele were at significantly increased risk of cervical SIL (odds ratio (OR) = 3.4; 95% confidence interval (CI) = 1.1-10.7) compared to women who were homozygous for the wild-type allele. Subjects with the GSTM1 null genotype had a nonsignificant elevated risk of cervical SIL (OR = 1.6; 95% CI = 0.8-3.0) compared to women with the gene present. No difference in the risk of cervical disease was associated with the GSTT1 null genotype. The combination of the CYP1A1 homozygous variant and the GSTM1 null genotypes increased the odds ratio for cervical SIL to 5.1 (95% CI = 1.3-20.7). There was no evidence for an interaction between genotype and exposure to tobacco smoke, alcohol drinking, or HPV DNA positivity.CONCLUSIONS:These findings, although based on a small number of subjects, suggest that the CYP1A1 MspI polymorphism may be a susceptibility factor for early, premalignant changes in the cervical epithelium.

Little is known about factors that favor the development of cervical atypical squamous cells of undetermined significance (ASCUS), nor how these factors might affect the pathogenesis of cervical neoplasia. The primary focus of this case-control study among the multiethnic population of Hawaii was to identify biomarkers of diet in the recent past that may influence the risk of ASCUS, after carefully accounting for the presence of HPV DNA. Cases included 185 women with ASCUS and 191 cytologically-normal controls diagnosed between 1992 and 1996 from three clinics in Honolulu, Hawaii. In-person interviews were conducted in the subjects' homes, a fasting blood sample was drawn to measure plasma levels of various micronutrients, and the presence and type of HPV was determined in exfoliated cell samples using Polymerase Chain Reaction (PCR) dot blot hybridization. As results, we found an inverse dose-response gradient with increasing plasma concentrations of &mgr;-cryptoxanthin and &mgr;-tocopherol for the development of ASCUS. The odds ratio for ASCUS among women in the highest quartile compared with women in the lowest quartile of total cryptoxanthin was 0.5 (95% confidence interval (CI): 0.3-1.0), &mgr;-cryptoxanthin was 0.4 (0.2-0.8), total tocopherol was 0.5 (0.2-1.0), &mgr;-tocopherol was 0.5 (0.2-1.0), and &mgr;-tocopherol was 0.4 (0.2-0.8). Little association of plasma levels of lutein/zeaxanthin, lycopene, &mgr;- or &mgr;-carotene, retinol, vitamin C, or cholesterol, with disease risk was evident. Our findings suggest that women with high circulating concentrations of cryptoxanthin and tocopherol may be at a reduced risk of ASCUS.