Thomas E. Rohan

Epidemiology of Acquisition and Clearance of Cervical Human Papillomavirus Infection in Women from a High-Risk Area for Cervical Cancer

Acquisition and clearance of cervical human papillomavirus (HPV) infection were analyzed among 1425 low-income women attending a maternal and child health program in São Paulo, Brazil. Specimens collected every 4 months were tested by a polymerase chain reaction protocol (MY09/11). In all, 357 subjects were positive at least once. There were 1.3% new infections per month, with 38% cumulative positivity after 18 months. Of 177 positive subjects at enrollment, only 35% remained infected after 12 months. The monthly clearance rate was higher for nononcogenic types (12.2%; 95% confidence interval [CI], 9.6-15.4) than for oncogenic HPV infections (9.5%; 95% CI, 7.5-11.9). Median retention times were 8.1 months (95% CI, 7.8-8.3) for oncogenic types and 4.8 months (95% CI, 3.9-5.6) for nononcogenic HPV infections. The mean infection durations were 8.2 and 13.5 months for nononcogenic and oncogenic types, respectively. Although a womans age did not affect mean duration for oncogenic types (13-14 months), nononcogenic-type infections lasted longer (10. 2 months) among younger (<35 years old) than in older women (5.6 months).

Types of dietary fat and breast cancer: a pooled analysis of cohort studies.

Recently, there has been interest in whether intakes of specific types of fat are associated with breast cancer risk independently of other types of fat, but results have been inconsistent. We identified 8 prospective studies that met predefined criteria and analyzed their primary data using a standardized approach. Holding total energy intake constant, we calculated relative risks for increments of 5% of energy for each type of fat compared with an equivalent amount of energy from carbohydrates or from other types of fat. We combined study‐specific relative risks using a random effects model. In the pooled database, 7,329 incident invasive breast cancer cases occurred among 351,821 women. The pooled relative risks (95% confidence intervals [CI]) for an increment of 5% of energy were 1.09 (1.00–1.19) for saturated, 0.93 (0.84–1.03) for monounsaturated and 1.05 (0.96–1.16) for polyunsaturated fat compared with equivalent energy intake from carbohydrates. For a 5% of energy increment, the relative risks were 1.18 (95% CI 0.99–1.42) for substituting saturated for monounsaturated fat, 0.98 (95% CI 0.85–1.12) for substituting saturated for polyunsaturated fat and 0.87 (95% CI 0.73–1.02) for substituting monounsaturated for polyunsaturated fat. No associations were observed for animal or vegetable fat intakes. These associations were not modified by menopausal status. These data are suggestive of only a weak positive association with substitution of saturated fat for carbohydrate consumption; none of the other types of fat examined was significantly associated with breast cancer risk relative to an equivalent reduction in carbohydrate consumption.

Type-Specific Duration of Human Papillomavirus Infection: Implications for Human Papillomavirus Screening and Vaccination

BACKGROUND Understanding the duration of human papillomavirus (HPV) infection may help find suitable end points for vaccine trials and testing intervals in screening studies. We studied genotype-specific infection duration among 2462 women enrolled in the Ludwig-McGill cohort study. METHODS Cervical specimens collected every 4-6 months were tested by a polymerase chain reaction protocol. Actuarial techniques were used to estimate the duration of HPV infection and to investigate the influence of age, number of sexual partners, and coinfection with multiple HPV types. RESULTS At enrollment, the prevalence of infection with high-risk HPV types was 10.6%, and the prevalence of infection with low-risk HPV types was 6.1%; incidence rates were 6.1 and 5.0 infections per 1000 women-months, respectively. Prevalent infections took longer to clear than incident infections (mean time to clearance, 18.6 months vs. 13.5 months). The mean duration of incident infection with high- and low-risk HPV varied according to the analytic approach used to measure this variable and showed considerable variation by HPV type (range, 5.1-15.4 months). Age and number of partners did not influence infection duration, whereas coinfection was associated with increased infection duration. The mean duration of HPV-16 monoinfection was 11.0 months, and the mean duration of HPV-16 coinfection was 15.4 months. CONCLUSION There was considerable variation among HPV types with regard to the duration of infection. Coinfection with multiple types contributed to an increased infection duration.

Accuracy of short-term recall of age at menarche

This study was conducted as part of the third annual follow-up of a cohort of 657 girls to test the accuracy of short-term recall of age at menarche. During the first and second annual follow-ups of the cohort, 101 girls had reported menarche. We sent questionnaires to these subjects at the third annual follow-up and asked them to recall the month and year of their menarche. Eighty-eight respondents returned their questionnaires with the relevant information. Overall, 59.1% of the respondents were able to recall their menarche with the exact month and year. The mean recall interval was 430 days. When the data were grouped by the interval of recall, higher accuracy was observed with a shorter interval of recall. With a mean interval of recall of 323 days, 66.1% of the subjects were able to recall their menarche correctly, whereas with a mean interval of 649 days, only 44.8% of the subjects were able to recall correctly.

Dietary factors and survival from breast cancer

The association between self-reported intake of various dietary factors at diagnosis and survival from breast cancer was studied in a population-based cohort of breast cancer patients in Adelaide, South Australia. These patients had been recruited between 1982 and 1984 into a case-control study of diet and incident breast cancer. Of the 451 patients recruited originally, 412 were followed for a median interval of 5.5 years. There were decreases in the risk of death from breast cancer ranging from 25 to 40% at all levels of energy and protein intake above the baseline, whereas for fat intake there was a 40% increase in risk at the uppermost quintile level. There was also some reduction in risk at the upper levels of intake of beta-carotene and vitamin C. However, there were no dose-dependent variations in risk of death by level of intake for any of the dietary factors studied, and most of the variation in risk that was observed was relatively insubstantial.

A cohort study of nutritional factors and endometrial cancer.

To evaluate the role of nutritional factors in the etiology of endometrial cancer, we performed a case-cohort analysis using data from women enrolled in the National Breast Screening Study in Canada from 1980 to 1985. For this analysis, a subcohort was constructed by selecting a 10% random sample from the 56,837 women in the dietary cohort. Cases were the 221 women diagnosed with incident adenocarcinoma of the endometrium during follow-up to December 31, 1993 and ascertained by record linkage to the Canadian Cancer Database. Information on usual diet at enrolment and other epidemiological variables was collected by means of self-administered questionnaires. Hazard ratios were obtained from proportional hazards regression models, with estimation of robust standard errors. We found a strong association of endometrial cancer with body mass index >25 kg/m2 (hazard ratio 2.72, 95% CI: 2.06–3.50). Endometrial cancer risk was not associated significantly with intakes of total energy, carbohydrates, proteins, total fat and major fatty acids, total dietary fiber and various types of fibers, vitamin C, E and A, folic acid, β-carotene, lutein, or cryptoxanthin. Some decrease in risk was noted with relatively high intakes of saturated fat, animal fat or lycopene. The associations observed in the study were independent of total energy intake and most non-dietary risk factors. The study suggests that dietary intakes of energy and most major nutrients are not related to the risk of endometrial cancer among Canadian women.

A Review Of Physical Activity And Breast Cancer

Breast cancer risk is influenced by endogenous hormones. Physical activity may offer one means for the primary prevention of breast cancer through its influence on ovarian hormones. This influence is manifested by changes in age at menarche and the number and nature of ovulatory menstrual cycles, factors that themselves are related to breast cancer risk. Animal experimental studies show that breast cancer risk is decreased by exercise at the time of tumor initiation but not necessarily by exercise during tumor promotion. Epidemiologic studies indicate, overall, a decreased risk of breast cancer among those women who are more physically active, whereas experimental studies of the effects of exercise in women have shown that exercise can influence characteristics of the menstrual cycle. Nevertheless, the experimental studies in women and epidemiologic studies of physical activity and breast cancer risk have been hampered by a number of methodologic limitations. The major problems in the epidemiologic studies include crude and incomplete measurements of physical activity over a womans lifetime and inadequate control for potential confounding factors. Experimental studies of the effects of physical activity on menstrual activity in women have not adequately quantified the intensity of activity and the resultant effects on menstrual cycle changes.

Design and methods of the Ludwig-McGill longitudinal study of the natural history of human papillomavirus infection and cervical neoplasia in Brazil

This article reports on a large longitudinal study, begun in 1993, of the natural history of human papillomavirus (HPV) infection and cervical neoplasia in a population of low-income women in São Paulo, Brazil, a city with one of the highest risks worldwide for cervical cancer. Known as the Ludwig-McGill cohort study, the epidemiological investigation focuses on persistent infection with oncogenic HPV types as the precursor event leading to cervical neoplasia. The objectives of this study are to: 1) study the epidemiology of persistent cervical HPV infection in asymptomatic women, 2) investigate whether persistent HPV infection increases risk of low-grade and high-grade cervical lesions, 3) search for determinants of persistent HPV infection, 4) search for molecular variants of HPV that may be associated with an increased risk of lesions, 5) investigate whether viral burden is correlated with persistent infections and with lesion risk, 6) study the antibody response to HPV as a predictor of persistence and lesion progression, and 7) examine the role of HLA typing and codon 72 p53 gene polymorphism in mediating HPV persistence and lesion severity. The study accrued 2,528 female subjects through March 1997. Subjects were followed up every 4 months in the first year, with twice-yearly return visits to take place in subsequent years. Participants undergo a questionnaire-based interview, have a cervical specimen taken for Pap cytology and HPV testing, and have a blood sample drawn for HPV antibody testing. A cervicography is performed once in the first year and every two years thereafter. In this article we describe the design and methods of the study, provide baseline cohort characteristics, and present a preliminary assessment of the prognostic value of baseline HPV status.

Dietary intake of selected B vitamins in relation to risk of major cancers in women

Although folic acid has been investigated for its potential to inhibit carcinogenesis, few epidemiologic studies have assessed the effects of intake of thiamin, riboflavin, and niacin, which may reduce cancer risk by acting as cofactors in folate metabolism or by other mechanisms. Using data from a large cohort of Canadian women, we examined the association of dietary intake of these nutrients, as well as intake of folate, methionine, and alcohol, with cancers of the breast, endometrium, ovary, colorectum, and lung ascertained during an average of 16.4 years of follow-up. After exclusions, the following numbers of incident cases were available for analysis: breast, n=2491; endometrium, n=426; ovary, n=264; colorectum, n=617; and lung, n=358. Cox proportional hazard models were used to estimate risk of each cancer with individual nutrients and to explore possible effect modification by combinations of nutrients on cancer risk. Few significant associations of intake of individual B vitamins with the five cancers were observed. Alcohol consumption showed a modest positive association with breast cancer risk but not with risk of the other cancers. There was no evidence of effect modification among the nutrients. This large study provides little support for an association of dietary intake thiamin, riboflavin, niacin, folate, or methionine with five major cancers in women.

Nutritional factors and prostate cancer: a case-control study of French Canadians in Montreal, Canada

The relationship between the risk of prostate cancer and dietary intake of energy, fat, vitamin A, and other nutrients was investigated in a case-control study conducted in Montreal (Quebec), Canada. French Canadians aged 35 to 84 years with a recent, histologically confirmed diagnosis of adenocarcinoma of the prostate were identified through the admission offices of five major francophone teaching-hospitals in Montreal from 1989 to 1993. Population-based controls matched for age (±five years), language, and place of residence were selected by a modified random-digit dialing method. The study included 232 cases and 231 controls. Information on dietary intake was collected by means of a quantitative dietary history. No association was evident between energy intake and the risk of prostate cancer. In contrast, there was some evidence of an inverse association with intake of total fat, animal fat, monounsaturated fat, and particularly saturated fat (odds ratio = 0.69, 95 percent confidence interval = 0.40–1.18, P=0.05), while a nonsignificant positive association was found with polyunsaturated fat. In addition, high intake of retinol and vegetable protein (highest cf lowest quartile) was associated with reduced risk, but was not statistically significant. No associations were established between intake of other nutrients and risk. These patterns persisted after adjustment for a number of potential confounding factors.