Serum 25-hydroxyvitamin D level during early pregnancy and type 1 diabetes risk in the offspring.

AIMS/HYPOTHESIS: Vitamin D deficiency during the fetal period or infancy is one of the suggested environmental factors for type 1 diabetes and for its increasing incidence. To test this hypothesis we compared serum 25-hydroxyvitamin D (25(OH)D) levels during early pregnancy in mothers of children who subsequently developed type 1 diabetes (case mothers) with mothers of non-diabetic healthy children (control mothers) of the same age. METHODS: Children with type 1 diabetes were identified from the nationwide prescription register. 25(OH)D concentration was measured from serum samples collected during the first trimester of pregnancy from all Finnish women (Finnish Maternity Cohort). A total of 343 case mothers and 343 control mothers were included in the study. Samples were collected throughout the year. Samples from case and control mothers were matched on the day of collection. RESULTS: Mean 25(OH)D levels in case mothers (43.9 nmol/l) and control mothers (43.7 nmol/l) were not different. Of all mothers, 481 (70.1%) were vitamin D-deficient or -insufficient. CONCLUSIONS/INTERPRETATION: No difference was found in serum 25(OH)D concentrations during first trimester of pregnancy between mothers whose children later on developed type 1 diabetes, and mothers of non-diabetic ' healthy' children of the same age. It is difficult to detect possible effects of mothers' vitamin D deficiency during early pregnancy on the development of type 1 diabetes in the offspring in this population, as such a large proportion of mothers were vitamin D-deficient or -insufficient.

Chlamydia trachomatis seroprevalence atlas of Finland 1983-2003.

OBJECTIVES: To study Chlamydia trachomatis seroprevalence trends and geographical distribution over time in Finland. MATERIALS AND METHODS: First pregnancy serum samples were retrieved from the Finnish Maternity Cohort serum bank for the subcohort of 8000 women stratified by calendar years (1983-1989, 1990-1996, 1997-2003) and age at time of sample withdrawal (14-22 and 23-28 years). C trachomatis antibodies were determined using standard major outer membrane protein peptide ELISA. The spatiotemporal variation of C trachomatis seroprevalence rates was visualised by a series of maps. RESULTS: A decreasing C trachomatis seroprevalence trend from 1983 to 2003 was seen for both women under 23 years of age (20.8% to 10.6%) and 23-28-year-old women (19.1% to 12.5%). Constant clusters were seen around the largest cities and in eastern Finland although seroprevalence rates were generally decreasing throughout the country. CONCLUSIONS: Only a few population-based serological studies have been undertaken on C trachomatis epidemiology over time. In Finland the seroprevalence of C trachomatis is decreasing all over the country, albeit with small clusters remaining.

Population-based enrolment of adolescents in a long-term follow-up trial of human papillomavirus vaccine efficacy.

We evaluated a study setting for assessment of the long-term vaccine efficacy (VE) of human papillomavirus (HPV) virus-like-particle (VLP) vaccine against cervical carcinoma. A total of 22,412 16- to 17-year old adolescent women from seven cities in Finland were invited by letter to participate in a phase III study of a quadrivalent HPV (types 6, 11, 16, 18) VLP vaccine, between September 2002 and March 2003. A total of 30,947 18-year old women were invited to participate as unvaccinated controls. These women were asked about their willingness to participate in an HPV vaccination trial and to fill a health questionnaire. These three population-based cohorts of adolescent women, including women vaccinated with HPV vaccine or placebo vaccine and unvaccinated control women, are systematically followed over time. The study cohort database will be linked with the Finnish Cancer Registry using cervical carcinoma in situ (CIS) and invasive cervical carcinoma (ICC) as endpoints. Assuming that the cumulative incidence of CIS and ICC over 15 years is 0.45%, and that there is no loss to follow-up, and power of 80%, the determination of 70% total VE will require 3357 HPV vaccine recipients, 3357 placebo vaccine recipients, and 6714 unvaccinated controls. At the baseline, 2632 (12%) of the invited adolescents volunteered to the phase III vaccination trial, and 6790 (22%) responded to the questionnaire study. During a recruitment period of 10 months, 874 HPV vaccine recipients, 875 placebo recipients and 1919 unvaccinated controls were enrolled. Population-based enrollment of large cohorts of vaccinated and unvaccinated adolescents for passive registry-based follow-up with cervical carcinoma as the end-point is feasible and currently going on in Finland.

Prospective seroepidemiologic study of human papillomavirus infection as a risk factor for invasive cervical cancer.

BACKGROUND: Major risk factors for invasive cervical cancer include infection with human papillomavirus (HPV), infection with other sexually transmitted pathogens (e.g., Chlamydia trachomatis), and smoking. Since exposures to these risk factors can be related, the contribution of any single factor to cervical carcinogenesis has been difficult to assess. We conducted a prospective study to define the role of HPV infection in cervical carcinogenesis, with invasive cancer as an end point. METHODS: A nested case-control study within a joint cohort of 700,000 Nordic subjects was performed. The 182 women who developed invasive cervical cancer during a mean follow-up of 5 years were matched with 538 control women on the basis of age and time of enrollment. Serum samples taken at enrollment were analyzed for evidence of tobacco use (i.e., cotinine levels); for antibodies against HPV types 16, 18, and 33; and for antibodies against C. trachomatis. Relative risks (RRs) were estimated by use of conditional logistic regression. RESULTS: Presence of antibodies against HPV in serum (seropositivity) was associated with an increased risk of cervical cancer, and adjustment for smoking and for C. trachomatis seropositivity did not affect this finding (RR = 2.4; 95% confidence interval [CI] = 1.6-3.7). HPV16 seropositivity was associated primarily with an increased risk of squamous cell carcinoma (RR = 3.2; 95% CI = 1.7-6.2). In contrast, risk associated with HPV18 seropositivity tended to be higher for cervical adenocarcinoma (RR = 3.4; 95% CI = 0.8-14.9). In populations with a low prevalence of antibodies against C. trachomatis, the HPV16-associated risk of cervical cancer was very high (RR = 11.8; 95% CI = 3.7-37.0); in contrast, in populations with a high prevalence of antibodies against C. trachomatis, no excess risk was found. CONCLUSION: Past infection with HPV16 increases the risk of invasive cervical squamous cell carcinoma, most clearly seen in populations with a low prevalence of sexually transmitted diseases.

A prospective, seroepidemiological study of the role of human papillomavirus in esophageal cancer in Norway.

Infection with the human papillomavirus (HPV), notably HPV type 16, has been associated with esophageal cancer in seroepidemiological studies. To evaluate the consistency of the association, we performed a nested case-control study of HPV seropositivity and risk of esophageal cancer within a prospectively followed cohort of 300,000 Norwegian men and women who had donated blood samples to a serum bank. The data file of the serum bank was linked with the nationwide Cancer Registry of Norway to identify esophageal cancers diagnosed after donation of the serum sample. Fifty-seven cases and 171 matched controls were analyzed for antibodies to specific microorganisms, and odds ratios for developing esophageal cancer were calculated. There was an increased risk of developing esophageal cancer among HPV 16-seropositive subjects (odds ratio = 6.6; 95% confidence interval, 1.1-71) but not among Chlamydia trachomatis-seropositive subjects. Adjustment for the presence of serum cotinine, a marker of smoking habits, did not affect the estimates substantially. The seroepidemiological association between HPV 16 and esophageal cancer seems to be consistent in different countries.

Enterovirus infection as a risk factor for beta-cell autoimmunity in a prospectively observed birth cohort: the Finnish Diabetes Prediction and Prevention Study.

Previous studies suggest that enterovirus infections may initiate and accelerate beta-cell damage years before the clinical manifestation of type 1 diabetes. We have now analyzed the role of enterovirus infections in the initiation of autoimmunity in children who have tested positive for diabetes-associated autoantibodies in a prospective study starting at birth (the Finnish Diabetes Prediction and Prevention Study). The frequency of enterovirus infections was studied using both serology and testing for the presence of enterovirus RNA in the sera of 21 children who developed and retained autoantibodies and in 104 control subjects chosen from the same study cohort and matched for the time of birth, sex, and HLA alleles determining genetic diabetes susceptibility. Sample intervals were taken as basic units of follow-up, to which the observed number of infections was adjusted. Enterovirus infections were detected in 26% of sample intervals in the case subjects and in 18% of the sample intervals in the control children (P = 0.03). A temporal relationship between enterovirus infections and the induction of autoimmunity was found; enterovirus infections were detected in 57% of the case subjects during a 6-month follow-up period preceding the first appearance of autoantibodies compared with 31% of the matched control children in the same age-group (odds ratio 3.7, 95% CI 1.2-11.4). The frequency of adenovirus infections did not differ between the patient and control groups. Our data imply that enterovirus infections are associated with the development of beta-cell autoimmunity and provide evidence for the role of enteroviruses in the initiation of beta-cell destruction.

A prospective study of the role of coxsackie B and other enterovirus infections in the pathogenesis of IDDM. Childhood Diabetes in Finland (DiMe) Study Group.

Coxsackievirus B infections have been associated with clinical manifestation of insulin-dependent diabetes mellitus (IDDM) in several studies, but their initiating role in the slowly progressing beta-cell damage is not known. This is the first prospective study designed to assess the role of coxsackie B and other enterovirus infections in the induction and acceleration of this process. Three separate series were studied: 1) an intrauterine exposure series comprising 96 pregnant mothers whose children subsequently manifested IDDM and 96 control mothers whose children remained nondiabetic; 2) a cohort of 22 initially unaffected siblings of diabetic children who were followed until they developed clinical IDDM (mean observation time, 29 months) and 110 control siblings who remained nondiabetic; 3) a case-control series comprising 90 children with newly diagnosed IDDM and 90 control subjects. Enterovirus infections were identified on the basis of significant increases in serum IgG, IgM, or IgA class antibodies against a panel of enterovirus antigens (capture radioimmunoassay). Enterovirus antibodies were significantly elevated in pregnant mothers whose children subsequently manifested IDDM, particularly in cases in which IDDM appeared at a very young age, before the age of 3 years (P < 0.005). Serologically verified enterovirus infections were almost two times more frequent in siblings who developed clinical IDDM than in siblings who remained nondiabetic (mean, 1.0 vs. 0.6 infections/follow-up year; P < 0.001). This difference was seen both close to the diagnosis of IDDM and several years before diagnosis.(ABSTRACT TRUNCATED AT 250 WORDS)

Disease-associated antibodies in offspring of mothers with IDDM.

We studied 20 infants of mothers with IDDM participating in a pilot study for a dietary intervention trial, testing the hypothesis that avoidance of cow's milk proteins early in life will reduce the risk of subsequent IDDM. The aim was to evaluate the elimination of IDDM-associated antibodies from the peripheral circulation of the infants, the possible emergence of autoantibodies indicating beta-cell destruction, and the influence of the dietary intervention and genetic disease susceptibility on the development of these autoantibodies. Transplacentally transferred islet cell antibodies (ICAs) and antibodies to the 65-kDa isoform of glutamic acid decarboxylase (GAD65As) disappeared from the peripheral circulation of most infants over the first few months of life and in all infants before the age of 9 months. Insulin antibodies were eliminated before the same age in all cases but one. The higher the initial antibody level was, the longer the time required for elimination. Four infants tested positive for insulin autoantibodies (IAAs) on at least one occasion during the first year of life, and 5 out of 16 unaffected subjects (31%) had IAAs at the age of 2 years. One infant became positive for IAA before the age of 6 months, with increasing levels later, seroconverted to positivity for ICAs and GAD65As between 6 and 9 months and presented with clinical IDDM at the age of 14 months. He had the HLA DQB1*0302/x genotype, which predisposes carriers to IDDM, and had been given the casein hydrolysate formula as supplementary milk. There were no significant differences in the levels of various autoantibodies between two groups of subjects defined either on the type of dietary intervention or the degree of genetic susceptibility. The findings indicate that transplacentally transferred antibodies related to IDDM are usually eliminated from the peripheral circulation of infants before 9 months of age and that IDDM-associated autoantibodies may emerge before the age of 6 months. Our results also illustrate that avoidance of cow's milk proteins over the first 9 months of life does not provide total protection against IDDM.

High cardiovascular disease mortality in subjects with visual impairment caused by diabetic retinopathy.

OBJECTIVE: The aim of this study was to assess mortality and causes of death in subjects with visual impairment caused by diabetic retinopathy (DR). Only limited data are available concerning the mortality of subjects with DR, and to our knowledge, no data so far have been published on the mortality of subjects with visual impairment caused by DR. RESEARCH DESIGN AND METHODS: We identified 34 men and 73 women living in northern Finland with visual impairment caused by DR on 31 December 1993. The median age of the subjects was 71 years (range 27-88). The mortality of these 107 diabetic subjects was followed up for 4 years, until 31 December 1997, and compared with the mortality rates of 3 age- and sex-matched control groups. The first control group consisted of subjects treated for DR by laser coagulation from 1990 to 1993. The second control group consisted of diabetic subjects who had had fundus photographs taken from 1991 to 1992. The third control group comprised nondiabetic subjects selected from the population register. Information on deaths was obtained from official death certificates. RESULTS: A total of 91 diabetic and 10 nondiabetic subjects died during the follow-up. Of the deaths, 51 occurred in the subjects with visual impairment caused by DR, with a 4-year mortality rate of 477/1,000 (95% CI 382-571/1,000). Mortality rates were 224/1,000 (145-303/1,000) for the diabetic subjects with retinopathy treated by laser coagulation; 150/1,000 (82-217/1,000) for the diabetic subjects who had undergone fundus photography; and 94/1,000 (46-165/1,000) for the nondiabetic subjects. Cardiovascular diseases were the underlying cause of death in 55% of the subjects with visual impairment. Nephropathy was mentioned as the immediate cause of death for only 10% of the subjects. Compared with the nondiabetic control subjects, the odds ratios (ORs) for all-cause mortality were 5.1 (2.6-11) in the diabetic subjects with visual impairment caused by DR, and 5.6 (2.1-19) for mortality caused by diseases of the circulatory system. The ORs for all-cause mortality were 2.4 (1.1-5.6) in the diabetic subjects with retinopathy treated by laser coagulation and 1.6 (0.68-4.0) in the diabetic subjects with fundus photographs taken. CONCLUSIONS: The survival of diabetic subjects with visual impairment caused by DR was poor. The high mortality rate was attributed mainly to cardiovascular diseases. Therefore, severe retinopathy proves to be a risk marker of cardiovascular death in diabetic patients.

Joint effects of different human papillomaviruses and Chlamydia trachomatis infections on risk of squamous cell carcinoma of the cervix uteri.

This case-control study based in Nordic serum banks evaluated the joint effects of infections with genital human papillomavirus (HPV) types, and Chlamydia trachomatis in the aetiology of cervical squamous cell carcinoma. Through a linkage with the cancer registries, 144 cases were identified and 420 controls matched to them. Exposure to past infections was defined by the presence of specific IgG antibodies. The odds ratio (OR) for the second-order interaction of HPV16, HPV6/11 and C. trachomatis was small (1.0) compared to the expected multiplicative OR, 57, and the additive OR, 11. The interactions were not materially different among HPV16 DNA-positive squamous cell carcinomas. When HPV16 was replaced with HPV18/33 in the analysis of second-order interactions with HPV6/11 and C. trachomatis, there was no evidence of interaction, the joint effect being close to the expected additive OR. Possible explanations for the observed antagonism include misclassification, selection bias or a true biological phenomenon with HPV6/11 and C. trachomatis exposures antagonizing the carcinogenic effects of HPV16.

Hyperglycemia as a risk factor of mortality in a middle-aged Finnish population.

In 1990-1992, a population-based study was carried out in the city of Oulu in northern Finland, to assess the prevalence of diabetes mellitus (DM) and impaired glucose tolerance (IGT) in a middle-aged population. We report the mortality of the study population until 31 December 1998. Altogether 831 subjects (82%) (369 men) participated in the baseline examinations, in which the prognostic risk factors were determined. Special attention was given to the effect of hyperglycemia on mortality. The WHO 1985, ADA 1997 and WHO 1999 criteria for diabetes, IGT and impaired fasting glucose (IFG) were used. Forty-one subjects (32 men) died during the average follow-up of 6.7 years, and the mortality rate was hence 7.7/1000 person-years. The results suggest that both fasting and post-load hyperglycemia are important predictors of mortality. Estimated by the Cox proportional hazards regression, the unadjusted hazard ratio (HR) for death was 2.5 (95% CI 0.9-6.6) in the subjects classified as diabetic according to the WHO 1999 criteria compared to normoglycemic subjects. The corresponding HR of the subjects with IFG was 2.5 (95% CI 0.7-8.8) and that of the subjects with IGT 1.5 (0.6-3.7). In addition, a high mortality was predicted by smoking (HR 4.2, 95% CI 2.0-8.8), male gender (HR 3.5, 95% CI 1.6-7.9) and hypertension (HR 2.3, 95% CI 1.1-5.1).

Outcome of children after maternal primary Toxoplasma infection during pregnancy with emphasis on avidity of specific IgG. The Study Group.

Congenital toxoplasmosis results from maternal primary infection during pregnancy. In our serologic screening study 42 of 16,733 pregnant women had findings suggestive of primary infection. Here we document the outcome of their offspring, 37 of 39 liveborn children. After 12 months postnatally, serologically verified congenital toxoplasmosis appeared in 4 children. All these children had persisting IgG at the age of 12 months by both the dye test and the IgG enzyme-linked immunosorbent assay. All the congenitally infected infants had also specific IgM and IgA and showed significant increases in avidity of specific IgG during the 12-month follow-up. One of them had a unilateral retinal scar and intracranial calcifications. An additional 3 infants of the mothers with primary infection during early pregnancy presented with unilateral retinal scars but without seroresponses during the first 12 months of life. Maternal high avidity of IgG during the first trimester is a strong indicator against primary infection during pregnancy; the fetuses of such mothers are at low risk for congenital toxoplasmosis.

Human cytomegalovirus seroprevalence in three socioeconomically different urban areas during the first trimester: a population-based cohort study.

BACKGROUND: To re-evaluate the impact of socioeconomic status and human cytomegalovirus (HCMV) seroprevalence during pregnancy, we carried out a population-based cohort study. METHODS: IgG and IgM antibodies to HCMV and IgG avidity were studied by enzyme-linked immunosorbent assay (ELISA) in three different socioeconomic areas (SEA) in the 9-12th week of pregnancy of 1088 consecutive mothers. RESULTS: The overall IgG seropositivity was 70.7%, ranging from 60.9 to 76.4% in 'upper' to 'lower' SEA (P = 0.0004). The HCMV IgM seropositivity was 4.0%, ranging from 3.8% in the 'upper' and 'intermediate' SEA to 4.6% in the 'lower' SEA. Serologically acute cases, defined by low avidity of IgG, represented 1.7% of the pregnancies in the 'upper' SEA compared with 1.0 and 1.1% in the other two areas. In the 'lower' SEA there were twice as many recurrent infections as in the others, 3.6 versus 1.7%. The low impact of age did not increase after elimination of the effects of SEA and parity. Miscarriages were associated neither with IgG nor with IgM positivity, although the percentage of >/=2 miscarriages was 8.8% in seronegative women compared with 11.2% and 13.6% in IgG- and IgM-positive women. CONCLUSIONS: Social environment seems to be the most powerful factor, predicting both IgG seroprevalence and recurrences during pregnancy.

CT detection and location of intraorbital foreign bodies. Experiments with wood and glass.

The series comprises 27 patients examined by CT to detect, locate or exclude a foreign body. 22 of them actually had an orbital foreign body. In three cases CT was the primary method and showed the foreign body correctly, while in 18 it was first detected in plain films and CT was performed to locate it. 20 metallic foreign bodies were hyperdense in appearance. Two cases had wooden foreign bodies, one with a density of +10 HU and the other hypodense with a value of about -434 to -446 HU. The latter piece of wood was first interpreted falsely as a bubble of gas. The results proved that the detection of metal is easy, but differentiation between wood and gas is problematical. Experiments conducted to determine the CT densities of different pieces of wood gave results varying from -618 HU to +23 HU. The highest densities obtained for glass varied from +522 HU to +2000 HU. The density of a plastic lens was -105 HU.

Feeding and bedding materials as sources of microbial exposure on dairy farms.

Hay, grain, silage, and bedding are the sources of mold dust in agriculture. The aim of the present study was to evaluate the effect of different farming methods on exposure to airborne microbes. The study material comprised 50 silage, 54 hay, 47 grain, and 70 bedding samples taken on 18 farms in the beginning, middle, and end of the indoor feeding season. The modified wind-tunnel technique and six-stage impactors were used to determine the number of mesophilic bacteria, xerophilic fungi, mesophilic fungi, thermotolerant fungi, and thermophilic actinomycetes liberated from each material. Baled hay and straw liberated the largest amounts of microbes. Hay, except when dried in storage, liberated great numbers of fungal spores. The proportion of respirable airborne microbe-bearing particles was greatest in the highest concentrations. Theoretically, choosing the best possible alternative work methods could diminish exposure to microbes to one-tenth of the present level.

Candida immunity in patients undergoing surgical treatment for heart valve disease.

The appearance of Candida antigen (Latex agglutination method), Candida antibodies (indirect immunofluorescence) and positive fungal cultures as well as the lymphocyte transformation response to Candida antigen "in vitro" was studied in a series of 37 successive patients before and after heart valve replacement. The Candida antigen test was positive preoperatively in 11/36 (31%) and postoperatively in 14/36 (39%) of the patients and in 2/200 (1%) of the controls (blood donors). The differences in the frequencies of positive tests between the patient group and the control group are significant (p less than 0.001). The lymphocyte response to Oidiomycin (Candida albicans) preoperatively was greater than the mean control value in 6/11 (54.5%) of the patients showing a positive Candida antigen test, but only in 4/25 (16.0%) of the patients who were Candida antigen negative. The total number of lymphocytes and the number of ANAE positive (T) cells as well as the lymphocyte response to Oidiomycin (OID), tuberculoprotein (PPD) and phytohaemagglutinin (PHA) decreased markedly postoperatively. Candida antibody titres were positive (greater than or equal to 1:128) in 3/37 (8%) of the postoperative patients and in 2/84 (2.4%) of the controls. This difference is not significant. Positive Candida antibody titres were found postoperatively in 15/37 (41%) of the patients, which is a significantly higher frequency than that seen preoperatively (p less than 0.005). More positive fungal cultures from throat specimens (p less than 0.005) were found in the patient group before surgery than in the control group (hospital personnel). After surgery the number of positive fungal cultures in these cases decreased (p less than 0.001) due to the use of oral antifungal prophylaxis with nystatin tablets.(ABSTRACT TRUNCATED AT 250 WORDS)

Increase of syphilis in Finland related to the Russian epidemic.

In the early 1990s only 30 to 40 new serologically confirmed cases of syphilis were reported annually in Finland. Typical syphilis patients were heterosexual men who acquired the infection abroad. Since 1993, the incidence of syphilis has increased. In 19

Serum IgG antibody concentrations against environmental microbes in mares and foals during different seasons and effect of stabling practices.

Over periods of 22 and 14 months, IgG antibody concentrations in serum samples obtained monthly from 14 mares and 19 foals, respectively, were measured by use of ELISA against antigens of the following environmental microbes: Aspergillus umbrosus, Penicillium brevicompactum, Rhodotorula glutinis, Absidia corymbifera, Aspergillus fumigatus, Humicola grisea, Micropolyspora faeni, and Thermoactinomyces vulgaris. The mares and foals were on pasture from early June until early October, then were stabled during the winter season until the following June. In the mares, increased antibody concentrations against most microbes were observed typically in midwinter and late spring when the horses were stabled; antibody concentrations against R glutinis, however, peaked in August. Concentrations differed between the summer and winter seasons and, in most instances, between 2 consecutive years and correlated with amounts of rainfall during the previous harvest season. In the foals, circulating passively acquired antibodies disappeared within 3 to 4 months after birth. During the first year of life, substantially increased autogenous antibody concentrations were observed only against R glutinis. Antibody concentrations against the other microbes increased gradually toward the end of the indoor season. In a group of foals transferred indoors in autumn, 6 weeks later than the other foals, antibody concentrations were lower when measured in December. Results supported the view that, to minimize exposure to microbial spores during the winter season, horses should be kept outdoors as much as possible and attention should be focused on improving the ventilation in stables and the quality of feeds and beddings.

Serologically diagnosed infection with human papillomavirus type 16 and risk for subsequent development of cervical carcinoma: nested case-control study.

OBJECTIVE: To study human papillomavirus type 16 in the aetiology of cervical carcinoma. DESIGN: Within a cohort of 18814 Finnish women followed up to 23 years a nested case-control study was conducted based on serological diagnosis of past infection with human papillomavirus type 16. SUBJECTS: 72 women (27 with invasive carcinoma and 45 with in situ carcinoma) and 143 matched controls were identified during the follow up. MAIN OUTCOME MEASURE: Relative risk of cervical carcinoma in presence of IgG antibodies to human papillomavirus type 16. RESULTS: After adjustment for smoking and for antibodies to various other agents of sexually transmitted disease, such as herpes simplex virus type 2 and Chlamydia trachomatis, the only significant association was with infection with human papillomavirus type 16 (odds ratio 12.5; 95% confidence interval 2.7 to 57, 2P<0.001). CONCLUSION: This prospective study provides epidemiological evidence that infection with human papillomavirus type 16 confers an excess risk for subsequent development of cervical carcinoma.