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Joakim Dillner

Publications and source records attributed to Joakim Dillner.

At least 55 records · Page 3Linked to original sources

Evaluation of antibody response to human papillomavirus early proteins in women in whom cervical cancer developed 1 to 20 years later.

OBJECTIVE: Infection with oncogenic human papillomaviruses (HPVs) is the most important cause of cervical cancer worldwide. After infection there is a long latency period of at least 10 to 15 years during which cervical cancer develops in a small proportion of originally infected women. Up to 50% of these women have at diagnosis antibodies to the HPV oncoproteins E6 and E7, which are rarely found among healthy women. Our purpose was to evaluate whether antibodies to HPV16 and HPV18 E6 and E7 proteins are useful for early diagnosis of cervical cancer by measuring the antibody response in women in whom cervical cancer later developed. STUDY DESIGN: A joint serum bank of 550,000 Swedish, Norwegian, and Finnish women was followed up for 0.5 to 20 years, after which 178 invasive cervical carcinoma (ICC) cases, 150 of whom had squamous cell carcinoma (SCC), and 527 controls were identified. Antibodies to HPV16 and HPV18 E6 and E7 proteins were determined by tag enzyme-linked immunoassays. RESULTS: HPV16/18 E6 and E7 antibodies were detected infrequently (7.0%) in women in whom SCC later developed and yielded a moderately increased estimate of associated relative risk (odds ratio 2.7, 95% CI 1.1-6.4). Sensitivity of the combined antibody tests for the detection of occult SCC varied between 6% and 14% but was not related to time lag between serum sampling and cancer diagnosis. CONCLUSION: HPV16/18 E6 and E7 antibody responses are not sensitive markers of occult cervical cancer.

Adult↗

Serum antibody response to the heat shock protein 60 of Chlamydia trachomatis in women with developing cervical cancer.

OBJECTIVE: The purpose of this study was to determine whether serum antibody response to the three versions of chlamydial heat shock protein 60 is associated with an increased risk for cervical cancer. STUDY DESIGN: Women with cervical carcinoma were identified by linking the data files of three Nordic serum banks with cancer registries. Overall, 178 women with invasive cervical carcinoma were identified. For each case, the earliest prediagnostic serum sample was chosen, and three matched control subjects who were free of cancer at the time of the case diagnosis were selected randomly. Serum antibodies to the chlamydial heat shock protein 60 were measured by enzyme-linked immunosorbent assay and correlated with the risk of the subsequent development of cervical cancer. RESULTS: Antibodies to chlamydial heat shock protein 60-1 were associated with cervical squamous cell carcinoma among cases with long lag time (>3.5 years; odds ratio, 2.4; 95% CI, 1.1-5.1). Antibodies to chlamydial heat shock protein 60-2 or chlamydial heat shock protein 60-3 were not associated with cervical cancer risk. CONCLUSIONS: The finding that chlamydial heat shock protein 60-1 antibodies are associated with an increased cervical cancer risk suggests that persistent Chlamydia trachomatis infection may contribute to cervical neoplasia.

Antibodies↗

Seroepidemiology of the human polyomaviruses.

To assess the stability of polyomavirus antibodies in serial samples over time and the incidence and age-specific prevalence of polyomavirus infections, we established enzyme immunoassays (EIAs) using purified yeast-expressed virus-like particles (VLPs) containing the VP1 major capsid proteins of JC virus (JCV) and the AS and SB strains of BK virus (BKV). A random subsample of 150 Finnish women who had serum samples taken during the first trimester of pregnancy and had a second pregnancy during a 5 year follow-up period was selected, grouped by age of first pregnancy. The polyomavirus antibody levels were similar in samples taken during the first and second pregnancies (correlation coefficient 0.93 for BKV SB and 0.94 for JCV). Analysis of serum samples from 290 Swedish children aged 1-13 years, grouped by age in 2 year intervals, demonstrated that BKV seropositivity increased rapidly with increasing age of the children, reaching 98 % seroprevalence at 7-9 years of age, followed by a minor decrease. JCV seroprevalence increased only slowly with increasing age and reaching 72 % positivity among mothers >25 years of age. The age-specific seroprevalence of the human polyomaviruses measured using this VLP-based EIA was similar to previous serosurveys by other methods. The stability of the antibodies over time indicates that polyomavirus seropositivity is a valid marker of cumulative virus exposure, and polyoma VLP-based EIAs may therefore be useful for epidemiological studies of these viruses.

Adolescent↗

Time trends in incidence and prevalence of human papillomavirus type 6, 11 and 16 infections in Finland.

Human papillomavirus (HPV) type 16 is the major cause of cervical carcinoma, the incidence of which is decreasing in western countries. In Finland the incidence is, however, increasing in women aged <40 years, but possible underlying changes in HPV-16 epidemiology are unknown. To assess incidence trends of HPV infections, paired sera from a random sample of 8000 women with two pregnancies/sera within 5 years, taken from the serum bank of the Finnish Maternity Cohort (1983-98), were analysed for HPV-6, -11 and -16 antibodies. For 23-31-year-old women, HPV-16 incidence increased over the period 1983-97. HPV-16 seroprevalence increased from 17% in 1983-85 to 24% in 1995-97, but HPV-6 and HPV-11 prevalence was stable at 9-12% throughout the study period. Epidemic spread of the oncogenic HPV-16, but not the non-oncogenic HPV-types, throughout the 1980s and 1990s preceded an increase in the incidence of cervical carcinoma in fertile-aged Finnish women.

Adult↗

Prostate cancer risk and serologic evidence of human papilloma virus infection: a population-based case-control study.

Epidemiological evidence is accumulating that sexual history may be associated with prostate cancer, and some studies have suggested a relation between human papilloma virus (HPV) infections and prostate cancer. We measured the presence of antibodies to the major oncogenic HPV types 16, 18, and 33 among 238 subjects with untreated prostate cancer and 210 population-based control subjects. Odds ratios (ORs) were estimated from multivariate logistic regression models, controlling for age and HPV types 16, 18, and 33, simultaneously. HPV types 16 and 18 were not associated with prostate cancer [OR, 0.7; 95% confidence interval (CI), 0.4-1.3 for HPV 16; OR, 0.9; 95% CI, 0.5-1.9 for HPV 18]. There was a possible association between HPV 33 and prostate cancer (OR, 1.6; 95% CI, 1.0-2.7), and there was a significant excess risk for subjects with high antibody levels against HPV 33 (OR when the difference in absorbance exceeded 0.2, 2.3; 95% CI, 1.2-4.1). When HPV antibody levels were modeled as continuous variables, the results were qualitatively similar. The data do not support previous studies that have suggested an association with HPV 16 or 18 and prostate cancer risk. Inconsistent associations with different HPV types seen in different studies suggest that the association may be because of chance, bias, or confounding by some unknown risk factor that may associate with different HPV infections in different populations. Additional studies of the relationship between prostate cancer and other HPV types, notably HPV 33, could be helpful for clarifying the possible role of sexual risk factors.

Aged↗

Evaluation of cost-precision rations of different strategies for ELISA measurement of serum antibody levels.

Standardization and design of optimally reproducible strategies for the measurement of serum antibody levels by ELISA can present significant problems. In this article, we present a theoretical analysis of two common calculation methods in ELISA analysis (parallel line and reference line models), together with a new model, termed wPLL (a least squares-weighted modification of the parallel line model). The subject of required precision in relation to the marginal costs of increased precision has not been well explored. We compared the three different calculation methods of expressing ELISA results based on the relationship between the dose response curves obtained from the reference serum and the test samples in two viral antibody determination systems (human papillomavirus and measles). The three methods were evaluated for inter- and intraassay precision using the coefficient of variation in experiments with different numbers of dilutions and different numbers of replicates. Strategies with optimal cost-precision ratios were designed. The novel calculation method termed wPLL was preferable.

Antibodies, Viral↗

Herpes simplex virus and risk of cervical cancer: a longitudinal, nested case-control study in the nordic countries.

Human papillomaviruses (HPVs) play the major role in cervical carcinogenesis. The authors reevaluated the role of herpes simplex virus type 2 (HSV-2) in this multistage process by conducting a longitudinal, nested case-control study using 1974-1993 data and comparing the results with those from a meta-analysis of studies. A Nordic cohort of 550,000 women was followed up for an average of 5 years, after which 178 cervical carcinoma cases and 527 controls were identified. HSV-2; HPV-16, HPV-18, and HPV-33; and Chlamydia trachomatis antibodies were determined at baseline by HSV-2 glycoprotein gG-2 and HPV virus-like-particle enzyme immunoassays and by using the microimmunofluorescence method. The relative risk of cervical carcinoma was calculated by conditional logistic regression. Longitudinal studies on HSV-2 and cervical neoplasia were identified through MEDLINE (National Library of Medicine, Bethesda, Maryland), and weighted mean relative risks were calculated. Smoking (relative risk = 1.6, 95% confidence interval (CI): 1.1, 2.3) and HPV-16/HPV-18/HPV-33 (relative risk = 2.9, 95% CI: 1.9, 4.3) were both associated with cervical carcinoma. The smoking- and HPV-16/HPV-18/HPV-33-adjusted relative risks for HSV-2 were 1.0 (95% CI: 0.6, 1.7) and 0.7 (95% CI: 0.3, 1.6), respectively, for HPV seropositives. In the meta-analysis, the relative risk for HSV-2 was 0.9 (95% CI: 0.6, 1.3). In both sets of data, HSV-2 did not play a role in cervical carcinogenesis.

Adult↗

A population-based prospective study of Chlamydia trachomatis infection and cervical carcinoma.

Persistent human papillomavirus (HPV) infection is an established cause of cervical cancer, but the role of other sexually transmitted agents, most notably Chlamydia trachomatis, has not been well defined. The women participating in the population-based cervical cancer screening program in Västerbotten county of Northern Sweden were followed up for up to 26 years to identify 118 women who developed cervical cancer after having had a normal Pap smear (on average 5.6 years later; range 0.5 months-26 years). As controls, we selected another 118 women who were matched by birth cohort, time-point of sampling of the baseline normal smear and who had a normal smear at the time when the corresponding case was diagnosed with cancer. The Pap smears and cervical cancer biopsies were analyzed by PCR for C. trachomatis DNA and for HPV DNA. At baseline, C. trachomatis DNA was present in 8% of cases but not among any one of the controls. The relative risk for cervical cancer associated with past C. trachomatis infection, adjusted for concomitant HPV DNA positivity, was 17.1 (95% CI 2.6-infinity). The presence of C. trachomatis and of HPV were not interrelated. Whereas C. trachomatis was primarily found in specimens taken many years before cancer diagnosis, HPV DNA was associated with a short lag time before cancer diagnosis. Whereas most women who were HPV DNA-positive in the prediagnostic smear were also positive for the same virus in the cervical cancer biopsy, none of the women were positive for C. trachomatis in both the prediagnostic smear and in the subsequent cervical cancer. In conclusion, a prior cervical C. trachomatis infection was associated with an increased risk for development of invasive cervical cancer.

Adult↗

Risk of invasive cervical cancer associated with polymorphic HLA DR/DQ haplotypes.

The genes encoding human leukocyte antigens (HLA) have shown to be associated with cervical neoplasia. To obtain reliable data on HLA associations with cervical tumors, the study should be performed within a strictly defined cohort. To investigate the population attributable risk of cervical cancer associated with the HLA class II haplotypes DR15 and DQ6 (DQA1*0102 and DQB1*0602), we performed a nested case-control study of 85 women who developed invasive cervical cancer and 120 healthy women from a population-based cohort of Swedish women. The relative risks of cervical cancer among DR15 and DQ6-positive women were 3.73 [confidence interval (CI): 1.8-7.4] and 4.33 (CI: 2.1-8.5), corresponding to population attributable proportions of 27.9% and 30.8%, respectively. A susceptibility locus in the HLA class II region is involved in a substantial fraction of the etiology of cervical cancer.

Adult↗

Circulating enterolactone and prostate cancer risk: a Nordic nested case-control study.

Enterolactone, a phytoestrogen belonging to the class of lignans, is produced by the intestinal microflora from precursors in plant foods and has been implicated in protection against cancer. We study the effect of enterolactone on the risk of a subsequent diagnosis of prostate cancer. We conducted a longitudinal, nested case-control study by linkage of 3 biobanks to the cancer registries in Finland, Norway and Sweden, respectively. Enterolactone concentrations were measured by time-resolved fluoroimmunoassay in serum from 794 men who had a diagnosis of prostate cancer at a mean follow-up time of 14.2 years after blood collection and among 2,550 control men matched within each cohort for age (+/-2 years), date of blood collection (+/-2 months) and county. The median enterolactone concentrations did not differ between case and control subjects in the full study group (8.4 nmol/L [25th-75th percentile = 4.5-15.0] vs. 8.5 nmol/L [25th-75th percentile = 4.3-15.9]), nor in the national groups. Odds ratios of prostate cancer risk estimated by conditional logistic regression for increasing concentrations of enterolactone in quartiles in the full study group were 1.00 (referent), 1.21 (95% confidence interval [CI] = 0.96-1.52), 1.16 (95% CI = 0.91-1.47) and 1.08 (95% CI = 0.83-1.39). The OR estimate for the highest vs. the lowest quartile of enterolactone in separate analyses of the Norwegian, Finnish and Swedish cohort was 1.21 (95% CI = 0.91-1.60), 1.02 (95% CI = 0.59-1.76) and 0.87 (95% CI = 0.45-1.67), respectively. No support for the hypothesis that high circulating enterolactone is protective against prostate cancer was found.

4-Butyrolactone↗

Use of human papillomavirus DNA testing to compare equivocal cervical cytologic interpretations in the United States, Scandinavia, and the United Kingdom.

BACKGROUND: Human papillomavirus (HPV) DNA testing may be useful in clarifying equivocal cervical cytologic interpretations. One application might be to standardize the meaning of equivocal interpretations from laboratories in various regions. Because international differences may be particularly marked, international comparisons of emerging data will require clear translations of "equivocal" and similar terms. METHODS: To perform a three-country comparison, the authors selected a morphologically diverse set of 188 conventional Papanicolaou tests initially classified as "squamous atypia" from a study of more than 20,000 women in Portland, Oregon (1989-1990). Previously, five U.S. expert cytopathologists independently interpreted the slides with screening cytotechnologists' marks in place. For this comparison, one British and two Scandinavian reviewers involved in HPV research reviewed the slides after original marks had been removed. The authors compared all eight reviewers' classifications of negative, equivocal, or abnormal in a series of pairwise comparisons using the kappa statistic. They then compared cytologic interpretations with HPV DNA testing. RESULTS: Oncogenic HPV DNA detection was significantly associated with increasingly abnormal interpretations for each reader. The British reader tended to rate tests as more abnormal than the American pathologists did, whereas the Scandinavians tended to rate tests as more normal. Reference to the HPV DNA standard clarified the tendency of readers to render systematically more or less severe interpretations. For example, the Scandinavian cytologists discounted subtle (often HPV-associated) changes in favor of cytologic certainty, making HPV triage of equivocal tests less applicable there. CONCLUSIONS: International research on cytopathology, particularly on the possible uses of HPV DNA testing, will require calibration of local cytologic definitions.

Adolescent↗

Population-based type-specific prevalence of high-risk human papillomavirus infection in middle-aged Swedish women.

Human papillomavirus (HPV) DNA testing can be used to identify women at risk of the development of cervical cancer. The cost-effectiveness of HPV screening is dependent on the type-specific HPV prevalence in the general population. The present study describes the prevalence and spectrum of high-risk HPV types found in a large real-life population-based HPV screening trial undertaken entirely within the cervical screening program offered to middle-aged Swedish women. Cervical brush samples from 6,123 women aged 32-38 years were analyzed using a general HPV primer (GP5+/6+) polymerase chain reaction-enzyme immunoassay (PCR-EIA) combined with reverse dot-blot hybridization for confirmation and HPV typing by a single assay. In this study, 6.8% (95% CI 6.2-7.5) (417/6,123) were confirmed as high-risk HPV positive. Infections with 13 different high-risk HPV types were detected, of which HPV 16 was the most prevalent type (2.1%; 128/6,123), followed by HPV 31 (1.1%; 67/6,123). Any one of the HPV types 18, 33, 35, 39, 45, 51, 52, 56, 58, 59, or 66 was detected in 3.6% (223/6,123) of the women. Infection with two, three, and five types simultaneously was identified in 32, 5, and 1 women, respectively. The combination of PCR-EIA as a screening test and reverse dot-blot hybridization as a confirmatory test, was found to be readily applicable to a real-life population-based cervical screening. The type-specific HPV prevalence found support in previous modeling studies suggesting that HPV screening may be a favorable cervical screening strategy.

Adult↗

Evaluation of antibodies to human papillomavirus as prognostic markers in cervical cancer patients.

OBJECTIVES: We wished to evaluate whether the presence of antibodies to HPV or to the HPV oncoproteins E6 and E7 or type of HPV DNA is related to prognosis among cervical cancer patients. METHODS: Blood samples were drawn from 313 patients with incident, untreated cervical cancer on admission to two hospitals in Sweden. Patients were followed from enrollment in 1984-1991 until death or up to June 1999. Clinical information was obtained from a review of medical records. Survival and cause of death were ascertained from both medical records and population-based cancer registries. The correlation of survival with antibodies to HPV16, to oncoproteins E6 and E7, and to type of HPV DNA was evaluated using multivariate Cox regression analysis, including stage, age, histology, and hospital in the model. RESULTS: Stage was the only significant prognostic factor influencing cervical cancer patient survival (OR = 3.62, 95% CI = 2.71-4.83). Age over 50 was associated with increased death rate among stage I-IIa patients (OR = 2.29, 95% CI = 1.12-4.68). Presence of antibodies to the oncoproteins E6 and E7 or to the HPV16 capsid or type of HPV DNA did not associate significantly with disease prognosis. CONCLUSIONS: Antibodies to HPV16 capsids and to oncoproteins E6 and E7 or type of HPV DNA do not appear to be useful as indicators of cervical cancer prognosis.

Adenocarcinoma↗

Rate of human papillomavirus clearance after treatment of cervical intraepithelial neoplasia.

OBJECTIVE: To investigate the rate of clearance of human papillomavirus (HPV) infection after surgical treatment for cervical intraepithelial neoplasia (CIN). METHODS: One hundred nine women with CIN I-III, treated with cryosurgery or conization at a university hospital, were observed with cervical HPV deoxyribonucleic acid (DNA) testing by general primer polymerase chain reaction and HPV typing at 0, 3, 6, 9, 12, and 24 months after treatment. Penile HPV DNA was analyzed from current sexual partners. RESULTS: Eighty-one percent of evaluable women were HPV DNA positive at treatment or enrollment. One year later, seven women (9%) remained positive for the same HPV type. Most women had cleared the HPV infection diagnosed at treatment within 3 months. The cryotherapy group had lower CIN grades, was younger, and had a slower HPV clearance rate (P <.002). Only four couples had HPV DNA of the same type detected. CONCLUSION: Surgical treatment of CIN usually results in clearance of HPV infection within 3 months. Human papillomavirus DNA testing may be useful as a rapid intermediate end point for monitoring the efficacy of treatments.

Adult↗

Clustering of seropositivities for sexually transmitted infections.

BACKGROUND: Serology for different sexually transmitted infections (STIs) is useful for epidemiologic studies on the spread of STIs in different populations. Studying whether seropositivities for different STIs cluster could be useful, both for development of improved serologic markers of sexual behavior in populations and for understanding how STIs may differ in terms of the dynamics of their spread. GOAL: To evaluate the degree of clustering of different STIs in relation to sexual history. STUDY DESIGN: An age- and sexual history-stratified subsample of 275 women from a survey of healthy Swedish women seeking contraceptive advice was tested for human papillomavirus (HPV) types 6, 11, 16, 18, and 33; Chlamydia trachomatis; herpes simplex virus 2 (HSV-2); and human herpesvirus 8. RESULTS: Significant clustering was observed only for HPV types 6 and 11; for HPV types 16, 18, and 33; and for C trachomatis and HSV-2. The serologic marker that correlated best with lifetime number of sex partners was HPV type 16 (odds ratio [OR], 10.2; 95% CI, 3.8-27.6). The combined serologic marker that correlated most highly with sexual history was joint positivity for HPV types 16 and 33 (OR, 25.5; 95% CI, 5.4-120.4). CONCLUSIONS: The degree of clustering between different STIs varies from nonexistent to strong, implying that different STIs commonly have very different transmission dynamics. Certain combinations of STI serologic tests may be useful in epidemiologic studies for predicting sexual behavior in groups.

Adult↗

Serological evidence for protection by human papillomavirus (HPV) type 6 infection against HPV type 16 cervical carcinogenesis.

Human papillomavirus (HPV) exists as more than 100 genotypes. It is not well-established whether the different HPV types interfere with infection or pathogenesis by each other. Possible interactions in cervical carcinogenesis between infection with the most common HPV types (6, 11, 16, 18 and 33) were studied in a seroepidemiological case- control study of 218 women with primary untreated cervical cancer and 219 healthy age-matched control women. As previously shown, HPV-16 seropositivity was associated with cervical cancer risk [odds ratio (OR), 2.39], but HPV-16 was not associated with cervical cancer risk among HPV-6 seropositive women (OR, 1.0). The relative excess risk due to interaction between HPV-6 and -16 was -2. 35 (95% confidence interval, -0.04 to -4.65), indicating significant antagonism. The results suggest that infection with HPV-6 may interfere with HPV-16-associated cervical carcinogenesis.

Antibodies, Viral↗