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Matti Lehtinen

Publications and source records attributed to Matti Lehtinen.

30 records · Page 2Linked to original sources
PubMed2003

[Preventive vaccines against papillomavirus and cervix cancer will soon enter clinical practice].

A vaccine may protect against cancers caused by high-risk human papillomaviruses (HPVs). Sexually transmitted high-risk HPV types are almost always found in cervical cancer. Incidents of HPV type 16 and cervical cancer has more than doubled after the 1980's in Finland. HPV L1 capsid protein can be produced in the yeast, after which it assembles into virus-like-particles (VLP) and can be readily used for vaccine production. HPV VLP vaccine is well tolerated and induces ten-fold higher serum antibody levels as compared to natural infection. HPV16 VLP vaccine has shown to be 91% protective effect against HPV16 infections in the first phase III study. Neutralizing HPV antibodies, induced by HPV VLP vaccination, effectively reduce the viral load even though total elimination of the virus may not be needed. It is not known for how long the vaccine induced protection will last. Recruitment of adolescents into population-based phase III vaccination studies should be large to allow reliable cancer registry based evaluation of protective effect against grave dysplasia and cervical cancer.

Capsid Proteins↗
PubMed2003

Maternal herpesvirus infections and risk of acute lymphoblastic leukemia in the offspring.

A critical role for infection in the etiology of childhood leukemia has repeatedly been suggested. The authors undertook a case-control study nested within national maternity cohorts with altogether 7 million years of follow-up to assess the relative role of three maternal herpesvirus infections in childhood acute lymphoblastic leukemia (ALL). Offspring of 550,000 mothers in Finland and Iceland formed the joint study cohort that was followed up for cancer in the offspring before age 15 years during 1975-1997 through national cancer registries. For each index mother-case pair, three or four matched control mother-control pairs were identified from national population registers. First-trimester sera were retrieved from mothers of 342 ALL and 61 other leukemia cases and from 1,216 control mothers and were tested for antibodies to cytomegalovirus, Epstein-Barr virus (EBV), and human herpesvirus 6. Serum EBV DNA was also analyzed. Conditional logistic regression-based estimates of relative risk (odds ratio) adjusted for birth order and sibship size, and population attributable fractions, were calculated. Only EBV immunoglobulin M positivity in EBV-immunoglobulin-G-positive mothers was associated with a highly significant increased risk of ALL in the offspring (adjusted odds ratio = 2.9, 95% confidence interval: 1.5, 5.8). Results indicate that reactivation of maternal EBV infection is probably associated with childhood ALL.

Adult↗
PubMed2003

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↗
PubMed2003

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↗
PubMed2003

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↗
PubMed2003

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↗
PubMed2002

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↗
PubMed2002

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↗
PubMed2002

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↗
PubMed2002

Chlamydial heat shock protein 60--specific T cells in inflamed salpingeal tissue.

OBJECTIVE: To evaluate the role of chlamydial heat shock protein 60 (CHSP60)-specific T-lymphocytes in tubal factor infertility. DESIGN: Case series of patients with tubal factor infertility. SETTING: Infertility Clinic, Department of Obstetrics and Gynecology, Helsinki University Central Hospital and Laboratory of Cell-Mediated Immunity, National Public Health Institute, Oulu, Finland. PATIENT(S): Five patients with tubal factor infertility who underwent elective salpingectomy because of hydrosalpinges. INTERVENTION: Collection of salpingeal tissue specimens for in vitro culture of T-lymphocytes. MAIN OUTCOME MEASURE(S): Cloning of Chlamydia trachomatis and CHSP60-specific T-lymphocyte lines derived from inflamed salpingeal tissue. Cytokine production analysis of the established T-lymphocyte clones. RESULT(S): Seventy-seven (34%) of the 229 T-lymphocyte clones recognized C. trachomatis and C. pneumoniae elementary bodies as target antigens. One-third of these Chlamydia genus-specific T-lymphocyte clones further recognized CHSP60 as the target antigen. Most of the CHSP60-specific T-lymphocyte clones produced predominantly IL-10. CONCLUSION(S): CHSP60 may be an important T-lymphocyte antigen involved in the immunopathogenesis of tubal damage associated with chronic C. trachomatis infection.

Adult↗