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M Lehtinen

Publications and source records attributed to M Lehtinen.

At least 37 records · Page 2Linked to original sources
PubMed2001

Poor antibody response against human papillomavirus in adult-onset laryngeal papillomatosis.

To investigate whether adult-onset laryngeal papillomatosis induces serum antibodies to the human papillomavirus (HPV), 60 patients underwent a clinical examination, and HPV DNA from their laryngeal biopsy was assayed by PCR and HPV serology with virus-like particles as the antigen. Patients and controls (n = 53) showed no differences in their HPV 6 and 16 antibodies. Patients more often had HPV 11 antibodies, female patients more often than female controls or male patients. Of the female patients, 5 of 15 had a history of genital condylomas and, at the follow-up visit, 5 of 9 had cervical cytology consistent with genital HPV infection. The fact that HPV antibodies did not correlate with clinical features of the laryngeal disease or with HPV DNA detected in the larynx, suggests that HPV antibodies in female patients were induced by genital rather than laryngeal HPV infection. The high prevalence of abnormal Pap smears indicates that gynaecological examination of female adult-onset laryngeal papilloma patients is warranted.

Age of Onset↗
PubMed2001

Efficacy of preventive human papillomavirus vaccination.

Interplay between host immune system and expression of human papillomavirus (HPV) early (E) and late (L) genes during infection has a central role in the surveillance of virus-induced neoplastic cervical lesions. Recently, new features of this interplay have been discovered. However, not enough is yet known of the relative roles of different E and L proteins, human lymphocyte antigens (HLAs) and specific co-factors in the natural history of these lesions in order to guarantee efficacy of preventive HPV vaccination. The ultimate knowledge can only be provided by phase III/IV vaccination trials which are starting in the near future. The present review attempts to answer one fundamental question: which of the vaccine candidates is likely to be most successful.

Animals↗
PubMed2000

Chlamydia trachomatis infection as a risk factor for invasive cervical cancer.

Cervical carcinoma is a sexually transmitted disease most strongly linked with human-papillomavirus (HPV) infection. We conducted a prospective sero-epidemiologic study to evaluate the role of Chlamydia trachomatis infection in the development of cervical carcinoma, with invasive cancer as an end point. A nested case-control study within a cohort of 530000 Nordic women was performed. Linking data files of 3 Nordic serum banks and the cancer registries of Finland, Norway and Sweden identified 182 women with invasive cervical carcinoma diagnosed during a mean follow-up of 5 years after serum sampling. The serum samples of the cases and matched cancer-free controls were analyzed for IgG antibodies to C. trachomatis, C. pneumoniae (a control microbe) and HPV types 16, 18 and 33, as well as for serum cotinine (an indicator of tobacco smoking). Serum antibodies to C. trachomatis were associated with an increased risk for cervical squamous-cell carcinoma (HPV- and smoking-adjusted OR, 2.2; 95% CI, 1.3-3.5). The association remained also after adjustment for smoking both in HPV16-seronegative and -seropositive cases (OR, 3.0; 95% CI, 1.8-5.1; OR, 2.3, 95% CI, 0. 8-7.0 respectively). No such association was found for C. pneumoniae. Our prospective study provides sero-epidemiologic evidence that infection with C. trachomatis confers an increased risk for subsequent development of invasive squamous-cell carcinoma of the uterine cervix.

Adenocarcinoma↗
PubMed2000

Prerequisites for human papillomavirus vaccine trial: results of feasibility studies.

BACKGROUND AND AIMS: Oncogenic human papillomaviruses (HPVs) are the major cause of cervical cancer and associated cancers. First generation preventive vaccines against HPVs are entering clinical trials. Therefore, it is time to consider prerequisites of field trials in Finland. RESULTS: Incidence of cervical cancer is increasing in young women which is not unexpected since risk taking behavior among young women has also increased. In the developed countries up to 44% of cervical cancer cases are attributable to HPV16 infection alone. However, high risk HPV types other than HPV16 and HPV18 are emerging in the population based on HPV DNA pilot screening studies. Annual attack rates among young women less than 25 years of age is 2.3% for HPV16 infection, and 0.03% for CIN3 invasive cervic cancer. Thus, sample size estimates for HPV vaccine efficacy trial are approximately 1000 when the endpoint is HPV16 infection, and approximately 15000 when the endpoint is >/=CIN3 or worse assuming that the vaccine efficacy is 70%. Both HPV vaccine trial acceptability and compliance rates at routine visits of the general Finnish female population are going to be high based on a pilot study. CONCLUSION: Prerequisites for large scale field trials on HPV vaccination are fulfilled in Finland.

Adult↗
PubMed2000

Prospects for phase III-IV HPV vaccination trials in the Nordic countries and in Estonia.

BACKGROUND: oncogenic, i.e. high risk human papillomavirus (hrHPV) types are the major cause of invasive cervical cancer (ICC). Putatively licensable vaccines against the hrHPVs have been developed and are approaching clinical phase III trials that use persistent HPV infection as end point. Direct extension of the phase III trials towards long-term end points (ICC and its immediate precursors: carcinoma in situ and severe dysplasia, i.e. cervical intraepithelial neoplasia grade III, CINIII) is important, to avoid early contamination of the target population by opportunistic use of licensed HPV vaccines. Country-wide registration on population and health events in a stable population of 25 million make Estonia and the Nordic countries a unique venue for long-term evaluation of cervical cancer control measures. Mass-screening programmes exist in all Nordic countries, but not in Estonia. AIM: design of phase III-IV trials for evaluation of protection against ICC and CINIII by preventive HPV vaccines based on cancer registry follow-up. RESULTS: in the Nordic countries, population based randomisation of all 15-year-old women to the vaccination (vaccine and placebo) and reference cohorts entering conventional Pap-smear screening after a clinical phase III trial would assure comparability of the cohorts. Enrollment of 10094 vaccinees +10094 placebo vaccinees +30282 other hrHPV negative women without vaccination at the age of 16 would give 80% power for the demonstration of 70% vaccine efficacy (VE) against ICC in 20 years by cancer registry follow-up. On the other hand, vaccination of 8303 Estonian hrHPV negative women among the entire 15-year-old female birth cohort (about 10000 women) with an already licensed HPV vaccine would enable demonstration of 70% VE against ICC by 20 years of registry follow-up of these and comparable 16606 women identified among the 16-19-year-old birth cohorts. CONCLUSIONS: evaluation of the protective effect of an HPV vaccine against ICC is possible both in countries with or without mass-screening. The effects of vaccination on spread of different HPVs in the population would need to be monitored, especially in Estonia. Ethical aspects, cost-benefit evaluation and comparisons with other new means of cervical cancer control warrant further investigation.

Adolescent↗
PubMed2000

Joint effect of HPV16 with Chlamydia trachomatis and smoking on risk of cervical cancer: antagonism or misclassification (Nordic countries).

OBJECTIVES: To estimate the joint effects of infections with human papillomavirus type 16 (HPV16) and Chlamydia trachomatis and smoking on the risk of cervical cancer. To study whether the joint effects can be accounted for by misclassification in the HPV serology. METHODS: A nested case-control study with incidence density sampling was conducted in three cohorts of 530,000 women, who donated serum samples to three Nordic serum banks in 1973-1994. The main outcome measure is the odds ratio (OR) of incidence rates of invasive cervical squamous cell carcinoma (SCC) among those seropositive for HPV16 and/or C. trachomatis and/or with increased levels of cotinine in serum compared to those negative for all the three exposures. RESULTS: Two hundred eight women with SCC and 624 matched controls were identified during a mean follow-up of 5 years through linkage to the national cancer registries. Exposure to past infections and smoking was defined by presence of specific IgG antibodies to HPV16 and C. trachomatis and increased levels of serum cotinine. Observed ORs were compared to OR = 20 for HPV16 and accounting the differences for by misclassification bias. OR = 20 was elected as a gold standard on the basis of other studies with PCR-based analyses and a follow-up design. Each of the three exposures was associated with an increased risk of SCC (OR = 5.4 for HPV16, 3.4 for C. trachomatis and 1.8 for cotinine). The interaction was antagonistic (observed OR = 2.5 among those positive for all three exposures as compared to OR = 33 expected on the basis of multiplicative single effects (p = 0.047)). The antagonism could not totally be accounted for by any credible combination of sensitivity and specificity of HPV16 serology. CONCLUSION: HPV16, C. trachomatis, and smoking are likely to be risk factors of SCC with strong antagonistic joint effect. Non-differential misclassification in serology for HPV16 could be ruled out (but only some types of differential) as an alternative explanation for the observed antagonism.

Antibiosis↗
PubMed2000

Type specificity and significance of different isotypes of serum antibodies to human papillomavirus capsids.

Isotype-specific serum antibody responses against human papillomavirus (HPV) type 16 were evaluated by use of cross-sectional, prospective, and population-based seroepidemiologic studies. IgG1 and IgA were the most abundant isotypes. No sample contained IgG2, and <25 samples contained IgG3 or IgM. Total IgG, IgA, and IgG1 were HPV type specific and were associated with HPV-16 DNA (odds ratios [ORs], 5.4, 5.0, and 5.9, respectively; P<.001) but not with other HPV DNA (ORs, 1.2, 1.2, and 0.8, respectively; P value was not significant). Total IgG and IgG1 were strongly associated with number of lifetime sex partners (P<.001); IgA was only associated with number of recent sex partners and lifetime sex partners among younger women. Total IgG, IgG1, and IgA were associated with cervical intraepithelial neoplasia type III and also predicted risk of future cervical neoplasia. IgG and IgG1 appeared to mark lifetime cumulative exposure, whereas IgA may mark recent or ongoing infection.

Adolescent↗
PubMed2000

Chlamydia trachomatis reactive T lymphocytes from upper genital tract tissue specimens.

Chlamydia trachomatis infection is associated with pelvic inflammatory disease (PID) and tubal factor infertility (TFI). We investigated the role of C. trachomatis as a target antigen of endometrial and salpingeal tissue lymphocytes derived from PID and TFI patients. Antigen specificity of the tissue originated T lymphocyte lines (TLL) was tested against C. trachomatis elementary bodies and chlamydial heat shock protein 60 (CHSP60). C. trachomatis antigen stimulated proliferation in two out of eight endometrial TLL derived from PID patients and three out of four TLL derived from TFI patients. All (n = 4) TLL derived from the salpingeal specimens responded to CHSP60 compared with only one out of 12 TLL derived from the endometrial specimens. In-vivo expression of interferon-gamma (IFN-gamma) mRNA revealed that it was present in nine of 13 specimens obtained from PID patients. The dominant activity of type-1 T lymphocytes was confirmed by the in-vitro production of IFN-gamma (median 1007 pg/ml) from all (n = 5) C. trachomatis specific TLL while IL-5 secretion was lower (median 779 pg/ml). In conclusion, C. trachomatis reactive TLL were established from in-vivo activated lymphocytes from the upper genital tract tissue of PID and TFI patients. The reactivity of the salpingeal TLL to CHSP60 provided further evidence that immunoreactivity to CHSP60 is a predominant response in patients with tubal damage.

Adolescent↗
PubMed2000

Seropositivity to multiple sexually transmitted infections is not common.

BACKGROUND: Seropositivity for several sexually transmitted infections (STIs) is often used as a surrogate measure of sexual behavior. The authors assessed the concomitant seropositivity for STIs in women. GOAL: To estimate the excess of concomitant seropositivity for four STIs among fertile-aged women assuming no coinfections above what would be expected at random. STUDY DESIGN: Antibodies to herpes simplex virus type 2, human papillomavirus type 16, HIV, Chlamydia trachomatis, and Treponema pallidum were determined from a random sample of 1110 pregnant women in Tallinn, Estonia. RESULTS: A total of 310 combinations of the concomitant seropositivity were observed, whereas only 193 were expected by chance. Among persons seropositive for two STIs, 78 extra combinations were observed, whereas for three STIs, 35 extra combinations were observed. For four STIs, 3.8 extra combinations were found. CONCLUSIONS: Seropositivity to multiple STIs is not common. This fits the concept of different transmission probabilities and the spread of the STIs, and suggests that seropositivity alone should be used with caution as a surrogate to sexual behavior in women.

Adolescent↗
PubMed2000

Attack rates of human papillomavirus type 16 and cervical neoplasia in primiparous women and field trial designs for HPV16 vaccination.

BACKGROUND: Identification of human papillomavirus type 16 (HPV16) as the major risk factor for cervical neoplasia, and mass production of DNA free HPV capsids have paved the way to preventive vaccination trials. Design of such trials requires reliable attack rate data. OBJECTIVE: Determination of (1) HPV16 and (2) cervical neoplasia attack rates in primiparous women. Estimation of actuarial sample sizes for HPV16 vaccination phase IV trials. DESIGN: A longitudinal cohort study. METHODS: Population based Finnish Maternity Cohort (FMC) and Finnish Cancer Registry (FCR) were linked for the identification of two cohorts of primiparous women: (1) a random subsample of the FMC: 1656 women with two pregnancies between 1983-9 or 1990-6 and living in the Helsinki metropolitan area, and (2) all 72,791 primiparous women living in the same area during 1983-94. Attack rate for persistent HPV16 infection (1) was estimated in 1279 seronegative women by proportion of seroconversions between the first and the second pregnancy. Comparable 10 year cumulative incidence rate (CR) of cervical intraepithelial neoplasia grade III and cervical cancer (CIN III+) (2) was estimated based on cases registered at the FCR during 1991-4. RESULTS: The HPV16 attack rates were 13.8% (< 18 years), 7.0% (18-19 years), 2.3% (21 years), 2.4% (23 years), and 4.5% (< 25 years). Number of vaccinees required for a 5 year efficacy trial with persistent HPV16 infection as the end point ranged between 1000 and 3900, assuming 80% power, 90%-70% vaccine efficacy (VE), and misclassification. The CRs of CIN III+ were 0.33% (< 18 years), 0.44% (18-19 years), 0.21% (20-24 years), and 0.28% (< 25 years). Number of vaccinees required for a 10 year efficacy trial with HPV16 positive CIN III+ as the end point was 15,000 assuming 80% power, 90% VE, and 75% aetiological fraction of CIN III+ for HPV16. CONCLUSIONS: The attack rates of HPV16 and CIN III+ identify primiparous women under 25 years of age among target populations for postnatal HPV vaccination at phase II/III trials.

Adolescent↗
PubMed2000

Detection of Chlamydia pneumoniae-reactive T lymphocytes in human atherosclerotic plaques of carotid artery.

Linkage between Chlamydia pneumoniae infection and atherosclerosis has been confirmed in several studies, but the precise role of this organism in the disease process is not known. We investigated the relation and reactivity of T lymphocytes of human carotid plaques to C pneumoniae antigens. Tissue specimens were obtained from 17 patients who underwent carotid endarterectomy. Immunohistological staining and/or in situ hybridization revealed the presence of C pneumoniae in 11 (64%) of the 17 of the cases. Inflammatory infiltration seen in the vessel walls consisted primarily of CD45RO+ T-memory lymphocytes (median 80%, range 50% to 90%), whereas CD20+ B cells and monocytes were in minor proportion. In vivo activated T lymphocytes were propagated from the specimens with interleukin-2, and the antigen specificity of the established T-cell lines (TLLs) was analyzed against C pneumoniae elementary body antigen. TLLs were established from all 17 carotid tissues but none from the control specimens of ascending aorta. C pneumoniae was recognized as a specific T-cell-stimulating antigen in 7 (41%) of 17 cases. Further analyses of the C pneumoniae-reactive TLLs showed that chlamydial 60-kDa heat-shock protein induced specific proliferation in 5 (71%) of 7 cases and revealed 2 haplotype (DRB1*1502 and DQB1*06) binding motifs in human 60-kDa heat-shock protein. C pneumoniae was identified as a specific microbial antigen recognized by 41% of TLLs propagated from in vivo activated plaque T cells. Our results suggests that cell-mediated immunity to C pneumoniae plays a role in the atherosclerotic process and that this response may involve autoimmunity.

Aged↗
PubMed1999

No excess risk of cervical carcinoma among women seropositive for both HPV16 and HPV6/11.

Human papillomavirus (HPV) types 16 and 18 are the major risk factors for cervical carcinoma, whereas HPV types 6 and 11 cause benign genital lesions. We wanted to study the joint effect of simultaneous infections with the oncogenic and non-oncogenic HPV types on risk of subsequent development of cervical carcinoma. A cohort of 530,000 women who had donated blood samples to Nordic serum banks between 1973 and 1994 was followed up by linkage to national cancer registries. We identified 182 prospective cases with invasive cervical carcinoma and selected 538 matched controls at random. HPV 6, 11, 16, 18 and 33 seropositivity was used as a marker for the different HPV infections, and seropositivity for Chlamydia trachomatis and cotinine were used as markers for risk-taking sexual behavior and smoking respectively. The adjusted odds ratio (OR) of cervical squamous-cell carcinoma (SCC) was 2.2 for HPV6/11 among HPV16 seronegatives and 5.5 for HPV16 among HPV6/11 seronegatives. Assuming multiplicative joint effect, the expected OR for seropositivity to both HPV6/11 and HPV16 would have been 12, but the observed OR was 1.0. The antagonistic interaction was statistically significant (p = 0.001) and present also under deterministic considerations of possible misclassification bias. Antagonistic interactions were also detected for combinations of HPV16 and HPV18 and of HPV16 and HPV33. The results are in line with the concept that HPV-specific immunity protects against SCC and support primary prevention of SCC by vaccination against the HPVs.

Adult↗
PubMed1999

Interactions between human papillomavirus and other sexually transmitted agents in the etiology of cervical cancer.

The interplay between human papillomavirus, notably type 16, and HIV in cervical carcinogenesis leads to persistent infection and cervical neoplasia by destruction of the afferent arm (Langerhans cells) of the host immune system. The joint effect takes place at the early stages of squamous intraepithelial lesions and has severe consequences if left untreated. The recent increase of cervical cancer mortality in young women in developed countries may well be a result of the HIV epidemic. Infection with Chlamydia trachomatis is associated with cervical squamous cell carcinoma but not with cervical adenocarcinoma, and the association remains after adjusting for human papillomavirus 16. Joint effects of C. trachomatis and the human papillomaviruses have not been studied at the population level but indirect evidence from epidemiological studies suggests that the interaction might be different (synergistic versus antagonistic) at different stages (cervical intraepithelial neoplasia versus invasive cervical cancer) of cervical carcino-genesis. Concomitant exposure to human papillomaviruses 6 or 11 and human papillomavirus type 16 has not been shown to result in excess risk of cervical squamous cell carcinoma. This antagonistic joint effect was also discovered between human papillomavirus types 18 and 16, as well as 33 and 16. Herpes simplex virus type 2 antibodies are associated with a modest risk of cervical cancer, which is not surprising since the presence of herpes simplex virus antibodies reflects risk-taking sexual behaviour. However, no excess risk remains after adjustment for human papillomavirus type 16, and no interaction between these two viruses has been found in epidemiological studies. Evidence of interaction between human papillomavirus type 16 and the other members of the herpesvirus family is still at an experimental level and difficult to judge. Little progress has been made in the most promising experimental association between the oncogenic human papillomaviruses and adeno-associated viruses. In addition to the well established interaction between human papillomaviruses and HIV, intriguing interactions are emerging between the human papillomaviruses and C. trachomatis, as well as between the different human papillomavirus types.

Journal Article↗
PubMed1999

Serological evaluation of herpes simplex virus type 1 and type 2 infections in pregnancy.

OBJECTIVE: Serological evaluation of herpes simplex virus infections during pregnancy. METHODS: 2991 serum samples were obtained during 1st, 2nd, and 3rd trimester from 997 pregnant women. Baculovirus expressed glycoproteins gG1 (HSV-1) and gG2 (HSV-2) were used as antigens in ELISA for HSV-1 and HSV-2 IgG and IgA antibodies. RESULTS: The prevalence of HSV-1 gG1 antibodies was 70% and that of HSV-2 gG2 antibodies 16%. Among susceptible women we found five (0.6%) cases with serological evidence of primary HSV-2 infection during pregnancy. Evidence of active HSV-1 infection was found in nine (0.9%) cases. Decline of HSV-2 gG2 IgG antibody levels during pregnancy was pronounced compared with HSV-1 gG1 IgG antibody levels (p < 0.01); also the proportion of seroreversions was considerably higher among HSV-2 seropositives (25%) than among HSV-1 seropositives (3%) (p < 0.001). CONCLUSIONS: HSV-2 gG2 IgG antibodies were readily distinguished from HSV-1 gG1 IgG antibodies by the glycoprotein gG ELISAs. Serological assays for gG2 antibodies should guard against the decline of specific antibodies during pregnancy.

Adult↗
PubMed1999

Low levels of serum vitamins A and E in blood and subsequent risk for cervical cancer: interaction with HPV seropositivity.

Nutritional factors have been associated with risk of cervical cancer, but it is unclear whether the associations are of etiological significance or secondary to human papillomavirus (HPV) exposure. A delineation of this question requires a prospective study with invasive cancer as the end point. We conducted a nested case-control study in Finland and Sweden within a joint cohort of 405,000 women followed up for, on average, 4 years. Blood samples from 38 prospective cases of invasive cervical cancer diagnosed between 1985 and 1994 and 116 controls matched for age, country, and sample storage time were available for the study. Levels of retinol or unoxidized alpha-tocopherol in the blood were not risk factors for cervical cancer. However, joint-effect analysis of low levels of retinol disclosed statistically significant (p = 0.023) synergistic (more than multiplicative) interaction with HPV (HPV16, HPV18, or HPV33) seropositivity (observed relative risk = 2.6, 95% confidence interval = 0.7-8.8, expected relative risk = 0.3). Retinol might act as an effect modifier of the HPV-associated risk for cervical cancer; exposed women may require adequate levels for immunologic surveillance of HPV.

Adult↗
PubMed1998

Sero-epidemiological association between human-papillomavirus infection and risk of prostate cancer.

Some epidemiological studies of prostate cancer have suggested the existence of a sexually transmitted risk factor, and some studies have reported the presence of human papillomavirus (HPV) DNA in prostate-cancer tissue. To perform a sero-epidemiological evaluation of whether HPV infection is associated with increased risk for prostate cancer, we performed a nested case-control study within a serum bank containing samples from 20,243 healthy Finnish men. We identified 165 cases of prostate cancer that were diagnosed up to 24 years after donation of the serum sample. Two control subjects per case were selected, matched for gender, age and municipality of residence. Serum samples were analyzed for the presence of IgG antibodies against 4 HPV types and against Chlamydia. The presence of antibodies against HPV type 18 was associated with a 2.6-fold increased risk of developing prostate cancer during follow-up (p < 0.005). HPV type 16 tended to be associated with subsequent prostate-cancer occurrence (relative risk: 2.4, p = 0.06), whereas seropositivity for HPV type 11 or type 33 or for Chlamydia was not associated with risk. The results suggest that infection with oncogenic HPV might be involved in the etiology of a minority of prostate cancers.

Adult↗
PubMed1998

Comparison between four and eight cycles of intensive chemotherapy in adult acute myeloid leukemia: a randomized trial of the Finnish Leukemia Group.

In acute myelogenous leukemia (AML) intensive postremission treatment is needed for an optimal result. However, it is not known how long the treatment should last and how many courses are necessary. The object of this prospective study was to compare four and eight intensive chemotherapy cycles in the treatment of adult de novo AML. In a multicenter study, 248 consecutive patients, aged from 16 to 65 years, were treated with intensive induction treatment. The patients in remission after two courses were randomized to receive either two (short arm) or six (long arm) additional intensive cycles of chemotherapy. The median follow-up time of the living patients is 68 months. Of the patients, 77% achieved complete remission, and 36% of all patients survived for 5 years. Seventy-three patients were randomized to the short arm and 66 to the long arm. There was no significant difference in the relapse-free survival (median 21 months vs 17 months) or overall survival (43 months vs 39 months) between the short and long arms, respectively. Treatment-related deaths occurred in 31 patients (13%), 11 of them in first remission. More than one-third of the patients survived for 5 years. It seems probable that the first few months after diagnosis are decisive for the prognosis if the chemotherapy is intensive, and further treatment cannot markedly influence the outcome.

Aclarubicin↗