Matti Lehtinen

University of Tampere, Tammerfors, Pirkanmaa, Finland

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Publications (281)1322.92 Total impact

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    ABSTRACT: We report final event-driven analysis data on the immunogenicity and efficacy of the human papillomavirus (HPV)-16/18 AS04-adjuvanted vaccine in young women aged 15-25 years from the PApilloma TRIal against Cancer In young Adults (PATRICIA; NCT001226810). The total vaccinated cohort (TVC) included all randomised participants who received at least one vaccine dose (vaccine, n=9319; control, n=9325) at months 0, 1 and/or 6. The TVC-naïve (vaccine, n=5822; control, n=5819) had no evidence of high-risk HPV infection at baseline approximating adolescent girls targeted by most HPV vaccination programmes. Mean follow-up was approximately 39 months after the first vaccine dose in each cohort. At baseline, 26% of women in the TVC had evidence of past and/or current HPV-16/18 infection. HPV-16 and HPV-18 antibody titres post-vaccination tended to be higher among 15-17 year-olds than 18-25 year-olds. In the TVC, vaccine efficacy (VE) against cervical intraepithelial neoplasia grade 1 or greater (CIN1+), CIN2+ and CIN3+ associated with HPV-16/18 was 55.5% (96.1% CI: 43.2, 65.3), 52.8% (37.5, 64.7) and 33.6% (-1.1, 56.9). VE against CIN1+, CIN2+ and CIN3+ irrespective of HPV DNA was 21.7% (10.7, 31.4), 30.4% (16.4, 42.1) and 33.4% (9.1, 51.5) and consistently significant only in 15-17 year-old women (27.4% [10.8, 40.9], 41.8% [22.3, 56.7] and 55.8% [19.2, 76.9]). In the TVC-naïve, VE against CIN1+, CIN2+ and CIN3+ associated with HPV-16/18 was 96.5% (89.0, 99.4), 98.4% (90.4, 100) and 100% (64.7, 100); and irrespective of HPV DNA was 50.1% (35.9, 61.4), 70.2% (54.7, 80.9) and 87.0% (54.9, 97.7). VE against 12-month persistent infection with HPV-16/18 was 89.9% (84.0, 94.0) and against HPV-31/33/45/51 was 49.0% (34.7, 60.3). In conclusion, vaccinating adolescents before sexual debut has a substantial impact on the overall incidence of high-grade cervical abnormalities, and catch-up vaccination up to 18 years of age is most likely effective.
    Clinical and vaccine Immunology: CVI 02/2015; DOI:10.1128/CVI.00591-14 · 2.37 Impact Factor
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    ABSTRACT: High-risk human papillomaviruses (hrHPV) cause anogenital and oropharyngeal cancers. HPV-16/18 virus-like particle vaccine formulated with an AS04 adjuvant is very efficacious against hrHPV associated precancers but the herd effects of different vaccination scenarios are not known. Our cluster randomized trial (NCT00534638) assesses the overall and herd effects of vaccinating girls vs. girls and boys. In two school-years (2007-2008 and 2008-2009) we invited 80,272 1992-1995 born early adolescents to a CRT in 33 communities a priori stratified by low, intermediate and high HPV-16/18 seroprevalence. In 11 Arm A communities 90% of participating girls and boys were assigned to receive HPV-16/18 vaccine, in 11 Arm B communities 90% of girls were assigned to receive HPV-16/18 vaccine - boys were assigned to receive hepatitis B-virus (HBV) vaccine, and in 11 Arm C communities all were assigned to receive HBV-vaccine. Prevalence of HPV in vaccinated and unvaccinated girls is studied at age 18.5 years. Recruitment resulted in equal enrolment of four birth cohorts (born 1992-1995) comprising altogether 32,176 (40% response) early adolescents: 20,515 girls (50.5-53.0% response by arm) and 11,661 boys (21.9-31.6%% response by arm). At the age of 15 years, 79.3% of the vaccinees completed a questionnaire. Among them >98% were living at, and during the week-ends 1.3-1.6% stayed outside, the study site communities. Smoking habit and alcohol consumption were similar in the different trial arms, also mean-age of menarche (12.4 years) and 1st ejaculation (12.6 years), and sexual behaviour (among those <25%, who had had sexual debut) did not differ by arm: mean-age at the sexual debut 14.3 and 14.4 in girls and boys, and proportions of those with multiple (≥5) life-time sexual partners (6.5-7.5%) at the age of 15 years. Uniform residential, life-style and sexual behaviour characteristics indicate successful randomization/enrolment of the CRT. Our CRT will verify modelled predictions on up to 31% herd effect of vaccinating both girls and boys with moderate vaccine coverage - quantifying overall effectiveness of different strategies it will soon guide how to implement HPV vaccination. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.
    Vaccine 01/2015; 33(10). DOI:10.1016/j.vaccine.2014.12.019 · 3.49 Impact Factor
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    ABSTRACT: Insulin-like growth factor-I (IGF-I) signaling may promote ovarian tumor development by exerting mitotic, anti-apoptotic, and pro-angiogenic effects. During pregnancy, maternal production of IGF-I is regulated by placental growth hormone (GH). Parity is an established protective factor for ovarian cancer, however, no prior study has evaluated placental GH and IGF-I in pregnancy and epithelial ovarian cancer (EOC). Prior prospective studies on the association between IGF-I and EOC in non-pregnant populations were inconclusive and did not address associations in subtypes of EOC. Among members of the Finnish Maternity Cohort and the Northern Sweden Maternity Cohort we identified 1,045 EOC cases, diagnosed after recruitment (1975-2008) and before March 2011, and 2,658 individually matched controls. Placental GH and IGF-I were measured in serum from the last pregnancy before EOC diagnosis or selection as control. We used conditional logistic regression to estimate odds ratios (OR) and 95% confidence intervals [CI] for tertiles and a doubling of hormone concentrations. Higher IGF-I was associated with a non-significant decrease in risk for invasive (ORT3 vs. T1: 0.79 [0.62-1.02]; ptrend=0.07) and endometrioid tumors (ORT3 vs. T1: 0.55 [0.28-1.07]; ptrend=0.07). The protective association between higher IGF-I levels and risk of invasive EOC was stronger in analyses limited to women aged <55 years at diagnosis (ORT3 vs. T1: 0.74 [0.57-0.96]; ptrend=0.03). Our study provides the first data on placental GH and IGF-I in pregnancy and EOC risk overall and by subtype. Our data suggest higher IGF-I levels in pregnancy may be associated with lower risk of invasive and endometrioid EOC. This article is protected by copyright. All rights reserved.
    International Journal of Cancer 12/2014; DOI:10.1002/ijc.29387 · 5.01 Impact Factor
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    ABSTRACT: Well-established associations between reproductive characteristics and epithelial ovarian cancer (EOC) support an involvement of sex steroid hormones in the etiology of EOC. Limited previous studies have evaluated circulating androgens and the risk of EOC, and estrogens and progesterone have been investigated in only one of the previous studies. Furthermore, there is little data on potential heterogeneity in the association between circulating hormones and EOC by histological subgroup. Therefore, we conducted a nested case-control study within the Finnish Maternity Cohort and the Northern Sweden Maternity Cohort to investigate the associations between circulating pre-diagnostic sex steroid concentrations and the histological subtypes of EOC. We identified 1052 EOC cases among cohort members diagnosed after recruitment (1975-2008) and before March 2011. Up to three controls were individually matched to each case (n=2694). Testosterone, androstenedione, 17-hydroxyprogesterone (17-OHP), progesterone, estradiol (E2), and sex hormone-binding globulin levels were measured in serum samples collected during the last pregnancy before EOC diagnosis. We used conditional logistic regression to estimate odds ratios (ORs) and 95% CIs. Associations between hormones and EOC differed with respect to tumor histology and invasiveness. Sex steroid concentrations were not associated with invasive serous tumors; however, doubling of testosterone and 17-OHP concentration was associated with approximately 40% increased risk of borderline serous tumors. A doubling of androgen concentrations was associated with a 50% increased risk of mucinous tumors. The risk of endometrioid tumors increased with higher E2 concentrations (OR: 1.89 (1.20-2.98)). This large prospective study in pregnant women supports a role of sex steroid hormones in the etiology of EOC arising in the ovaries.
    Endocrine Related Cancer 12/2014; 21(6):831-44. DOI:10.1530/ERC-14-0282 · 4.91 Impact Factor
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    ABSTRACT: Pregnancy, parity and circulating steroid hormone levels are associated with risk of breast cancer, but little is known about hormone concentrations during pregnancy and subsequent breast cancer risk. We evaluated early pregnancy (<140 days gestation) serum estradiol, estrone, progesterone, and testosterone and breast cancer risk in a nested case-control study in the Finnish Maternity Cohort. The cohort includes 98% of pregnancies registered in Finland since 1983. Individuals with samples collected in the first pregnancy leading to a live birth were eligible. Breast cancer cases (n=1,199) were identified through linkage with the Finnish Cancer Registry; 2,281 matched controls were selected using incidence density sampling. Odds ratios were calculated using conditional logistic regression. Hormone concentrations were not associated with breast cancer overall. Estradiol was positively associated with risk of breast cancer diagnosed age <40 (4th vs. 1st quartile OR 1.60 (1.07-2.39); ptrend=0.01), and inversely associated with breast cancer diagnosed at age ≥40 (4th vs. 1st quartile OR 0.71 (0.51-1.00); ptrend=0.02). Elevated concentrations of the steroid hormones were associated with increased risk of estrogen receptor (ER) and progesterone receptor (PR) negative tumors in women age <40 at diagnosis. We observed no association between steroid hormones and ER+/PR+ disease. These data suggest a positive association between high concentrations of early pregnancy steroid hormones and risk of ER-/PR- breast cancer in women diagnosed age <40, and an inverse association for overall breast cancer diagnosed age ≥40. Further research on pregnancy hormones and risk of steroid receptor negative cancers is needed to further characterize this association.
    Cancer Research 10/2014; 74(23). DOI:10.1158/0008-5472.CAN-14-2150 · 9.28 Impact Factor
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    ABSTRACT: Background The AS04-adjuvanted bivalent L1 virus-like-particle (VLP) vaccine (Cervarix™) against infection with human papillomavirus (HPV) types 16/18 holds great promise to prevent HPV16/18 infections and associated neoplasias, but it is important to rule out significant co-factors of the neoplasias like smoking. Methods We conducted a pilot study to compare the quantity and quality of HPV16/18 antibody response at baseline and 7 months post vaccination in 104 non-smoking and 112 smoking female participants vaccinated at 0, 1 and 6 months with Cervarix™ (55 and 48 study participants) or with Hepatitis A vaccine (HAVRIX™) (48 and 64 participants, respectively). These 216 women were a sub-sample of 4808 baseline 16- to 17-year old Finnish women initially enrolled in the double-blind, randomized controlled phase III PATRICIA trial. Following end-of-study unblinding in 2009 they were randomly chosen out of all the participants of the three major Finnish PATRICIA study sites in the Helsinki metropolitan area (University of Helsinki, N = 535, and Family Federation Finland, N = 432) and Tampere (University of Tampere, N = 428). Following enrolment, serum samples were collected at month 0 and month 7 post 1st vaccination shot, and were analysed for levels and avidity of IgG antibodies to HPV16 and HPV18 using standard and modified (4 M urea elution) VLP ELISAs. Results We found that at month 7 post vaccination women who smoked (cotinine level > 20 ng/ml) had levels of anti-HPV16/18 antibodies comparable to those of non-smoking women. Low-avidity HPV16/18 IgG antibodies were observed in 16% of the vaccinated women, and active smoking conferred a three-fold increased risk (95% CI 1.0-9.3) of having the low-avidity antibodies. Conclusion Our data suggest that while smoking does not interfere with the quantity of vaccine-induced peak IgG levels, it may affect the avidity of IgG induced by HPV16/18 vaccination.
    BMC Research Notes 07/2014; 7(1):445. DOI:10.1186/1756-0500-7-445
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    ABSTRACT: We evaluated the overall coverage, frequency and costs of Pap testing by screening modality and health care provider in Finland. Information about Pap testing in the Finnish female population of 2.7 million was obtained from nationwide population-based registry data. Among women aged 25-69 years, 87% had had a Pap test taken within or outside the organised programme at least once during the last 5 years and half of those screened in the organised programme had also had at least one Pap test taken outside the programme. Of the annual average of 530,000 Pap tests taken, 84% were taken for screening purposes and 16% as follow-up. Forty percent of the 446,000 annual screening tests were taken in the organised programme, 55% as opportunistic tests in public primary or student health care or by private providers and 5% in public secondary health care. One-fifth of all opportunistic screening Pap tests were taken from women aged <25. The voluminous opportunistic Pap testing in public primary health care was concentrated in young women aged 25-29 whereas the bulk of opportunistic testing in private health occurred in age groups eligible for organised screening. The total cost of all screening Pap tests was €22.4 million, of which 71% incurred in opportunistic screening. Of the 84,000 annual follow-up Pap tests and their €8.3 million total costs, ∼60% incurred in organised screening or in secondary health care.
    International Journal of Cancer 07/2014; 135(1). DOI:10.1002/ijc.28646 · 5.01 Impact Factor
  • Women s Health 07/2014; 10(4):341-3. DOI:10.2217/whe.14.35
  • Clinical Cancer Research 05/2014; 19(19_Supplement):B2-B2. DOI:10.1158/1078-0432.OVCA13-B2 · 8.19 Impact Factor
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    ABSTRACT: Background. We examined risk of newly detected HPV infection and cervical abnormalities in relation to HPV-16/18 antibody levels at enrollment in PATRICIA (PApilloma TRIal against Cancer In young Adults; NCT00122681).Methods. Using Poisson regression, we compared risk of newly detected infection and cervical abnormalities associated with HPV-16/18 between seronegative versus seropositive women (15-25 years) in the control arm (DNA-negative at baseline for the corresponding HPV type [HPV-16: n=8193; HPV-18: n=8463]).Results. High titers of naturally-acquired HPV-16 antibodies and/or linear trend for increasing antibody levels were significantly associated with lower risk of incident and persistent infection, atypical squamous cells of undetermined significance or greater (ASC-US+), and cervical intraepithelial neoplasia grade 1, 2 or greater (CIN1+, CIN2+). For HPV-18, while seropositivity was associated with lower risk of ASC-US+ and CIN1+, no association between naturally-acquired antibodies and infection was demonstrated. Naturally-acquired HPV-16 antibody levels of 371 (95% confidence interval: 42-794), 204 (129-480) and 480 (250-5756) EU/mL were associated with 90% reduction of incident infection, 6-month persistent infection, and ASC-US+, respectively.Conclusions. Naturally-acquired antibodies to HPV-16, and to a lesser extent HPV-18, are associated with some reduced risk of subsequent infection and cervical abnormalities associated with the same HPV type.
    The Journal of Infectious Diseases 03/2014; DOI:10.1093/infdis/jiu139 · 5.78 Impact Factor
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    ABSTRACT: Epithelial ovarian cancers either arise directly from Mullerian-type epithelium or acquire Mullerian characteristics in the course of neoplastic transformation. The anti-Mullerian hormone (AMH) causes regression of Mullerian structures during fetal development in males and has been shown to inhibit the growth of epithelial ovarian cancer. Therefore, we hypothesized that pre-diagnostic serum concentrations of AMH are inversely associated with risk of invasive serous ovarian cancer. A case-control study (107 cases, 208 controls) was nested within the population-based Finnish Maternity Cohort (1986-2007). The sample donated during the first trimester of the last pregnancy preceding cancer diagnosis of the case subjects was selected for the study. For each case, two controls, matched on age and date at sampling, as well as parity at sampling and at cancer diagnosis were selected. AMH was measured by a second-generation AMH ELISA. Conditional logistic regression was used to compute odds ratios (OR) and 95 % confidence intervals (CI) for invasive serous ovarian cancer associated with AMH concentrations. Overall AMH concentrations were not associated with risk of invasive serous ovarian cancer (OR 0.93; 95 % CI 0.49-1.77 for top vs. bottom tertile, P trend = 0.83). In women older than the median age at sampling (32.7 years), a doubling of AMH was associated with decreased risk (OR 0.69; 95 % CI 0.49-0.96), whereas an increased risk (OR 1.64; 95 % CI 1.06-2.54) was observed in younger women, P homogeneity = 0.002. In this first prospective investigation, risk of invasive serous ovarian cancer was not associated with pre-diagnostic AMH concentrations overall; however, the association may depend on age at AMH measurement.
    Cancer Causes and Control 02/2014; DOI:10.1007/s10552-014-0363-9 · 2.96 Impact Factor
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    ABSTRACT: The distribution of Chlamydia trachomatis serotypes in the sexually active population may change over time. Serum from C. trachomatis seropositive women representing the 1980s, 1990s, and 2000s were available from a stratified random sample (11,067) of the Finnish Maternity Cohort for microimmunofluorescence-based classification. The C. trachomatis serotype distributions in the 1980s and 2000s were comparable, with serotypes G, E, and J being the most prevalent. In the 1990s the numbers of women seropositive for ≥ 2 serotypes peaked, and serotypes G/J were replaced by serotypes E/D. The temporary C. trachomatis serotype replacement parallels changes in the sexually active population in the 1990s in Finland.
    Scandinavian Journal of Infectious Diseases 02/2014; DOI:10.3109/00365548.2013.878031 · 1.64 Impact Factor
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    ABSTRACT: Cervical cancer continues to be an important public health problem in Thailand. While the high risk human papillomavirus (HPV) types have been established as the principle causative agent of both malignancies and the precursor lesions, cervical intraepithelial neoplasia (CIN), other factors may also be involved like other sexually transmitted diseases, as well as smoking. Chlamydia trachomatis is an obligate intracellular Gram-negative bacterium which has a tendency to cause chronic infection featuring inflammation and therefore might be expected to increase the risk of cervical cancer. In the present nested case-control study, 61 cases of cervical cancer and 288 matched controls with original serum samples were identified from the Khon Kaen Cohort, established in the North-East of Thailand, by linkage to the Khon Kaen population based cancer registry. C. trachomatis specific IgG antibodies at recruitment were measured by microimmunofluorescence and assessed for association with cervical cancer using STATA release10. No significant link was noted either with all cancers or after removal of adenocarcinomas. The results suggest no association between Chlamydia infection and cervical cancer development in North-East Thailand, but possible influencing factors must be considered in any future research on this topic.
    Asian Pacific journal of cancer prevention: APJCP 02/2014; 15(3):1497-1500. DOI:10.7314/APJCP.2014.15.3.1497 · 1.50 Impact Factor
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    ABSTRACT: More information is needed about time between sexual initiation and human papillomavirus (HPV) infection and development of cervical precancer. The objectives were to investigate the time between first sexual activity and detection of first cervical HPV infection or development of first cervical intraepithelial neoplasia (CIN), and associated factors in women from the double-blind, multinational, 4-year PATRICIA trial. PATRICIA enroled women aged 15-25 years with no more than 6 lifetime sexual partners. Women were randomized 1:1 to the HPV-16/18 AS04-adjuvanted vaccine or to control, but only women from the control arm who began sexual intercourse during the study or within 6 months before enrolment, and had no HPV infection detected before the recorded date of their first sexual intercourse, were included in the present analysis. The time between onset of sexual activity and detection of the first cervical HPV infection or development of the first CIN lesion was analyzed using Kaplan-Meier and univariate and multivariable Cox proportional-hazards models. A total of 9337 women were enroled in the control arm of PATRICIA of whom 982 fulfilled the required inclusion criteria for analysis. A cumulative total of 28%, 44%, and 62% of the subjects had HPV infection within 12, 24, and 48 months, respectively. The overall incidence rate was 27.08 per 100 person-years. The most common oncogenic types associated with 6-month persistent infection were HPV-16 (incidence rate: 2.74 per 100 person-years), HPV-51 (2.70), HPV-52 (1.66), HPV-66 (1.14), and HPV-18 (1.09). Increased infection risk was associated with more lifetime sexual partners, being single, Chlamydia trachomatis history, and duration of hormone use. CIN1+ and CIN2+ lesions were most commonly associated with HPV-16, with an overall incidence rate of 1.87 and 1.07 per 100 person-years, respectively. Previous cervical HPV infection was most strongly associated with CIN development. More than 25% of women were infected with HPV within 1 year of beginning sexual activity. Without underestimating the value of vaccination at older ages, our findings emphasize its importance before sexual initiation. clinicaltrials.gov: NCT00122681 .
    BMC Infectious Diseases 01/2014; 14(1):551. DOI:10.1186/s12879-014-0551-y · 2.56 Impact Factor
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    ABSTRACT: We aimed to develop and evaluate the effectiveness of an individualized, long-term support lifestyle counseling approach in promoting healthy physical activity, improving dietary and sleeping behaviors, and preventing weight gain in young females. The counseling approach's intensity was designed to be low enough to be implementable in primary health care. Young women (n = 3,059, age at baseline 17--21 years) attending a population-based human papilloma virus vaccination trial (clinicaltrials.gov identifier: NCT00122681) in 15 vaccination centers in different communities across Finland, were cluster-randomized into intervention and control arms of the LINDA intervention. Both intervention and control arms received counseling on sexual health and contraception from the study nurses as part of the vaccination trial. Additionally, the LINDA intervention arm (n = 1,537) received a 20-minute individualized lifestyle counseling session followed by further support at the six-monthly follow-up visits of the vaccination trial, in total for 1.5[box drawings light horizontal]2.5 years.The LINDA solution-focused brief therapy intervention focused on healthy physical activity, and dietary and sleeping behaviors, based on the needs and interests of the participants. Anthropometrics were measured, and data on health-related behaviors were collected using self-report questionnaires at baseline and after the intervention at 1.5[box drawings light horizontal]2.5 years. In the intervention arm, 37% vs. 31% in the control arm made an overall improvement in their health behaviors concerning physical activity, meal regularity and/or earlier bedtime (NNT = 18, 95% CI = 11[box drawings light horizontal]50). The per-protocol analysis further revealed that 30% of those who actually received lifestyle change support on healthy physical activity behaviors improved their physical activity level vs. 23% in the control group (NNT = 15, 95% CI = 9[box drawings light horizontal]38). Respectively, 36% of those who received support on healthy sleeping behaviors went to sleep earlier before school-/work-days after the intervention vs. 28% in the control group (NNT = 13, 95% CI = 7[box drawings light horizontal]61). Dinner irregularity increased in both groups, but less in the intervention group among those who received support on healthy dietary behaviors (NNT = 15, 95%CI = 9[box drawings light horizontal]46). There was no effect on weight gain between baseline and study end-point. The solution-focused brief therapy intervention, with individually tailored content, helped to make small, long-term overall improvements in health behaviors concerning physical activity, meal regularity and/or earlier bedtime.
    BMC Public Health 11/2013; 13(1):1044. DOI:10.1186/1471-2458-13-1044 · 2.32 Impact Factor
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    ABSTRACT: Background. Public Health England has reported a decrease of up to 20.8% in new diagnoses of external genital warts (GWs) among women aged <19 years since the national vaccination program with the human papillomavirus (HPV)-16/18 AS04-adjuvanted vaccine began in 2008. A post hoc analysis of the phase III PATRICIA (PApilloma TRIal against Cancer In young Adults) trial (NCT00122681) was performed to ascertain whether protection against low-risk HPV types was apparent. Methods. Vaccine efficacy (VE) at 48 months was assessed against 6-month persistent infection (6MPI) with low-risk HPV types in the total vaccinated cohort (TVC) and in the TVC naive (for 25 HPV types tested) populations. Results. In the TVC naive cohort, VE against 6MPI (95% confidence interval) was 34.5% (11.3 to 51.8) for HPV-6/11, 34.9% (9.1 to 53.7) for HPV-6, 30.3% (-45.0 to 67.5) for HPV-11, and 49.5% (21.0 to 68.3) for HPV-74. Conclusions. The HPV-16/18 AS04-adjuvanted vaccine appears to have moderate efficacy against persistent infections with a number of low-risk HPV types (HPV-6/11/74), which are responsible for the majority of external GWs, and recently, antibody and cell-mediated immune response to HPV-6/11 have been observed. These findings may help to explain the decrease in external GW diagnoses seen in England.
    The Journal of Infectious Diseases 11/2013; 208(9):1391-1396. DOI:10.1093/infdis/jit360 · 5.78 Impact Factor
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    ABSTRACT: Interactions of carcinogenic human papillomaviruses (most notably HPV types 16/18/31/33/45), and HPV6 or Chlamydia trachomatis are not well understood. We have used seroconversions to study effects the order of these infections has on the risk of high-grade cervical precancer. In a cohort of 94,349 Finnish women with paired sera from consecutive pregnancies within an average of 2.4 years, 490 were diagnosed with cervical CIN3/AIS. Serum antibodies to HPV6/16/18/31/33/45 and C.trachomatis were also measured in paired sera of a subcohort of 2,796 women with a minimum of two pregnancies. HPV16-adjusted rate ratios (RR) and confidence intervals were estimated by stratified Cox model. Compared to dual seropositivity already at the first serum sampling, RRs related to HPV6 seropositivity before and after HPV31 seroconversion were 0.4 (95% CI 0.0,4.4) and 10 (95% CI 1.8,57). Furthermore, RR related to seroconversions of both HPV18/45 and C.trachomatis between the consecutive pregnancies was 28 (95% CI 4.3,190). Virtually concomitant HPV18/45 and C.trachomatis infections are associated with very high CIN3 risk. © 2013 Wiley Periodicals, Inc.
    International Journal of Cancer 10/2013; 133(7). DOI:10.1002/ijc.28173 · 5.01 Impact Factor
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    ABSTRACT: The aim of this study was to evaluate the total burden and health care provider costs of prevention, management and treatment of HP- related genital disease outcomes including all organised and opportunistic screening tests. Information about HPV-related disease outcomes in the Finnish female population of 2.7 million was obtained from nationwide population-based registry data. We estimated the incidence, health care resource use, health provider costs and life-years lost due to cervical, vaginal and vulvar cancer and intraepithelial neoplasia (CIN, VaIN, VIN), cervical adenocarcinoma in situ (AIS), and external genital warts. The average annual disease burden of HPV-related genital disease in the female population of Finland comprises altogether 241 cases of cervical, vaginal and vulvar cancer, 2 898 new cases of CIN, 34 432 cases of minor cytological abnormalities, and almost 4 000 cases of external genital warts. The total annual costs of screening, further diagnostics and treatment of HPV-related genital disease were €44.7 million of which the annual costs due to cervical cancer screening were €22.4 million and due to diagnostics, management and treatment of HPV-related genital disease outcomes were €22.3 million. The latter included €8.4 million due to minor cervical abnormalities detected by the current cervical screening practice. The extensive opportunistic Pap testing fails to keep the incidence of cervical cancer from increasing among women aged 30-34. In addition opportunistic screening among this and younger age group detects a significant number of cytological abnormalities, most of which are probably treated unnecessarily. © 2013 Wiley Periodicals, Inc.
    International Journal of Cancer 09/2013; 133(6). DOI:10.1002/ijc.28145 · 5.01 Impact Factor
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    ABSTRACT: The development of high-risk human papillomavirus (hrHPV) infection to cervical cancer is a complicated process. We considered solely hrHPV infections, thus avoiding the confounding effects of disease progression, screening, and treatments. To analyse hrHPV epidemiology and to estimate the overall impact of vaccination against infections with hrHPVs, we developed a dynamic compartmental transmission model for single and multiple infections with 14 hrHPV types. The infection-related parameters were estimated using population-based sexual behaviour and hrHPV prevalence data from Finland. The analysis disclosed the important role of persistent infections in hrHPV epidemiology, provided further evidence for a significant natural immunity, and demonstrated the dependence of transmission probability estimates on the model structure. The model predicted that vaccinating girls at 80% coverage will result in a 55% reduction in the overall hrHPV prevalence and a higher 65% reduction in the prevalence of persistent hrHPV infections in females. In males, the reduction will be 42% in the hrHPV prevalence solely by the herd effect from the 80% coverage in girls. If such high coverage among girls is not reached, it is still possible to reduce the female hrHPV prevalence indirectly by the herd effect if also boys are included in the vaccination program. On the other hand, any herd effects in older unvaccinated cohorts were minor. Limiting the epidemiological model to infection yielded improved understanding of the hrHPV epidemiology and of mechanisms with which vaccination impacts on hrHPV infections.
    PLoS ONE 08/2013; 8(8):e72088. DOI:10.1371/journal.pone.0072088 · 3.53 Impact Factor
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    ABSTRACT: Objectives Genital human papillomavirus (HPV) infections and associated precancerous lesions adversely affect health-related quality of life (HRQoL). HPV vaccines provide effective protection against these conditions. We therefore investigated the impact of HPV vaccination on HRQoL in young women five years after participation in a phase III HPV vaccination trial. Methods A total of 4808 originally 16- to 17-year-old Finnish girls had participated in the PATRICIA trial and received either bivalent HPV 16/18 vaccine or hepatitis A-virus (HAV) vaccine in 2004 to 2005. Unvaccinated girls (n = 9602), from adjacent birth cohorts, had participated in the control cohort in 2005. From 2009 to 2011, at 22 to 23 years of age, all participants received a questionnaire consisting of two generic HRQoL instruments (RAND36 and EQ VAS) and a disease-specific questionnaire (CECA10). Results We analysed responses of 1143 HPV 16/18-vaccinated, 980 HAV-vaccinated, and 3753 unvaccinated young women. The unadjusted mean outcome measures of the different HRQoL estimates were similar in the three different responder cohorts. Conclusions Five years after vaccination the health-related quality of life of HPV 16/ 18- vaccinated young women did not differ from those of HAV-vaccinated or unvaccinated controls representing the general population.
    The European Journal of Contraception and Reproductive Health Care 06/2013; DOI:10.3109/13625187.2013.801953 · 1.84 Impact Factor

Publication Stats

10k Citations
1,322.92 Total Impact Points

Institutions

  • 1983–2015
    • University of Tampere
      • • School of Health Sciences
      • • Department of Public Health
      • • Department of Biomedical Sciences
      • • Institute of Biomedical Sciences
      Tammerfors, Pirkanmaa, Finland
  • 2009–2013
    • National Institute for Health and Welfare, Finland
      • • Department of Vaccination and Immune Protection
      • • Child and Adolescent Mental Health Unit
      Helsinki, Southern Finland Province, Finland
    • Danderyds Sjukhus AB
      Tukholma, Stockholm, Sweden
    • Danish Cancer Society
      København, Capital Region, Denmark
  • 2011
    • University of Lausanne
      • Institute of Social and Preventive Medicine
      Lausanne, Vaud, Switzerland
  • 2010
    • Kuopio University Hospital
      • Department of Obstetrics and Gynaecology
      Kuopio, Province of Eastern Finland, Finland
  • 1994–2010
    • National Public Health Institute
      Helsinki, Southern Finland Province, Finland
  • 2002–2007
    • Lund University
      Lund, Skåne, Sweden
  • 1996–2006
    • University of Helsinki
      • • Department of Obstetrics and Gynaecology
      • • Department of Virology
      Helsinki, Province of Southern Finland, Finland
  • 2005
    • Malmö University
      Malmö, Skåne, Sweden
  • 1998–2005
    • Finnish Cancer Registry, Helsinki
      Helsinki, Southern Finland Province, Finland
  • 1997–2001
    • Cancer Registry of Norway
      • Department of Research
      Kristiania (historical), Oslo County, Norway
    • Karolinska Institutet
      Solna, Stockholm, Sweden
  • 1991–1994
    • Helsinki University Central Hospital
      • Department of Obstetrics and Gynaecology
      Helsinki, Province of Southern Finland, Finland
  • 1990
    • Tampere University Hospital (TAUH)
      Tammerfors, Province of Western Finland, Finland
  • 1980
    • Central Hospital Central Finland
      Jyväskylä, Province of Western Finland, Finland