Jorma Paavonen

Publications (129)587.67 Total impact

• Article: Cervical cancer incidence can increase despite HPV vaccination.

  Diane M Harper, Pekka Nieminen, Jorma Paavonen, Matti Lehtinen
  The Lancet Infectious Diseases 09/2010; 10(9):594-5; author reply 595. · 17.39 Impact Factor
• Source

  Available from: Elmar A Joura

  Article: Incidence, duration, and reappearance of type-specific cervical human papillomavirus infections in young women.

  Ralph P Insinga, Gonzalo Perez, Cosette M Wheeler, Laura A Koutsky, Suzanne M Garland, Sepp Leodolter, Elmar A Joura, Daron G Ferris, Marc Steben, Darron R Brown, Elamin H Elbasha, Jorma Paavonen, Richard M Haupt
  [show abstract] [hide abstract]
  ABSTRACT: We describe the incidence and duration of cervical human papillomavirus (HPV) infection episodes along with the risk of infection reappearance following a period of nondetection. Women (1,788) ages 16 to 23 years underwent cytologic testing and PCR-based testing of cervical swab samples for HPV DNA (HPV-16/18/31/33/35/45/52/58/59) at approximately 6-month intervals for up to 4 years in the context of a phase 3 clinical trial (placebo arm). HPV type-specific incidence rates were estimated per 100 person-years. Duration of type-specific cervical infection episodes and risk of reappearance following a period of nondetection were estimated using Kaplan-Meier methods. HPV-16 exhibited the highest (5.9), and HPV-35 and HPV-33 exhibited the lowest (1.0) incidence rates per 100 person-years. Mean cervical infection durations ranged from 13 months for HPV-59 to 20 months for HPV-16 and 58 (with ongoing infections censored at the time of treatment, if done). The risk of cervical infection reappearance within approximately 3 years following a period of nondetection ranged from 0% to 16% across HPV types, with a mean of 8%. Limited evidence was found for a role of false-positive HPV tests, missed infections that were above the threshold for detection, or new acquisition of infection in accounting for patterns of infection reappearance. Incidence of high-risk cervical infection was observed to vary considerably more across HPV types than infection duration. A nontrivial proportion of women exhibited infection reappearance following a period of nondetection, with a potential explanation for many such events observed within this analysis being a return to detectable levels of a previously acquired infection. The risk of HPV infection reappearance following a period of nondetection has not been previously reported for individual HPV types, and this study finds that a nontrivial proportion of infected women exhibit reappearances. Future studies could ascertain subject-level factors that potentially modify the risk of infection reappearance.
  Cancer Epidemiology Biomarkers &amp Prevention 06/2010; 19(6):1585-94. · 4.12 Impact Factor
• Article: Male fetal sex is associated with earlier onset of placental abruption.

  Minna Tikkanen, Marjo Metsäranta, Mika Gissler, Tiina Luukkaala, Vilho Hiilesmaa, Olavi Ylikorkala, Jorma Paavonen, Sture Andersson, Mika Nuutila
  [show abstract] [hide abstract]
  ABSTRACT: Placental abruption is an important cause of preterm birth, and perinatal morbidity and mortality. Although more common with male fetuses, outcomes have not been evaluated by sex. Our aim was to find out whether short-term morbidity differs by infant sex in cases with placental abruption and in controls. Register-based case-control study. National Hospital Discharge Register and Medical Birth Register data 1987-2005. The study population consisted of 4,081 women with placental abruption and singleton infant. Three control women without placental abruption were selected for each case matched by maternal age, parity, year of birth, and hospital district. A total of 3,688 cases and 12,695 controls had liveborn infants. Data on pregnancy, delivery, and perinatal outcomes were collected. Placental abruption. The sex ratio (proportion of male) of cases was 0.548 and of controls 0.516 (p = 0.001). Compared with females, male fetuses in the placental abruption group were born earlier (p = 0.018). Compared with controls, cases with placental abruption were born earlier (p < 0.001), had lower birthweight (p < 0.001), were more often growth restricted (p < 0.001), had lower Apgar scores (p < 0.001) and pH (p < 0.001). Newborn cases needed special care, respirator treatment, antimicrobial and phototherapy more often (p < 0.001) than controls. There was no difference in perinatal outcomes between female and male infants in the placental abruption group. Placental abruption occurred earlier in pregnancy with male fetal sex but otherwise the outcomes were similar. Compared with controls newborns in the placental abruption group had a worse outcome.
  Acta Obstetricia Et Gynecologica Scandinavica 03/2010; 89(7):916-23. · 1.77 Impact Factor
• Source

  Available from: Grace W K Tang

  Article: Impact of human papillomavirus (HPV)-6/11/16/18 vaccine on all HPV-associated genital diseases in young women.

  Nubia Muñoz, Susanne K Kjaer, Kristján Sigurdsson, Ole-Erik Iversen, Mauricio Hernandez-Avila, Cosette M Wheeler, Gonzalo Perez, Darron R Brown, Laura A Koutsky, Eng Hseon Tay, [......], Christine Roberts, Amha Tadesse, Janine T Bryan, Lisa C Lupinacci, Katherine E D Giacoletti, Heather L Sings, Margaret K James, Teresa M Hesley, Eliav Barr, Richard M Haupt
  [show abstract] [hide abstract]
  ABSTRACT: The impact of the prophylactic vaccine against human papillomavirus (HPV) types 6, 11, 16, and 18 (HPV6/11/16/18) on all HPV-associated genital disease was investigated in a population that approximates sexually naive women in that they were "negative to 14 HPV types" and in a mixed population of HPV-exposed and -unexposed women (intention-to-treat group). This analysis studied 17 622 women aged 15-26 years who were enrolled in one of two randomized, placebo-controlled, efficacy trials for the HPV6/11/16/18 vaccine (first patient on December 28, 2001, and studies completed July 31, 2007). Vaccine or placebo was given at day 1, month 2, and month 6. All women underwent cervicovaginal sampling and Papanicolaou (Pap) testing at day 1 and every 6-12 months thereafter. Outcomes were any cervical intraepithelial neoplasia; any external anogenital and vaginal lesions; Pap test abnormalities; and procedures such as colposcopy and definitive therapy. Absolute rates are expressed as women with endpoint per 100 person-years at risk. The average follow-up was 3.6 years (maximum of 4.9 years). In the population that was negative to 14 HPV types, vaccination was up to 100% effective in reducing the risk of HPV16/18-related high-grade cervical, vulvar, and vaginal lesions and of HPV6/11-related genital warts. In the intention-to-treat group, vaccination also statistically significantly reduced the risk of any high-grade cervical lesions (19.0% reduction; rate vaccine = 1.43, rate placebo = 1.76, difference = 0.33, 95% confidence interval [CI] = 0.13 to 0.54), vulvar and vaginal lesions (50.7% reduction; rate vaccine = 0.10, rate placebo = 0.20, difference = 0.10, 95% CI = 0.04 to 0.16), genital warts (62.0% reduction; rate vaccine = 0.44, rate placebo = 1.17, difference = 0.72, 95% CI = 0.58 to 0.87), Pap abnormalities (11.3% reduction; rate vaccine = 10.36, rate placebo = 11.68, difference = 1.32, 95% CI = 0.74 to 1.90), and cervical definitive therapy (23.0% reduction; rate vaccine = 1.97, rate placebo = 2.56, difference = 0.59, 95% CI = 0.35 to 0.83), irrespective of causal HPV type. High-coverage HPV vaccination programs among adolescents and young women may result in a rapid reduction of genital warts, cervical cytological abnormalities, and diagnostic and therapeutic procedures. In the longer term, substantial reductions in the rates of cervical, vulvar, and vaginal cancers may follow.
  CancerSpectrum Knowledge Environment 02/2010; 102(5):325-39. · 14.07 Impact Factor
• Source

  Available from: Grace W K Tang

  Article: Four year efficacy of prophylactic human papillomavirus quadrivalent vaccine against low grade cervical, vulvar, and vaginal intraepithelial neoplasia and anogenital warts: randomised controlled trial.

  Joakim Dillner, Susanne K Kjaer, Cosette M Wheeler, Kristján Sigurdsson, Ole-Erik Iversen, Mauricio Hernandez-Avila, Gonzalo Perez, Darron R Brown, Laura A Koutsky, Eng Hseon Tay, [......], Frank J Taddeo, Christine Roberts, Amha Tadesse, Janine T Bryan, Roger Maansson, Shuang Lu, Scott Vuocolo, Teresa M Hesley, Eliav Barr, Richard Haupt
  [show abstract] [hide abstract]
  ABSTRACT: To evaluate the prophylactic efficacy of the human papillomavirus (HPV) quadrivalent vaccine in preventing low grade cervical, vulvar, and vaginal intraepithelial neoplasias and anogenital warts (condyloma acuminata). Data from two international, double blind, placebo controlled, randomised efficacy trials of quadrivalent HPV vaccine (protocol 013 (FUTURE I) and protocol 015 (FUTURE II)). The trials were to be 4 years in length, and the results reported are from final study data of 42 months' follow-up. Primary care centres and university or hospital associated health centres in 24 countries and territories around the world. 17 622 women aged 16-26 years enrolled between December 2001 and May 2003. Major exclusion criteria were lifetime number of sexual partners (>4), history of abnormal cervical smear test results, and pregnancy. Three doses of quadrivalent HPV vaccine (for serotypes 6, 11, 16, and 18) or placebo at day 1, month 2, and month 6. Vaccine efficacy against cervical, vulvar, and vaginal intraepithelial neoplasia grade I and condyloma in a per protocol susceptible population that included subjects who received all three vaccine doses, tested negative for the relevant vaccine HPV types at day 1 and remained negative through month 7, and had no major protocol violations. Intention to treat, generally HPV naive, and unrestricted susceptible populations were also studied. In the per protocol susceptible population, vaccine efficacy against lesions related to the HPV types in the vaccine was 96% for cervical intraepithelial neoplasia grade I (95% confidence interval 91% to 98%), 100% for both vulvar and vaginal intraepithelial neoplasia grade I (95% CIs 74% to 100%, 64% to 100% respectively), and 99% for condyloma (96% to 100%). Vaccine efficacy against any lesion (regardless of HPV type) in the generally naive population was 30% (17% to 41%), 75% (22% to 94%), and 48% (10% to 71%) for cervical, vulvar, and vaginal intraepithelial neoplasia grade I, respectively, and 83% (74% to 89%) for condyloma. Quadrivalent HPV vaccine provided sustained protection against low grade lesions attributable to vaccine HPV types (6, 11, 16, and 18) and a substantial reduction in the burden of these diseases through 42 months of follow-up. NCT00092521 and NCT00092534.
  BMJ (Clinical research ed.). 01/2010; 341:c3493.
• Article: Cost effectiveness of prophylactic HPV 16/18 vaccination in Finland: results from a modelling exercise.

  Saku Torvinen, Pekka Nieminen, Matti Lehtinen, Jorma Paavonen, Nadia Demarteau, Jarmo Hahl
  [show abstract] [hide abstract]
  ABSTRACT: the study aims to estimate the clinical-impact and cost-effectiveness value of adding human papillomavirus 16/18 vaccination against cervical cancer among women currently undergoing organised screening in Finland. A Markov cohort model evaluating high-risk HPV infections and cervical cancer (CC) cases combined with screening has been customised to the Finnish setting. The model outcome for a cohort of 30,000 girls aged 10 years was calibrated to age-specific annual number of Pap smears, CC incidence and mortality. The observed age-specific incidence and mortality rates of CC closely match the data replicated by the model. The model predicts that with a 90% vaccine coverage rate, CC cases and mortality would be reduced by 70%. In the base-case analysis with a discount rate of 3% the incremental cost per quality-adjusted life-years (QALY) gained, from a healthcare perspective, was €17,294. Without discounting this value is €2,591/QALY gained. The analysis suggests that implementing prophylactic CC vaccination within the current screening system would substantially reduce CC cases and deaths, as well as the overall disease burden expressed in pre-cancer lesions averted. Vaccination could be a cost-effective intervention in Finland despite the fact that the number of CC cases and deaths are currently relatively low. Conservative estimates of the cost effectiveness of the vaccination were provided since it was not possible to assess herd protection induced by vaccination using this Markov model.
  Journal of Medical Economics 01/2010; 13(2):284-94.
• Source

  Available from: Kevin A Ault

  Article: Pregnancy and infant outcomes in the clinical trials of a human papillomavirus type 6/11/16/18 vaccine: a combined analysis of five randomized controlled trials.

  Suzanne M Garland, Kevin A Ault, Stanley A Gall, Jorma Paavonen, Heather L Sings, Karen L Ciprero, Alfred Saah, Deborah Marino, Desmond Ryan, David Radley, Haiping Zhou, Richard M Haupt, Elizabeth I O Garner
  [show abstract] [hide abstract]
  ABSTRACT: To present a combined analysis of the pregnancy outcomes for women aged up to 45 years enrolled in five phase III clinical studies of the prophylactic quadrivalent human papillomavirus 6/11/16/18 vaccine. Twenty thousand five hundred fifty-one women aged 15-45 years received quadrivalent HPV vaccine or placebo at day 1 and months 2 and 6. Urine pregnancy tests were performed immediately before each injection; participants testing positive were not vaccinated. Women who became pregnant after enrollment were discontinued from further vaccination until resolution of pregnancy. All pregnancies were followed for outcomes. During the studies, 1,796 vaccine and 1,824 placebo recipients became pregnant, resulting in 2,008 and 2,029 pregnancies with known outcomes. No significant differences were noted overall for the proportions of pregnancies resulting in live birth, fetal loss, or spontaneous abortion. A total of 40 neonates born to vaccinated women and 30 neonates born to women given placebo had one or more congenital anomalies (P=.20). The anomalies were diverse and consistent with those most commonly observed in the general population. The vaccine was well tolerated among women who became pregnant. Administration of quadrivalent human papillomavirus vaccine to women who became pregnant during the phase III clinical trials did not appear to negatively affect pregnancy outcomes. The vaccine is a U.S. Food and Drug Administration pregnancy category B medication (animal studies revealed no evidence of fetal harm, but there are no adequate and well-controlled studies in pregnant women); however, vaccination is not recommended during pregnancy. Postlicensure surveillance is ongoing. ClinicalTrials.gov, www.clinicaltrials.gov, NCT00092521, NCT00092534, NCT00092495, NCT00092547 and NCT00090220. II.
  Obstetrics and Gynecology 12/2009; 114(6):1179-88. · 4.73 Impact Factor
• Article: The effect of hysterectomy or levonorgestrel-releasing intrauterine system on lower abdominal pain and back pain among women treated for menorrhagia: a five-year randomized controlled trial.

  Satu Heliövaara-Peippo, Karoliina Halmesmäki, Ritva Hurskainen, Juha Teperi, Seija Grenman, Aarre Kivelä, Erkki Kujansuu, Marjo Tuppurainen, Sirkku Vuorma, Merja Yliskoski, Jorma Paavonen
  [show abstract] [hide abstract]
  ABSTRACT: The purpose of this study was to evaluate the changes in lower abdominal pain and back pain among women with menorrhagia treated by hysterectomy or levonorgestrel-releasing intrauterine system (LNG-IUS). A randomized controlled trial. Five university hospitals in Finland. A total of 236 women, aged 35-49 years. Women were randomly assigned to treatment by hysterectomy (n = 117) or LNG-IUS (n = 119). Frequency and intensity of lower abdominal pain and back pain were evaluated by questionnaires at baseline and after 6 months, 12 months and 5 years. By six months, women in both groups had less frequent back pain than before treatment (p < 0.001). Lower abdominal pain decreased only in the hysterectomy group (p = 0.02) with significant differences between the groups. Between 12 months and 5 years, frequency of lower abdominal pain (p = 0.05) and back pain (p = 0.002) decreased more in the LNG-IUS group than in the hysterectomy group. Between baseline and five years, the lower abdominal pain score (including frequency and intensity of pain) decreased in both groups (p < 0.001, p = 0.01). Back pain score decreased only in the LNG-IUS group and the difference between the groups was significant (p = 0.02). However, some women experienced more pain after both treatments than before treatment. In multivariate analyses, LNG-IUS use was associated with a decrease in lower abdominal pain and back pain. In the treatment of menorrhagia, both hysterectomy and LNG-IUS decrease lower abdominal pain. LNG-IUS use, but not hysterectomy, has beneficial effects on back pain.
  Acta Obstetricia Et Gynecologica Scandinavica 11/2009; 88(12):1389-96. · 1.77 Impact Factor
• Source

  Available from: Elmar A Joura

  Article: A pooled analysis of continued prophylactic efficacy of quadrivalent human papillomavirus (Types 6/11/16/18) vaccine against high-grade cervical and external genital lesions.

  Susanne K Kjaer, Kristján Sigurdsson, Ole-Erik Iversen, Mauricio Hernandez-Avila, Cosette M Wheeler, Gonzalo Perez, Darron R Brown, Laura A Koutsky, Eng Hseon Tay, Patricia García, [......], Christine Roberts, Amha Tadesse, Janine Bryan, Roger Maansson, Shuang Lu, Scott Vuocolo, Teresa M Hesley, Alfred Saah, Eliav Barr, Richard M Haupt
  [show abstract] [hide abstract]
  ABSTRACT: Quadrivalent human papillomavirus (HPV) vaccine has been shown to provide protection from HPV 6/11/16/18-related cervical, vaginal, and vulvar disease through 3 years. We provide an update on the efficacy of the quadrivalent HPV vaccine against high-grade cervical, vaginal, and vulvar lesions based on end-of-study data from three clinical trials. Additionally, we stratify vaccine efficacy by several baseline characteristics, including age, smoking status, and Papanicolaou (Pap) test results. A total of 18,174 females ages 16 to 26 years were randomized and allocated into one of three clinical trials (protocols 007, 013, and 015). Vaccine or placebo was given at baseline, month 2, and month 6. Pap testing was conducted at regular intervals. Cervical and anogenital swabs were collected for HPV DNA testing. Examination for the presence of vulvar and vaginal lesions was also done. Endpoints included high-grade cervical, vulvar, or vaginal lesions (CIN 2/3, VIN 2/3, or VaIN 2/3). Mean follow-up time was 42 months post dose 1. Vaccine efficacy against HPV 6/11/16/18-related high-grade cervical lesions in the per-protocol and intention-to-treat populations was 98.2% [95% confidence interval (95% CI), 93.3-99.8] and 51.5% (95% CI, 40.6-60.6), respectively. Vaccine efficacy against HPV 6/11/16/18-related high-grade vulvar and vaginal lesions in the per-protocol and intention-to-treat populations was 100.0% (95% CI, 82.6-100.0) and 79.0% (95% CI, 56.4-91.0), respectively. Efficacy in the intention-to-treat population tended to be lower in older women, women with more partners, and women with abnormal Pap test results. The efficacy of quadrivalent HPV vaccine against high-grade cervical and external anogenital neoplasia remains high through 42 months post vaccination.
  Cancer Prevention Research 10/2009; 2(10):868-78. · 4.91 Impact Factor
• Article: Evaluation of quadrivalent HPV 6/11/16/18 vaccine efficacy against cervical and anogenital disease in subjects with serological evidence of prior vaccine type HPV infection.

  Sven-Eric Olsson, Susanne K Kjaer, Kristján Sigurdsson, Ole-Erik Iversen, Mauricio Hernandez-Avila, Cosette M Wheeler, Gonzalo Perez, Darron R Brown, Laura A Koutsky, Eng Hseon Tay, [......], Frank J Taddeo, Christine Roberts, Amha Tadesse, Janine Bryan, Roger Maansson, Scott Vuocolo, Teresa M Hesley, Alfred Saah, Eliav Barr, Richard M Haupt
  [show abstract] [hide abstract]
  ABSTRACT: In the quadrivalent (types 6/11/16/18) HPV vaccine (GARDASIL/SILGARD) clinical program, 73% of women aged 16-26 were naïve to all vaccine HPV types. In these women, prophylactic administration of the vaccine was highly effective in preventing HPV 6/11/16/18-related cervical disease. Of the remaining women, 15% of had evidence of past infection with one or more vaccine HPV types (seropositive and DNA negative) at the time of enrollment. Here we present an analysis in this group of women to determine the efficacy of the HPV 6/11/16/18 vaccine against new cervical and external anogenital disease related to the same vaccine HPV type which had previously been cleared. Vaccine tolerability in this previously infected population was also assessed. 18,174 women were enrolled into 3 clinical studies. The data presented comprise a subset of these subjects (n = 2,617) who were HPV seropositive and DNA negative at enrollment (for >or=1 vaccine type). In each study, subjects were randomized in a 1:1 ratio to receive HPV 6/11/16/18 vaccine or placebo at day 1, month 2 and month 6 (without knowledge of baseline HPV status). Procedures performed for efficacy data evaluation included detailed genital examination, Pap testing, and collection of cervicovaginal and external genital specimens. Analyses of efficacy were carried out in a population stratified by HPV serology and HPV DNA status at enrollment. Subjects were followed for an average of 40 months. Seven subjects in the placebo group developed cervical disease, and eight subjects developed external genital disease related to a vaccine HPV type they had previously encountered. No subject receiving HPV 6/11/16/18 vaccine developed disease to a vaccine HPV type to which they were seropositive and DNA negative at enrolment. These results suggest that natural HPV infection-elicited antibodies may not provide complete protection over time, however the immune response to the HPV 6/11/16/18 vaccine appears to prevent reinfection or reactivation of disease with vaccine HPV types. Vaccine-related adverse experiences were higher among subjects receiving vaccine, mostly due to increased injection site adverse experiences.
  Human vaccines 10/2009; 5(10):696-704. · 3.58 Impact Factor
• Source

  Available from: uc.edu

  Article: Loop electrosurgical excision procedure and the risk for preterm birth.

  Maija Jakobsson, Mika Gissler, Jorma Paavonen, Anna-Maija Tapper
  [show abstract] [hide abstract]
  ABSTRACT: To study whether loop electrosurgical excision procedure (LEEP) conization is associated with preterm birth and to study the effect of cone size on preterm birth. This was a retrospective cohort study from Southern Finland conducted from 1997 to 2003, with a follow-up for subsequent births until 2006. We identified the cases from the Hospital Discharge Register and Medical Birth Register and collected additional information from the hospital records. Our cohort consisted of 624 women who delivered after LEEP conization. We calculated expected preterm birth rates by using the Medical Birth Register data. In subgroup analysis (n=258 women) we used internal controls, ie, deliveries before the treatment. The main outcome measure was preterm birth rate in different subgroups. The risk for preterm delivery (before 37 weeks) was increased almost threefold (relative risk [RR] 2.61, 95% confidence interval [CI] 2.02-3.20; number needed to treat for harm=14) and repeat treatments more than fivefold (RR 5.15, 95% CI 2.45-7.84; number needed to treat for harm=5) after LEEP conization compared with the background rate of preterm birth (4.61%). Large or repeat cones increased the risk twofold (RR 2.45, 95% CI 1.38-3.53) when compared with small or medium-sized cones. For women having a birth before and after LEEP conization, the preterm birth rate was 6.5% before and 12.0% after the procedure (RR 1.94, 95% CI 1.10-3.40; number needed to treat for harm=18). Adjusting for maternal age, parity, or both did not change the results. The risk for preterm birth was especially increased (RR 3.38, 95% CI 2.31-4.94) among women without previous preterm birth. Loop electrosurgical excision procedure surgery of the cervix predisposes patients to preterm birth. Loop electrosurgical excision procedure conization increased the risk for preterm birth especially among women without previous preterm birth. The rates were highest after repeat procedures. II.
  Obstetrics and Gynecology 10/2009; 114(3):504-10. · 4.73 Impact Factor
• Article: Maternal deaths in Finland: focus on placental abruption.

  Minna Tikkanen, Mika Gissler, Marjo Metsäranta, Tiina Luukkaala, Vilho Hiilesmaa, Sture Andersson, Olavi Ylikorkala, Jorma Paavonen, Mika Nuutila
  [show abstract] [hide abstract]
  ABSTRACT: OBJECTIVE. To study placental abruption-associated maternal deaths out of all maternal deaths in Finland. DESIGN. Register-based study. SETTING. The Finnish Medical Birth Register (MBR), the Hospital Discharge Register (HDR), and the Cause-of-Death Register data during 1972-2005. METHODS. The maternal deaths were identified by linking data from the MBR, the HDR, and the Cause-of-Death Register. The clinical data were collected from the case records and death certificates. MAIN OUTCOME MEASURES. Cause-specific maternal death with special reference to placental abruption. RESULTS. During the study period, a total of 2,104,436 live births and 117 direct maternal deaths (caused by a disease or its management unique to the pregnancy) occurred in Finland. The direct maternal mortality ratio (MMR) was 5.6 per 100,000 live births. The two leading causes were thromboembolism (24.0%) and hemorrhage (22.3%) representing almost half of all maternal deaths. Altogether 7,735 placental abruptions were identified with three maternal deaths giving a case fatality rate of 0.4 per 1,000 cases. The MMR (38.8 per 100,000) was nearly seven times higher than the overall MMR (5.7 per 100,000) (p=0.010). CONCLUSION. The direct MMR in Finland is at the level generally seen in Western Europe. The main causes to maternal death are thromboembolism and obstetric hemorrhage. Deaths to placental abruption are rare, but still seven times higher than the overall MMR.
  Acta Obstetricia Et Gynecologica Scandinavica 09/2009; 88(10):1124-7. · 1.77 Impact Factor
• Article: Factors affecting matrix metalloproteinase-8 levels in the vaginal and cervical fluids in the first and second trimester of pregnancy.

  Leena Rahkonen, Eeva-Marja Rutanen, Leila Unkila-Kallio, Mika Nuutila, Pekka Nieminen, Timo Sorsa, Jorma Paavonen
  [show abstract] [hide abstract]
  ABSTRACT: Cervical ripening during pregnancy resembles an inflammatory process. Matrix metalloproteinases (MMPs), particularly MMP-8, have been linked to inflammatory processes. We studied the concentrations of, and factors associated with, MMP-8 in the lower genital tract fluids in the first and second trimesters. In a prospective population-based cohort study, vaginal and cervical swab samples were obtained from 2130 unselected pregnant women undergoing their first and second trimester ultrasound screening. MMP-8 was determined by immunofluorometric assay. Use of antibiotics, history of vaginal bleeding, and history of sexual intercourse were recorded on both occasions. Vaginal smears were obtained for Gram-staining and leukocyte counting. Cervical length was measured by ultrasonography. The main outcome measures were MMP-8 concentrations in the vagina and cervix. The median (range) MMP-8 concentrations in vaginal and cervical samples were 107.4 microg/l (undetectable-2406.6 microg/l) and 318.3 microg/l (0.1-2074.6 microg/l), respectively, in the first trimester, and 112.5 microg/l (undetectable-2093.4 microg/l) and 344.8 microg/l (0.4-1783.5 microg/l), respectively, in the second trimester. Multiparity and vaginal leukocytosis were both associated with increased MMP-8 concentrations in vaginal and cervical samples in both trimesters. Bacterial vaginosis (BV) was associated with increased vaginal and cervical MMP-8 in the first trimester, but only with increased vaginal MMP-8 in the second trimester. A history of sexual intercourse (in the previous 48 h) was associated with lower MMP-8 concentrations in cervical samples in both trimesters. MMP-8 concentrations were lower in vaginal samples than in cervical samples, and no difference was found between the first and second trimesters. Multiparity, BV and an elevated leukocyte count in the vagina were associated with increased MMP-8 concentrations. Sexual intercourse had an opposite effect. The study suggests that MMP-8 is a physiologic constituent in lower genital tract fluids, where it may be involved in host response to inflammatory and infectious processes.
  Human Reproduction 09/2009; 24(11):2693-702. · 4.47 Impact Factor
• Article: Impact of human papillomavirus vaccination depends on effective vaccination strategy.

  Matti Lehtinen, Jorma Paavonen
  International Journal of Cancer 05/2009; 125(6):1490-1. · 5.44 Impact Factor
• Source

  Available from: Grace W K Tang

  Article: The impact of quadrivalent human papillomavirus (HPV; types 6, 11, 16, and 18) L1 virus-like particle vaccine on infection and disease due to oncogenic nonvaccine HPV types in generally HPV-naive women aged 16-26 years.

  Darron R Brown, Susanne K Kjaer, Kristján Sigurdsson, Ole-Erik Iversen, Mauricio Hernandez-Avila, Cosette M Wheeler, Gonzalo Perez, Laura A Koutsky, Eng Hseon Tay, Patricía Garcia, [......], Frank J Taddeo, Christine Roberts, Amha Tadesse, Janine Bryan, Lisa C Lupinacci, Katherine E D Giacoletti, Heather L Sings, Margaret James, Teresa M Hesley, Eliav Barr
  [show abstract] [hide abstract]
  ABSTRACT: Human papillomavirus (HPV)-6/11/16/18 vaccine reduces the risk of HPV-6/11/16/18-related cervical intraepithelial neoplasia (CIN) 1-3 or adenocarcinoma in situ (AIS). Here, its impact on CIN1-3/AIS associated with nonvaccine oncogenic HPV types was evaluated. We enrolled 17,622 women aged 16-26 years. All underwent cervicovaginal sampling and Pap testing at regular intervals for up to 4 years. HPV genotyping was performed for biopsy samples, and histological diagnoses were determined by a pathology panel. Analyses were conducted among subjects who were negative for 14 HPV types on day 1. Prespecified analyses included infection of 6 months' duration and CIN1-3/AIS due to the 2 and 5 most common HPV types in cervical cancer after HPV types 16 and 18, as well as all tested nonvaccine types. Vaccination reduced the incidence of HPV-31/45 infection by 40.3% (95% confidence interval [CI], 13.9% to 59.0%) and of CIN1-3/AIS by 43.6% (95% CI, 12.9% to 64.1%), respectively. The reduction in HPV-31/33/45/52/58 infection and CIN1-3/AIS was 25.0% (95% CI, 5.0% to 40.9%) and 29.2% (95% CI, 8.3% to 45.5%), respectively. Efficacy for CIN2-3/AIS associated with the 10 nonvaccine HPV types was 32.5% (95% CI, 6.0% to 51.9%). Reductions were most notable for HPV-31. HPV-6/11/16/18 vaccine reduced the risk of CIN2-3/AIS associated with nonvaccine types responsible for approximately 20% of cervical cancers. The clinical benefit of cross-protection is not expected to be fully additive to the efficacy already observed against HPV-6/11/16/18-related disease, because women may have >1 CIN lesion, each associated with a different HPV type. ClinicalTrials.gov identifiers: NCT00092521 , NCT00092534 , and NCT00092482.
  The Journal of Infectious Diseases 03/2009; 199(7):926-35. · 6.41 Impact Factor
• Article: The impact of quadrivalent human papillomavirus (HPV; types 6, 11, 16, and 18) L1 virus-like particle vaccine on infection and disease due to oncogenic nonvaccine HPV types in sexually active women aged 16-26 years.

  Cosette M Wheeler, Susanne K Kjaer, Kristján Sigurdsson, Ole-Erik Iversen, Mauricio Hernandez-Avila, Gonzalo Perez, Darron R Brown, Laura A Koutsky, Eng Hseon Tay, Patricia García, [......], Frank J Taddeo, Christine Roberts, Amha Tadesse, Janine Bryan, Lisa C Lupinacci, Katherine E D Giacoletti, Margaret James, Scott Vuocolo, Teresa M Hesley, Eliav Barr
  [show abstract] [hide abstract]
  ABSTRACT: We evaluated the impact of a quadrivalent human papillomavirus (HPV) vaccine on infection and cervical disease related to 10 nonvaccine HPV types (31, 33, 35, 39, 45, 51, 52, 56, 58, and 59) associated with >20% of cervical cancers. The population evaluated included HPV-naive women and women with preexisting HPV infection and/or HPV-related disease at enrollment. Phase 3 efficacy studies enrolled 17,622 women aged 16-26 years. Subjects underwent cervicovaginal sampling and Pap testing on day 1 and then at 6-12-month intervals for up to 4 years. HPV typing was performed on samples from enrollment and follow-up visits, including samples obtained for diagnosis or treatment of HPV-related disease. All subjects who received 1 dose and returned for follow-up were included. Vaccination reduced the rate of HPV-31/33/45/52/58 infection by 17.7% (95% confidence interval [CI], 5.1% to 28.7%) and of cervical intraepithelial neoplasia (CIN) 1-3 or adenocarcinoma in situ (AIS) by 18.8% (95% CI, 7.4% to 28.9%). Vaccination also reduced the rate of HPV-31/58/59-related CIN1-3/AIS by 26.0% (95% CI, 6.7% to 41.4%), 28.1% (95% CI, 5.3% to 45.6%), and 37.6% (95% CI, 6.0% to 59.1%), respectively. Although a modest reduction in HPV-31/33/45/52/58-related CIN2 or worse was observed, the estimated reduction was not statistically significant. These cross-protection results complement the vaccine's prophylactic efficacy against disease associated with HPV-6, -11, -16, and -18. Long-term monitoring of vaccinated populations are needed to fully ascertain the population-based impact and public health significance of these findings. ClinicalTrials.gov identifiers: NCT00092521 , NCT00092534 , and NCT00092482.
  The Journal of Infectious Diseases 03/2009; 199(7):936-44. · 6.41 Impact Factor
• Article: Cervical length measurement and cervical phosphorylated insulin-like growth factor binding protein-1 testing in prediction of preterm birth in patients reporting uterine contractions.

  Leena Rahkonen, Leila Unkila-Kallio, Mika Nuutila, Susanna Sainio, Terhi Saisto, Eeva-Marja Rutanen, Jorma Paavonen
  [show abstract] [hide abstract]
  ABSTRACT: To evaluate the performance of cervical phosphorylated insulin-like growth factor binding protein-1 (phIGFBP-1) testing and cervical length measurement separately and in combination with physician's clinical judgment in prediction of preterm birth among patients with self-reported uterine contractions and intact membranes. We enrolled a total of 246 women between 22 and 34 weeks of gestation. The initial evaluation included cervical length measurement using transvaginal ultrasonography. Short cervix was defined as <25 mm. A swab sample was obtained from the cervix for phIGFBP-1. Admission was used as a clinical marker of an increased risk of preterm delivery <or=34 weeks. The diagnostic performances of the tests and clinician's judgment, as well as likelihood ratios (LRs) were calculated. Delivery <or=34 weeks and within 14 days. The overall rate of spontaneous preterm delivery <or=34 weeks was 4.1% (10/246). Short cervix, positive phIGFBP-1 test, combination of both, and clinician's judgment were all associated with preterm delivery <or=34 weeks or within 14 days (p<0.01). The negative predictive values for delivery <or=34 weeks were 97.4, 97.6, 97.1, and 98.7%, respectively, and within 14 days 98.7, 99.0, 98.3, and 99.6%, respectively. The corresponding positive LRs for delivery <or=34 weeks were 6.8, 3.8, 75.0, 14.9, and within 14 days 9.7, 5.5, 107.3, 17.1. The negative LRs were 0.6, 0.6, 0.7, 0.3 and 0.5, 0.3, 0.6, 0.2. The rapid phIGFBP-1-test has a high negative predictive value for preterm delivery, comparable to that of ultrasonographic cervical length measurement.
  Acta Obstetricia Et Gynecologica Scandinavica 02/2009; 88(8):901-8. · 1.77 Impact Factor
• Article: [Epidemiology and etiology of preterm delivery].

  Maija Jakobsson, Jorma Paavonen
  [show abstract] [hide abstract]
  ABSTRACT: The causes of the increase in preterm delivery are unknown. A large proportion of very early childbirths are due to infections, with a previous preterm delivery also constituting a strong risk factor. As much as 60% of preterm deliveries are, however, first births, whereby predicting is difficult. Important risk factors also include smoking, diseases of the mother and the fetus as well as the mother's age and social status. Prematurity is more common among blacks. Despite being previously considered safe, loop electrosurgery of the vaginal part of the cervix also predisposes to preterm delivery.
  Duodecim; lääketieteellinen aikakauskirja 02/2009; 125(12):1317-23.
• Source

  Available from: PubMed Central

  Article: A discrepancy of Chlamydia trachomatis incidence and prevalence trends in Finland 1983-2003.

  Erika Lyytikäinen, Marjo Kaasila, Eija Hiltunen-Back, Matti Lehtinen, Kaisa Tasanen, Heljä-Marja Surcel, Pentti Koskela, Jorma Paavonen
  [show abstract] [hide abstract]
  ABSTRACT: Reported rates of Chlamydia trachomatis are on the rise contradicting the declining rates of C. trachomatis associated reproductive sequelae in Western countries. Population based evaluation of the real trend of C. trachomatis infection is important to contemplate prevention efforts. We studied C. trachomatis occurrence during the past 20 years in Finland comparing incidence rate data based on serology and reported C. trachomatis laboratory notifications. A random sample of 7999 women with two consecutive pregnancies within five years was selected from the population of the Finnish Maternity Cohort (FMC) serum bank stratified by calendar year and age. C. trachomatis IgG antibodies were determined by a standard peptide-ELISA. The reported incidence rates of C. trachomatis infections based on case notifications were obtained from the National Registry of Infectious Diseases (NIDR). C. trachomatis seroprevalence rates decreased significantly from 1983 to 2003 both in women under 23 years of age (23.3% to 9.2%) and in women between 23-28-years of age (22.2% to 12.6%). However, seroconversion rates increased from 31 per 10000 person years in 1983-85 to 97 per 10000 person years in 2001-2003 (incidence rate ratio 3.2, 95% CI, 1.1-8.7) among the older age group. Seroconversion rate was highest (264) in 1983-1985 in the younger age-group, then declined and subsequently increased again (188) in 2001-2003. The incidence based on seroconversions was in agreement with the reported incidence rates in both age groups. C. trachomatis seroprevalence rate decreased during 1983-2003 among fertile-aged women in Finland. During the same time period incidence rates based both on seroconversions and reported laboratory notifications of diagnosed C. trachomatis infections increased. The discrepancy between the C. trachomatis incidence and seroprevalence trends warrants further studies.
  BMC Infectious Diseases 01/2009; 8:169. · 3.12 Impact Factor
• Source

  Available from: Elmar A Joura

  Article: HPV antibody levels and clinical efficacy following administration of a prophylactic quadrivalent HPV vaccine.

  Elmar A Joura, Susanne K Kjaer, Cosette M Wheeler, Kristján Sigurdsson, Ole-Erik Iversen, Mauricio Hernandez-Avila, Gonzalo Perez, Darron R Brown, Laura A Koutsky, Eng Hseon Tay, [......], Christine Roberts, Amha Tadesse, Janine Bryan, Lisa C Lupinacci, Katherine E D Giacoletti, Shuang Lu, Scott Vuocolo, Teresa M Hesley, Richard M Haupt, Eliav Barr
  [show abstract] [hide abstract]
  ABSTRACT: The efficacy of the quadrivalent Human Papillomavirus (HPV) vaccine is thought to be mediated by humoral immunity. We evaluated the correlation between quadrivalent HPV vaccine-induced serum anti-HPV responses and efficacy. 17,622 women were vaccinated at day 1, and months 2 and 6. At day 1 and at 6-12 months intervals for up to 48 months, subjects underwent Papanicolaou and genital HPV testing. No immune correlate of protection could be found due to low number of cases. Although 40% of vaccine subjects were anti-HPV 18 seronegative at end-of-study, efficacy against HPV 18-related disease remained high (98.4%; 95% CI: 90.5-100.0) despite high attack rates in the placebo group. These results suggest vaccine-induced protection via immune memory, or lower than detectable HPV 18 antibody titers.
  Vaccine 11/2008; 26(52):6844-51. · 3.77 Impact Factor