[Show abstract][Hide abstract] ABSTRACT: The AS04-adjuvanted bivalent L1 virus-like-particle (VLP) vaccine (CervarixTM) 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.
[Show abstract][Hide abstract] 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; · 5.85 Impact Factor
[Show abstract][Hide abstract] 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; · 3.20 Impact Factor
[Show abstract][Hide abstract] 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; · 1.71 Impact Factor
[Show abstract][Hide abstract] 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 01/2014; 15(3):1497-1500. · 1.50 Impact Factor
[Show abstract][Hide abstract] 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 12/2013; · 6.20 Impact Factor
[Show abstract][Hide abstract] 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. · 2.08 Impact Factor
[Show abstract][Hide abstract] 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. · 5.85 Impact Factor
[Show abstract][Hide abstract] 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; · 1.81 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Human papillomavirus (HPV) is the most common sexually transmitted infectious agent; its 14 oncogenic types are causally associated with 5-10% of all cancers. The major structural HPV protein self-assembles into immunogenic virus-like particles. Two licensed HPV vaccines-the bivalent vaccine comprising HPV types 16 and 18, and the quadrivalent vaccine comprising HPV types 6, 11, 16 and 18-have proven to be safe and efficacious against 6-month-persistent cervical infections of HPV16 and HPV18 and associated precancerous lesions, and both have efficacies of 90-100%. Among baseline HPV-negative adolescent females, vaccine efficacies against the immediate precursor of cervical cancer (intraepithelial neoplasia grade 3) irrespective of HPV type are 93.2% and 43.0% for the bivalent and quadrivalent vaccines, respectively. The quadrivalent vaccine is efficacious (>75% vaccine efficacy) against any of the more-severe precursors of vulval, vaginal and anal cancers. A strong increase in vaccine efficacy with increasing severity of the precancerous lesion is explained by accumulation of the most-oncogenic HPV types 16 and 18 in these lesions. Therefore, prophylactic HPV vaccination will exceed the best results from screening for cancer. With the extremely efficacious prophylactic HPV vaccines, the focus of organized intervention (vaccination and screening) programmes should, however, shift from reducing the HPV disease burden to controlling the prevalence of oncogenic HPV (and nononcogenic HPV) types. Eradication of the major oncogenic HPV types should be pursued.
[Show abstract][Hide abstract] 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 measured in paired sera of the cases and 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.
International Journal of Cancer 01/2013; 133(7). · 6.20 Impact Factor
[Show abstract][Hide abstract] 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 01/2013; 8(8):e72088. · 3.53 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: In recent decades, increasing rates of Chlamydia cases have contrasted with decreasing Chlamydia trachomatis seroprevalence rates and decreasing Chlamydia-associated complication rates. We elucidated the conflicting trends by studying incidence of repeated Chlamydia infections over time.
Chlamydia cases reported during 1995 to 2009 were identified in the Finnish National Infectious Diseases Registry. Trends of single and repeated diagnoses of Chlamydia infection were analyzed.
Our study population comprised 147,148 individuals with a total of 177,138 genital chlamydial infections. The proportion of annual repeated diagnoses of genital infections increased among female and males from 4.9% to 7.3% and from 3.8% to 5.3%, respectively. In 2009, 24.8% of the females and 20.3% of the males had had an earlier Chlamydia infection ever during the follow-up time. Of all the repeated diagnoses, 34.1% occurred within 12 months. The highest rates of repeated infection diagnoses occurred in 25-year-old women (37.0%) and in 29-year-old men (30.9%) in a cohort of individuals born in 1979.
A gradual increase of repeated Chlamydia infections resulted in 43% increase in annual infections between 1996 and 2009. The result is supportive of the existing seroprevalence data suggesting that Chlamydia infection burden is not increasing in the whole population. The increasing infection rates in males, in particular, justify development of effective strategy in preventing reinfections and onward transmission.
[Show abstract][Hide abstract] ABSTRACT: Background. We assessed if risk of developing cervical intraepithelial neoplasia grade 2/3 (CIN2-3) or adenocarcinoma in situ (AIS) is associated with a short interval between menarche and first sexual intercourse (FSI).Methods. 1009 Colombian and 1012 Finnish non-virgins aged 16-23 enrolled in the phase 3 trials of a quadrivalent HPV-6/11/16/18 vaccine had non-missing data for age of menarche and first sexual intercourse. The impact of menarche interval on the odds of developing CIN2-3/AIS was evaluated in placebo recipients who were DNA-negative to HPV6/11/16/18/31/33/35/39/45/51/52/56/58/59 and seronegative to HPV 6/11/16/18 at Day 1, and had a normal Pap result at Day 1 and Month 7, thus approximating sexually-naïve adolescents (n=504).Results. The mean age of menarche and FSI was 12.4 and 16.0 years, respectively. Among the women approximating sexually-naïve adolescents, 18 developed CIN2-3/AIS. Compared with women who postponed first intercourse beyond 3 years, those with first intercourse within 3 years of menarche had a greater risk of cytologic abnormalities (OR=1.65, 95%CI: 1.02─2.68; p=0.04) and CIN2-3/AIS (OR=3.56, 95%CI: 1.02─12.47; p=0.05).Conclusions. A short interval between menarche and FSI was a risk factor for cytologic abnormalities and high-grade cervical disease. These data emphasize the importance of primary prevention through education and vaccination.
The Journal of Infectious Diseases 10/2012; · 5.85 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Prophylactic human papillomavirus vaccine efficacy is almost too good to be true. The benefits of herd immunity will, however, not be gained without high vaccine coverage. Here the authors of two recent papers on HPV16/18 vaccine efficacy elaborate on the basics and implications of this approach for infection and cancer prevention.
[Show abstract][Hide abstract] ABSTRACT: OBJECTIVE: We evaluated baseline data from the PApilloma TRIal against Cancer In young Adults (PATRICIA; NCT00122681) on the association between behavioral risk factors and HPV infection and cervical abnormalities. METHODS: Women completed behavioral questionnaires at baseline. Prevalence of HPV infection and cervical abnormalities (detected by cytological or histological procedures) and association with behavioral risk factors were analyzed by univariate and stepwise multivariable logistic regressions. RESULTS: 16782 women completed questionnaires. Among 16748 women with data for HPV infection, 4059 (24.2%) were infected with any HPV type. Among 16757 women with data for cytological abnormalities, 1626 (9.7%) had a cytological abnormality, of whom 1170 (72.0%) were infected with at least one oncogenic HPV type including HPV-16 (22.7%) and HPV-18 (9.3%). Multivariable analysis (adjusted for age and region, N=14404) showed a significant association between infection with any HPV type and not living with a partner, smoking, age <15years at first sexual intercourse, higher number of sexual partners during the past 12months, longer duration of hormonal contraception and history of sexually transmitted infection (STI). For cervical abnormalities, only history of STI (excluding Chlamydia trachomatis) remained significant in the multivariable analysis after adjusting for HPV infection. CONCLUSIONS: Women reporting 3+ sexual partners in the past 12months had the highest risk of HPV infection at baseline. HPV infection was the main risk factor for cervical abnormalities, and history of STIs excluding Chlamydia trachomatis increased risk to a lesser extent. Although behavioral factors can influence risk, all sexually active women are susceptible to HPV infection.