| 1. |
- Dahlström, Lisen Arnheim, et al.
(author)
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Prospective seroepidemiologic study of human papillomavirus and other risk factors in cervical cancer
- 2011
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In: Cancer Epidemiology, Biomarkers and Prevention. - 1055-9965 .- 1538-7755. ; 20:12, s. 2541-2550
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Journal article (peer-reviewed)abstract
- Background: Several sexually transmitted infections (STI) have been reported to interact with human papillomavirus (HPV) in the etiology of cervical cancer. A large cohort study is required to obtain a both unbiased and stable estimate of their effects. Methods: Four major biobanks in the Nordic Countries containing samples from about 1,000,000 subjects were linked with nation-wide cancer registries. Serum samples from 604 women with invasive cervical cancer (ICC) diagnosed on average 10 years after sampling and 2,980 matched control women were retrieved and analyzed with serology for key STI. Results: Exposure to HPV16 was the strongest risk factor for cervical cancer [ OR = 2.4; 95% confidence interval (CI), 2.0-3.0], particularly for squamous cell carcinoma (OR = 2.9; 95% CI, 2.2-3.7). HPV18 was strongly associated with increased risk for adenocarcinoma (OR = 2.3; 95% CI, 1.3-4.1). Baseline seropositivity for HPV16 did not confer any increased risk for HPV18 DNA-positive cancer and conversely HPV18 seropositivity had no association with HPV16 DNA-positive cancers. HPV6 had no effect on its own (OR = 1.1; 95% CI, 0.9-1.3), but had an antagonistic effect on the risk conferred by HPV16 (P < 0.01). Herpes simplex virus 2 had little or no association (OR = 1.1; 95% CI, 0.8-1.4). Previous exposure to Chlamydia trachomatis, as indicated by serum antibodies, had a strongly increased risk for cervical cancer (OR = 1.9; 95% CI, 1.5-2.3). Conclusions: A large prospective study has assessed the role of different STIs in cervical cancer. Impact: Prospective evidence supports cofactor role of some STI in cervical cancer. Cancer Epidemiol Biomarkers Prev; 20(12); 2541-50. (C) 2011 AACR.
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| 2. |
- Dillner, Joakim, et al.
(author)
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Long term predictive values of cytology and human papillomavirus testing in cervical cancer screening: joint European cohort study.
- 2008
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In: BMJ: British Medical Journal. - : BMJ. - 1756-1833 .- 0959-8138 .- 1468-5833. ; 337
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Journal article (peer-reviewed)abstract
- OBJECTIVE: To obtain large scale and generalisable data on the long term predictive value of cytology and human papillomavirus (HPV) testing for development of cervical intraepithelial neoplasia grade 3 or cancer (CIN3+). DESIGN: Multinational cohort study with joint database analysis. SETTING: Seven primary HPV screening studies in six European countries. PARTICIPANTS: 24,295 women attending cervical screening enrolled into HPV screening trials who had at least one cervical cytology or histopathology examination during follow-up. MAIN OUTCOME MEASURE: Long term cumulative incidence of CIN3+. RESULTS: The cumulative incidence rate of CIN3+ after six years was considerably lower among women negative for HPV at baseline (0.27%, 95% confidence interval 0.12% to 0.45%) than among women with negative results on cytology (0.97%, 0.53% to 1.34%)). By comparison, the cumulative incidence rate for women with negative cytology results at the most commonly recommended screening interval in Europe (three years) was 0.51% (0.23% to 0.77%). The cumulative incidence rate among women with negative cytology results who were positive for HPV increased continuously over time, reaching 10% at six years, whereas the rate among women with positive cytology results who were negative for HPV remained below 3%. CONCLUSIONS: A consistently low six year cumulative incidence rate of CIN3+ among women negative for HPV suggests that cervical screening strategies in which women are screened for HPV every six years are safe and effective.
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| 3. |
- Forslund, Ola, et al.
(author)
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Population-based type-specific prevalence of high-risk human papillomavirus infection in middle-aged Swedish Women.
- 2002
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In: Journal of Medical Virology. - : Wiley. - 1096-9071 .- 0146-6615. ; 66:4, s. 535-541
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Journal article (peer-reviewed)abstract
- Human papillomavirus (HPV) DNA testing can be used to identify women at risk of the development of cervical cancer. The cost-effectiveness of HPV screening is dependent on the type-specific HPV prevalence in the general population. The present study describes the prevalence and spectrum of high-risk HPV types found in a large real-life population-based HPV screening trial undertaken entirely within the cervical screening program offered to middle-aged Swedish women. Cervical brush samples from 6,123 women aged 32-38 years were analyzed using a general HPV primer (GP5(+)/6(+)) polymerase chain reaction-enzyme immunoassay (PCR-EIA) combined with reverse dot-blot hybridization for confirmation and HPV typing by a single assay. In this study, 6.8% (95% CI 6.2-7.5) (417/6,123) were confirmed as high-risk HPV positive. Infections with 13 different high-risk HPV types were detected, of which HPV 16 was the most prevalent type (2.1%; 128/6,123), followed by HPV 31 (1.1%; 67/6,123). Any one of the HPV types 18, 33, 35, 39, 45, 51, 52, 56, 58, 59, or 66 was detected in 3.6% (223/6,123) of the women. Infection with two, three, and five types simultaneously was identified in 32, 5, and 1 women, respectively. The combination of PCR-EIA as a screening test and reverse dot-blot hybridization as a confirmatory test, was found to be readily applicable to a real-life population-based cervical screening. The type-specific HPV prevalence found support in previous modeling studies suggesting that HPV screening may be a favorable cervical screening strategy.
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| 4. |
- Holl, Katsiaryna, et al.
(author)
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Endogenous steroid hormone levels in early pregnancy and risk of testicular cancer in the offspring: A nested case-referent study
- 2009
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In: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 124:12, s. 2923-2928
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Journal article (peer-reviewed)abstract
- According to the leading hypothesis on testicular cancer (TC) etiology exposure to a specific pattern of steroid hormones in utero, in particular, to high levels of estrogens and low levels of androgens is the major determinant of TC risk in the offspring. We performed a case-referent study nested within Finnish, Swedish and Icelandic maternity cohorts exploiting early pregnancy serum samples to evaluate the role of maternal endogenous steroid hormones with regard to the risk of TC. TC cases and referents were aged between 0 and 25 years. For each case-index mother pair, three or four matched referent-referent mother pairs Were identified using national population registries. First trimester or early second trimester sera were retrieved from the index mothers of 73 TC cases and 286 matched referent mothers, and were tested for dehydroepiandrosterone sulfate (DHEAS), androstenedione, testosterone, estradiol, estrone, and sex hormone binding globulin (SHBG,). Offspring of mothers with high DHEAS levels had a significantly decreased risk of TC (OR for highest vs. lowest DHEAS quartile, 0.18 (95% CI 0.06-0.58). In contrast, offspring of mothers With high androstenedione levels had ail increased risk of TC (OR 4.1; 95% CI 1.2-12.0). High maternal total estradiol level also tended to be associated with an increased risk of TC in the offspring (OR 32; 95% CI 0.98-1,090). We report the first direct evidence that interplay or maternal steroid hormones in the early pregnancy is important in the etiology of TC in the offspring. (C) 2009 UICC
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| 5. |
- Holl, Katsiaryna, et al.
(author)
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Maternal Epstein-Barr virus and cytomegalovirus infections and risk of testicular cancer in the offspring: a nested case-control study
- 2008
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In: APMIS : acta pathologica, microbiologica, et immunologica Scandinavica. - Oxford : Wiley. - 1600-0463 .- 0903-4641. ; 116:9, s. 816-822
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Journal article (peer-reviewed)abstract
- During recent decades the incidence of testicular cancer (TC) has increased rapidly around the world. Associated exogenous etiological factors might therefore be identifiable. We performed a case-control study nested within Finnish, Swedish and Icelandic maternity cohorts exploiting early pregnancy serum samples to evaluate the role of congenital or neonatal infections with Epstein-Barr virus (EBV) and cytomegalovirus (CMV) as risk factors of TC in the offspring. For each case-index mother pair, three or four matched control-control mother pairs were identified using national population registries. First trimester sera were retrieved from the index mothers of 66 TC cases and 258 matched control mothers and were tested for antibodies to EBV and CMV. High level of maternal EBV IgG antibodies was associated with significantly increased risk of TC in the offspring (odds ratio (OR) 2.50; 95% confidence interval (CI) 1.15, 5.40), especially with risk of non-seminoma TC (OR, 2.73: 95% CI, 1.25, 5.99) and non-seminoma TC diagnosed under 8 years of age(OR, 2.72; 95% CI, 1.05, 7.04). In contrast, offspring of CMV IgG-seropositive mothers had a decreased risk of TC diagnosed under 8 years of age (OR, 0.35; 95% CI, 0.14, 0.89). Our results suggest that EBV and CMV infections may be associated with TC.
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| 6. |
- Kapeu, Aline Simen, et al.
(author)
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Is Smoking an Independent Risk Factor for Invasive Cervical Cancer? A Nested Case-Control Study Within Nordic Biobanks
- 2009
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In: American Journal of Epidemiology. - Baltimore, Md. : Oxford University Press (OUP). - 0002-9262 .- 1476-6256. ; 169:4, s. 480-488
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Journal article (peer-reviewed)abstract
- The strong correlation between smoking and exposure to oncogenic human papillomaviruses (HPVs) has made it difficult to verify the independent role of smoking in cervical carcinogenesis. Thus, the authors evaluated this role. Five large Nordic serum banks containing samples from more than 1,000,000 subjects were linked with nationwide cancer registries (1973-2003). Serum samples were retrieved from 588 women who developed invasive cervical cancer and 2,861 matched controls. The samples were analyzed for cotinine (a biomarker of tobacco exposure) and antibodies to HPV types 16 and 18, herpes simplex virus type 2, and Chlamydia trachomatis. Smoking was associated with the risk of squamous cell carcinoma (SCC) among HPV16- and/or HPV18-seropositive heavy smokers (odds ratio = 2.7, 95% confidence interval: 1.7, 4.3). A similar risk of SCC (odds ratio = 3.2, 95% confidence interval: 2.6, 4.0) was found in heavy smokers after adjustment for HPV16/18 antibodies. The point estimates increased with increasing age at diagnosis and increasing cotinine level. This study confirms that smoking is an independent risk factor for cervical cancer/SCC in women infected with oncogenic HPVs. These findings emphasize the importance of cervical cancer prevention among women exposed to tobacco smoke.
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| 7. |
- Naucler, Pontus, et al.
(author)
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Efficacy of HPV DNA testing with cytology triage and/or repeat HPV DNA testing in primary cervical cancer screening.
- 2009
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In: Journal of the National Cancer Institute. - : Oxford University Press (OUP). - 1460-2105 .- 0027-8874. ; 101:2, s. 88-99
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Journal article (peer-reviewed)abstract
- Primary cervical screening with both human papillomavirus (HPV) DNA testing and cytological examination of cervical cells with a Pap test (cytology) has been evaluated in randomized clinical trials. Because the vast majority of women with positive cytology are also HPV DNA positive, screening strategies that use HPV DNA testing as the primary screening test may be more effective.
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| 8. |
- Naucler, Pontus, et al.
(author)
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HPV type-specific risks of high-grade CIN during 4 years of follow-up : A population-based prospective study
- 2007
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In: British Journal of Cancer. - : Springer Science and Business Media LLC. - 0007-0920 .- 1532-1827. ; 97:1, s. 129-132
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Journal article (peer-reviewed)abstract
- We followed a population-based cohort of 5696 women, 32 - 38 years of age, by registry linkage with cytology and pathology registries during a mean follow-up time of 4.1 years to assess the importance for CIN2 + development of type-specific HPV DNA positivity at baseline. HPV 16, 31 and 33 conveyed the highest risks and were responsible for 33.1, 18.3 and 7.7% of CIN2 + cases, respectively. Women infected with HPV 18, 35, 39, 45, 51, 52, 56, 58, 59 and 66 had significantly lower risks of CIN2 + than women infected with HPV 16. After adjustment for infection with other HPV types, HPV types 35, 45, 59 and 66 had no detectable association with CIN2 +. In summary, the different HPV types found in cervical cancer show distinctly different CIN2 + risks, with high risks being restricted to HPV 16 and its close relatives HPV 31 and HPV 33.
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| 9. |
- Naucler, Pontus, et al.
(author)
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Human papillomavirus and Papanicolaou tests to screen for cervical cancer.
- 2007
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In: New England Journal of Medicine. - Boston, Massachusetts : Massachusetts medical society. - 0028-4793 .- 1533-4406. ; 357:16, s. 1589-97
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Journal article (peer-reviewed)abstract
- Background Screening for cervical cancer based on testing for human papillomavirus (HPV) increases the sensitivity of detection of high-grade (grade 2 or 3) cervical intraepithelial neoplasia, but whether this gain represents overdiagnosis or protection against future high-grade cervical epithelial neoplasia or cervical cancer is unknown. Methods In a population-based screening program in Sweden, 12,527 women 32 to 38 years of age were randomly assigned at a 1:1 ratio to have an HPV test plus a Papanicolaou (Pap) test (intervention group) or a Pap test alone (control group). Women with a positive HPV test and a normal Pap test result were offered a second HPV test at least 1 year later, and those who were found to be persistently infected with the same high-risk type of HPV were then offered colposcopy with cervical biopsy. A similar number of double-blinded Pap smears and colposcopies with biopsy were performed in randomly selected women in the control group. Comprehensive registry data were used to follow the women for a mean of 4.1 years. The relative rates of grade 2 or 3 cervical intraepithelial neoplasia or cancer detected at enrollment and at subsequent screening examinations were calculated. Results At enrollment, the proportion of women in the intervention group who were found to have lesions of grade 2 or 3 cervical intraepithelial neoplasia or cancer was 51% greater (95% confidence interval [CI], 13 to 102) than the proportion of women in the control group who were found to have such lesions. At subsequent screening examinations, the proportion of women in the intervention group who were found to have grade 2 or 3 lesions or cancer was 42% less (95% CI, 4 to 64) and the proportion with grade 3 lesions or cancer was 47% less (95% CI, 2 to 71) than the proportions of control women who were found to have such lesions. Women with persistent HPV infection remained at high risk for grade 2 or 3 lesions or cancer after referral for colposcopy. Conclusions The addition of an HPV test to the Pap test to screen women in their mid-30s for cervical cancer reduces the incidence of grade 2 or 3 cervical intraepithelial neoplasia or cancer detected by subsequent screening examinations.
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| 10. |
- Pukkala, Eero, et al.
(author)
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Nordic biological specimen banks as basis for studies of cancer causes and control - more than 2 million sample donors, 25 million person years and 100 000 prospective cancers
- 2007
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In: Acta Oncologica. - : Informa UK Limited. - 1651-226X .- 0284-186X. ; 46:3, s. 286-307
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Journal article (peer-reviewed)abstract
- The Nordic countries have a long tradition of large-scale biobanking and comprehensive, population-based health data registries linkable on unique personal identifiers, enabling follow-up studies spanning many decades. Joint Nordic biobank-based studies provide unique opportunities for longitudinal molecular epidemiological research. The purpose of the present paper is to describe the possibilities for such joint studies, by describing some of the major Nordic biobank cohorts with a standardised calculation of the cancer incidence in these cohorts. Altogether two million donors have since 1966 donated more than four million biological samples, stored at -20 degrees C to -135 degrees C, to 17 biobank cohorts in Finland, Iceland, Norway and Sweden. As a result of joint database handling principles, the accuracy of personal identifiers and completeness of follow-up for vital status in all participating biobanks was improved. Thereafter, the cancer incidence was determined using follow-up through the national cancer registries. Biobanks based on random samples of population typically showed slightly lower cancer incidence rates than the general population, presumably due to better participation rates among health-conscious subjects. On the other hand, biobanks including samples for viral screening or clinical testing showed 1.5 to 2.1 fold increased incidence of cancer. This excess was very high immediately after sampling, but for some cancer sites remained elevated for years after clinical sampling. So far, more than 100 000 malignant neoplasms have occurred after sample donation, and the annual increase of the cancer cases in these cohorts is about 10 000. The estimates on the population-representativity of the biobanks will assist in interpretation of generalizability of results of future studies based on these samples, and the systematic tabulations of numbers of cancer cases will serve in study power estimations. The present paper summarizes optimal study designs of biobank-based studies of cancer.
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