Data Material (Cohorts and Case Control Studies)

The HPV Cohort
The LBC Cohort
The LIVA, FREJA and HERKULES Cohorts
The KOKO Cohort
The Soldier Cohorts 
MALOVA 
OCAC
The Borderline Tumour Cohort
The Danish Infertility Cohort

The HPV Cohort

The original purpose of the HPV Cohort was to investigate the connection between human papilloma virus (HPV) and cervical neoplasia. The HPV Cohort was initiated in the period 1991-93. The cohort consists of 11,088 women aged 20-29 years, all of them residing within the area covered by Rigshospitalet at the commencement of the study.

The study included an interview, where the women answered questions relating to socio-demographic factors, lifestyle habits, sexual habits, reproductive factors etc. Furthermore, the women had a gynaecological examination. All women were invited to follow-up examinations 2, 8 and/or 10 years after the initial inclusion into the study.

The LBC Cohort

Relatively few years ago, a new technique was introduced to screen for cervical cancer, where the conventional cytology was replaced by the fluid-based cytology, in which the cell sample, collected for cytological examination, is stored in a fluid, which subsequently can be tested for different infections, such as Chlamydia and HPV. A monolayer smear from the fluid-based cell sample is performed at the clinic, and the rest of the sample is stored at the pathology department until a final cytological diagnosis has been made. Afterwards, the remaining sample is disposed of.

I relation to our LBC-study, the remaining material, which is normally thrown out, has been collected. We collected from 2002 till 2005 (consecutively on random days) liquid-based cervix cytology samples from 40,399 women via the Pathology Department at Hvidovre Hospital. The department receives and analyses all cervix cytological samples (and histology) from the entire greater Copenhagen area, related to organised and opportunistic screening both. In case of a subsequent biopsy/cone section this tissue is also sent to the Pathology Department at Hvidovre Hospital. All samples have been tested for HPV (HC2 high-risk HPV types and low-risk HPV types) and an HPV type determination has been made by LiPA (PCR- method).

Follow-up
The established cohort is passively followed by the Pathology Data Bank in order to identify any cell changes and subsequent treatments related to the index cytology. The cohort will be coupled with the Pathology Data Bank at regular intervals to gain information on all subsequent cervix cytological and histological examinations. In addition, information will be obtained about previous cervical abnormalities in the cohort through the Pathology Data Bank. The cohort has also been coupled to the National Patient Registry, where we have requested information on all admissions since 1977.

The LIVA, FREJA and HERKULES Cohorts

Within the unit we have conducted three major questionnaire surveys: LIVA and FREJA among Danish women, and HERKULES among Danish men. Overall, the purpose of the surveys was a collection of data concerning different lifestyle factors, and more specifically to collect data on genital warts and knowledge of HPV. This knowledge will be important in connection with the introduction of a vaccine against HPV and cervical cancer.

The LIVA survey was initiated in November 2004 and concluded in June 2005. In total, 28,000 randomly selected women aged 18-45 years from the entire country were invited to participate. The participants were randomly chosen from the Central Person Register, where we have information on date of birth and geography for all potential participants. In total, we succeeded in including more than 22,000 women into the study (participation > 81%). All participants have answered questions on the following subjects:

Socio-demographic variables, self estimated health and physique, height, weight, use of pain-alleviating medicine, smoking, alcohol consumption, pregnancies, sexually transmitted diseases with special emphasis on genital warts, knowledge about HPV, and screening for cervical cancer.

The LIVA survey is part of a Nordic collaborative project with information about approximately 70,000 Nordic females (all Nordic countries with the exception of Finland). The LIVA women have once been coupled to the Pathology Data Bank for information on cervix cytological examinations.

The FREJA survey is identical to the LIVA survey with regard to study design and types of questions. FREJA started in November 2011 and was concluded in June 2012. In all, 26,000 women 18 to 45 years of age were invited and approximately 18,700 participated in the survey.

The HERKULES survey was initiated in November 2006 and concluded in June 2007. In total more than 23,000 men participated in the survey, a participation rate of 71%. The men answered more or less the same questions as the women in the LIVA survey.

The KOKO Cohort

The KOKO project is a prospective follow-up study; initiated September 2002 (total study period is 5 years). The study includes approx. 700 Danish women, included in the study due to a diagnosis of high-grade cervical dysplasia, followed by loop conization. Participation in the project entails 2 control visits at 4-6 and 8-12 months after the procedure, respectively, performing HPV tests, cell sample from the cervix, colposcopy, and a minor questionnaire on risk factors for HPV infection. An HPV test was performed prior to the cone section, as well as a short questionnaire. The study was performed at gynaecological and obstetrical departments at Frederiksberg, Hvidovre, Roskilde, and Skejby hospitals.

The Soldier Cohorts

The Soldier Follow-up Cohort
The purpose of the study was to examine the natural history of genital HPV infection in men. The study had 2 rounds of examination: A recruitment phase (Fall 1998) and a follow-up phase (Spring 1999). In total, 388 men were included and 322 re-examined. Age interval: 18-29 (93% between19-22).

In both examination rounds all participants gave samples for determination of HPV (swab) and Chlamydia (urine sample). In addition, a blood sample for later analysis of HPV antibodies. Finally, the participants completed a questionnaire on among other things sexual behaviour.

The Soldier Cohort
The purpose of this study of soldiers was to determine the prevalence of HPV overall, with respect to high-risk and low-risk types, individual types such as HPV 16 and 18, and to examine risk factors for genital infection with HPV. To obtain as precise measurements as possible for this, a significantly larger number of participants were included compared to the previous study and with a wider age distribution.

The study took place during 2006, and in total more than 2,500 men aged 18 to 55 were included. The participants were sampled for HPV determination (swab). In addition, they completed a questionnaire about lifestyle factors and sexual behaviour.

MALOVA

The overall purpose is identification of possible risk factors for the development of ovarian tumours, including malignant, borderline, and benign tumours, and to examine possible prognostic factors for the survival of ovarian cancer.

The Malova (MALignant OVArian Cancer) study is a case-control study. Cases are women (35-79 years) from Zealand (excluding Holbæk), Funen, Southern Jutland, and Northern Jutland who underwent surgery for ovarian tumours in the period December 1994 till May 1999. I total, 698 women with ovarian cancer, 219 women with borderline tumours, and 450 women with benign tumours were included. A control group consisting of two women per case - matched by geographical area and age - were drawn from the CPR. A total of 2,130 controls participated.

All women were interviewed about different lifestyle factors, such as socio-demographic factors, reproductive anamnesis, contraception, diet and smoking habits, physical activity, earlier health anamnesis, and familiar disposition. In addition, the women submitted a blood sample that subsequently has been analysed for among others, CA125, tetranectin, gonadotropins, inhibin A, and steroid hormones. For cases, the surgery descriptions from the patient charts were reviewed independently by two gynaecological specialists in ovarian cancer for the purpose of determination of FIGO stage. Pathology results and tissue samples were collected and reviewed blinded by a pathologist, specialised in gynaecological tumours.

OCAC

Data from the MALOVA study enters into a large international consortium: the Ovarian Cancer Association Consortium (OCAC).

OCAC is an international, multidisciplinary consortium formed in 2005, consisting of more than 50 case-control and case-only studies of ovarian cancer. Each study has submitted demographic, clinical, and epidemiological data to a central database. The main purpose of OCAC is to identify genes that may be related to the risk of developing ovarian cancer. By combining data from the many studies entered into OCAC, a more reliable assessment of the risks associated with the identified genes may be obtained, compared to an analysis of a smaller data material. Data from OCAC are also used to study risk factors for ovarian cancer and to identify prognostic factors for ovarian cancer survival.

Finally, data from OCAC are used to identify a woman's individual risk of developing ovarian cancer. This is done by quantifying the relative significance of genetic and environment/lifestyle related risk factors, respectively, with respect to the risk of ovarian cancer (i.e. gene-environment interaction analyses).

For more information, see the OCAC webpage

The Borderline Tumour Cohort

The SBT Cohort (serous borderline tumours) was established in 2002. It consists of approx. 1,000 Danish women, registered with a diagnosis of a serous borderline tumour in the ovaries from 1978 till 2002 in the Pathology Data Bank and/or the Cancer Registry. The histological samples from all women were examined by a panel of pathological experts from Denmark (Hvidovre University Hospital), verifying the diagnosis, and their charts were also collected. The purpose is assessment of incidence, prognosis, and risk of recurrence and progression to ovarian cancer. Furthermore, the purpose is to identify potential molecular biological markers for serous borderline tumours in the ovaries.

The Danish Infertility Cohort

The Danish Infertility Cohort was established in 1997, and consisted originally of 54,362 Danish women referred to examination for infertility in the period 1963-1998. The women in the cohort were identified either directly from the hospital departments and private clinics, involved in diagnosing and treating fertility problems in the aforementioned period, or extracted from the National Patient Registry, incorporating all women registered with an infertility diagnosis. For a smaller group of women, chart information about causes of infertility and exposure to hormonal infertility treatment were obtained.

In recent years, the Danish Inferitlity Cohort has been updated with information from the National Patient Registry, the IVF-Registry, and the National Prescription Registry, and now contains information on approximately 180,000 women with fertility problems in Denmark in the period 1963-1998. In addition, all children born to women with fertility problems have also been identified through the Medical Birth Registry and the CPR register, totalling approximately 240,000 children in the period 1968-2012.

The main purpose for the establishment of the cohort was examination of the connection between fertility problems, fertility treatment, and the risk of different types of hormone associated cancers. Data from the cohort is, however, also used for the examination of connections between infertility and other morbidity among the affected women, and the risk of cancer and other morbidity among children born by women with fertility problems. The Danish Infertility Cohort is continuously coupled to the Danish health registries in order to follow the development of disease incidence among the affected women and their children.