Kristjan Sigurdsson

The Icelandic and Nordic cervical screening programs, Trends in incidence and mortality rates through 1995

BACKGROUNDnThe objective of cervical cancer screening is to lower the incidence and mortality rates of the disease. This study evaluates the effectiveness of cervical screening and the UICC and EC screening recommendations based on the Nordic screening experience.nnnMETHODSnThe study analyzes the features of the Icelandic and the Nordic screening programs and the observed trends in the incidence and mortality rates in these countries through 1995.nnnRESULTSnOrganized screening started in all the Nordic countries soon after 1960 and had nation-wide coverage in all these countries, except in Denmark (45% coverage in 1991), by around 1973 but in Norway screening was only spontaneous up to late in 1994. Up to 1985 the target age group and screening interval were most intensive in Iceland, followed by Finland, Sweden and Denmark. All countries except Finland lowered the lower age limit and intensified the screening intervals after 1985. Through the period 1986-1995 the reduction in both the mortality and the incidence rates was greatest in Iceland (mortality: 76% and incidence: 67%) and Finland (73% and 75%, respectively), intermediate in Sweden (60% and 55%, respectively) and Denmark (55% and 54%, respectively), and lowest in Norway (43% and 34%, respectively). The age-specific incidence in the 20-29 age group has been increasing since 1971 in all the Nordic countries, except in Finland, where the yearly registered age-specific incidence has been increasing in the targeted 30-54 age group since 1991. In Iceland screening has greatly affected the rate of all stages of squamous cell carcinoma, but not the rate of adeno- and adenosquamous carcinomas. In fact the rate of adenocarcinoma has been increasing.nnnCONCLUSIONSnOrganized screening is more effective than spontaneous screening in reducing the risk of cervical cancer. Although differences in environmental, biological and ethnic factors may call for different screening strategies, screening should preferably start soon after age 20 with a screening interval of 2-3 years.

Prognostic factors in malignant epithelial ovarian tumors

In a study of 494 patients with ovarian carcinoma all known factors that eventually influence prognosis were tested both separately and comparatively in a multivariate statistical analysis, using survival as the dependent variable. It was found that the histologic grade and the size of the residual tumor after surgery are the most important factors influencing survival. The histologic type affected prognosis only in Stage III patients with large residual tumors. The stage of tumor progression had prognostic value, although Stage IIa was found to have the same survival rate as Stage I of this disease. The state of the tumor capsules in Stage I had no prognostic effect. Ascites only affected survival in Stage III patients who had small or no residual tumor after surgery. Age was found to influence survival only in Stage III patients with small residual tumors, or no residual tumor, and in advanced Stage II cases. Continued chemotherapy seems to be of benefit in Stage III patients with small or no residual tumors following surgery.

HPV genotypes in CIN 2-3 lesions and cervical cancer : A population-based study

The distribution of human papillomavirus (HPV) varies between countries and continents leading to different effectiveness of upcoming prophylactic HPV vaccines. This study analyses the HPV distribution in CIN 2‐3, recurrent CIN 2‐3 and cervical cancer in Iceland. About 80% of incident cases with CIN 2‐3 lesions in 1990 and 1999, 99% of cancer cases in 1990–1994 and 1999–2003, and cases with recurrent CIN 2‐3 after conization in 1990 were tested with PCR analysis for the presence of 12 oncogenic HPV types. About 95% of the CIN 2‐3 and 92% of the cancer cases tested positive for the included HPV types. HPV 16 was the most frequent type followed by HPV 33, 31, 52, 35, 18, 58, 56, 39, 45, 59 in CIN 2‐3 and by HPV 18, 33 45, 31, 39, 52, 35, 51, 56 in cancer. HPV 16 and 18 were associated with a significantly increased cancer risk and HPV 52 and 31 with decreased cancer risk compared to the risk of CIN 3. The HPV distribution differed between histological cancer types, stages and age groups. The number of HPV types was not a significant predictor of cancer. Oncogenic HPV types were found in all persistent or recurrent CIN 2‐3 disease after conization. Vaccination against HPV 16/18 is estimated to achieve a minimum 40% reduced rate of CIN 2‐3 and a minimum 60% reduced cancer rate. This rate could, however, be increased to 95% and 92% respectively by including all the 12 HPV types tested for in this study.

Effectiveness of cervical cancer screening in Iceland, 1964–2002: a study on trends in incidence and mortality and the effect of risk factors

Background. Data on cervical cancer screening programs that have covered a whole nation over a prolonged time are scarce. The effectiveness of a 40‐year established nationwide cervical screening program has been evaluated to define optimal age limits and screening intervals. Methods. Trends in incidence and mortality by calendar time, age, histology, stage and attendance during 1964–2002 and the predictive power of calendar year, age, stage and histology on the cause‐specific mortality rate were analyzed. Results. The rate of squamous cell carcinoma decreased significantly, but the rate of adenocarcinoma increased. The age‐specific incidence and cause‐specific mortality decreased significantly for all age groups except those women aged 20–29 years. An increased age‐specific incidence rate, confined to stage I, was observed in the age group 20–39 years after 1980 and a positive correlation was observed between early attendance and the rate of microinvasive squamous (stage IA) cell carcinoma and adenocarcinoma in this age group. The cumulative incidence of invasive disease started to increase two years after the last negative smear. Stage was the strongest risk factor, followed by age and calendar time, and to a lesser degree histology. Conclusions. The results confirm the effectiveness of the screening program and support the recommendation that screening should commence below age 25 with a maximum of 3‐year initial screening intervals. The interval can then be extended after age 40 and stopped after age 65.

Trends in cervical intra-epithelial neoplasia in Iceland through 1995, Evaluation of targeted age groups and screening intervals

BACKGROUNDnTargeted age groups and screening intervals are dependent on the age-specific prevalence of the preclinical disease and the length of the detectable pre-clinical phase. This study evaluates the UICC and EC recommendations regarding targeted age group and screening intervals based on the Icelandic screening experience.nnnMETHODSnThe trends for cytologic preinvasive lesions were analyzed at first visit during the period 1966-1995, at second and later visits after a normal test(s) taken after 1985, and finally at any visit in 1991-1995. The frequency of histologic lesions was calculated for the birth cohort from the age of 60 and among women referred for colposcopic examination in 1994.nnnRESULTSnThe prevalence of preinvasive disease has increased significantly since 1980, and the rate of moderate to high-grade cytologic and histologic lesions begins increasing as early as 20 years of age. The rate of these lesions starts to accumulate at 24 to 36 months after a normal smear, but the rate decreases with the number of negative smears taken. Among correctly screened women the rate of histologically verified moderate to high-grade lesions and invasive disease is practically non-existent after the age of 60, while among the younger women cases with microinvasive disease start to appear within 2 to 3 years after a normal smear.nnnCONCLUSIONnScreening should start soon after age 20 with a screening interval of 2 to 3 years. The screening interval can probably be extended to 4 years at the age of 50 and stop at the age of 60 to 64 among regularly screened women.

Bleomycin‐mitomycin C in advanced carcinoma of the cervix: A third look

Thirty‐three patients with advanced cervical cancer (31 squamous cancer, two adenosquamous cancer) previously untreated with cytotoxic drugs, were treated with bleomycin, 5 mg daily, for seven days and mitomycin C, 10 mg, on day 8. This regimen was repeated four times at two‐week intervals. All but one patient had previously been treated with radiotherapy; 36% of the patients had an objective response (five complete remission (CR), median duration 12 months; seven partial remission (PR), median duration six months). Severe myelosuppression occurred in nine patients. One drug‐related death due to thrombocytopenia occurred. Three patients developed pulmonary fibrosis and one of them died of respiratory failure. The bleomycin‐mitomycin C regimen has a definite but clearly limited effect in advanced cancer of the uterine cervix.

Cervical cancer, Pap smear and HPV testing: an update of the role of organized Pap smear screening and HPV testing.

The objectives of cervical cancer screening are to lower the incidence and mortality rates of the disease. Human papilloma virus (HPV) is stated to be the main etiological factor in preinvasive and invasive disease and HPV testing has been stated to be of value in cervical cancer screening (1). This review discusses different aspects of cervical carcinoma and HPV, evaluates the effectiveness of cervical Pap smear screening and HPV testing, the International Union Against Cancer (UICC) recommendations on targeted age groups (t.a.g.: 25–60 year age group) and the screening interval (s.i.: 3– 5 years) (2), the European guidelines for quality assurance in cervical cancer screening (3), and the Nordic screening experience through 1995.

Longitudinal trends in cervical cytological lesions and the effect of risk factors. A 30-year overview

Background. Cytological preinvasive changes are important precursors in cervical cancer, therefore variations in their trends affect screening guidelines. Methods. Trends in cytological preinvasive changes following the 1st to 5th screening visits in the 20–34 and 35–69 year age groups were analyzed for the period 1979–2002: a) the incidence rate (absolute risk) of higher grade cytology and the relative risk of risk factors on this rate; b) the cumulative incidence of low‐grade and higher grade smears after normal and abnormal screening results; c) the cumulative incidence of higher grade cytology at a fixed risk level after normal screening results; and d) the prevalence of higher grade smears at first screening visit in the 20–24/25–29 year age groups during 1971–2002. Results. An increased trend in the prevalence of higher‐grade smears was observed at the first screening visit after 1980. The main risk variables for higher‐grade smears in both age groups were low‐grade changes and inflammation followed in the younger age group by calendar year. However, age correlated with a decreased risk ratio. After normal screening the cumulative incidence rate of low and higher‐grade smears increased almost linearly with time. The screening interval before diagnosis of higher‐grade smears increased with both age and number of normal visits, but leveled out after the age of 35–40. Conclusions. Trends in higher‐grade smears indicate that screening should preferably start before age 25 with a maximum interval of 3 years. The interval can be extended after age 35–40. Low‐grade smears or inflammation need closer follow‐up.

HPV subtypes and immunological parameters of cervical cancer in Iceland during two time periods, 1958-1960 and 1995-1996

OBJECTIVEnCervical cancer is a disease caused in part by an infection with an oncogenic subtype of human papillomavirus (HPV). In this study we analysed all cervical cancer samples diagnosed in Iceland during two periods, 1958-1960 and 1995-1996, and asked whether significant changes in viral or immunological parameters had occurred over a period that spanned both significant changes in sexual attitude and the implementation of organized screening for cervical cancer.nnnMETHODSnSamples from 47 patients (46 squamous cell carcinomas (SCC) and 1 adenosquamous carcinoma (ASC)) in the first period and 30 patients (20 SCC, 4 ASC, and 6 adenocarcinomas (AC)) in the later period were analysed for viral subtype and expression of Fas, FasL, MHC class I, p53 and apoptosis.nnnRESULTSnAC and ASC are proportionately much more common today than 40 years ago (30% vs 2%). The distribution of HPV in cervical cancer is similar in both periods, with HPV16 found in 75% and HPV18 in 13% of cases. Other HPV types found were 31,33,45, and 59. No significant differences were found in the immunological profiles of tumors from the two periods except that a higher fraction of SCC in the later period stained positive for FasL. When SCC are compared with AC/ASC, the latter have less expression of MHC class I, less expression of Fas, and stronger FasL expression.nnnCONCLUSIONSnAC/ASC tumors show some immunological features that suggest that they are more resistant to immune attack than SCC.

Longitudinal trends in cervical histological lesions (CIN 2–3 + ): A 25-year overview

Background. Trends in CIN 2–3+ lesions affect the choice of target age group and screening interval. Methods. The following analyses were performed for CIN 2_/3_/ following 1st to 5th screening visits in the 20–34/35–69 age groups during 1979–2002: a) the relative risk of age and calendar year; b) the cumulative incidence rate after normal or low or higher grade cytology; c) the proper screening interval to detect these lesions at a fixed risk level after normal screening visits; d) the predictive power of these lesions for diagnosis of cancer after first biopsy; e) the prevalence rates in the 20–24/25–29 year age groups at first and at al1 subsequent screening visits. Results. The cumulative rate decreased with the number of screening visits and advancing age. After normal and low‐grade cytology the cumulative rate increased linearly but slowly with time but after higher grade cytology the rate was relatively stable within one year. Age and calendar year are important risk factors in younger women. The prevalence of CIN 2–3+ increased significantly at 1st visit in the 20–24 age group at the same time as the population prevalence in the 25–29 age group decreased significantly. CIN 2 was at lower risk than CIN 3 of being diagnosed with cancer. Conclusions. The results indicate that screening should preferably start before age 25 with a maximum interval of 3 years, whereas the interval can be extended to 4–/5 years at age 35–40. CIN 2 have a different risk profile compared to CIN 3.