[show abstract][hide abstract] ABSTRACT: The aim of the study was to compare the histological outcome of the cone specimens with the diagnoses of the preoperative biopsies, to assess the distribution of histological features consistent with human papillomavirus (HPV) infection and, finally, to analyse the impact of cellular HPV features on classification of cervical intraepithelial neoplasia (CIN). The study comprised a population of 317 women treated for CIN by laser conization during the period 1983-85. A total of 634 cervical specimens (317 preoperative biopsies and their corresponding cones) were studied retrospectively for CIN classification and examined for morphological signs of HPV infection. For presentation of the results, we used a modified terminology for CIN. Low-grade (LG) CIN included borderline lesions and CIN I, while high-grade (HG) CIN included CIN II and CIN III. The blinded histopathological review revealed HG CIN both in the preoperative biopsies and the cones in 71% of the cases. LG CIN or benign lesions were found in the preoperative biopsies and their corresponding cone specimens in 6% of the study population. HPV features were present in 65% of the preoperative biopsies, and were most prevalent in women under 29 years of age (p<0.001). Thirteen percent of the total biopsy material was downgraded. The downgrading was most prevalent among original CIN II (p=0.009) and HPV-negative biopsies (p<0.001). This study demonstrates that CIN lesions are frequently associated with HPV features, which are significantly more prevalent in the youngest women. Concomitant HPV features do not influence the CIN classification.
[show abstract][hide abstract] ABSTRACT: The population of gynaecological cancer survivors is growing. However, there is little knowledge of the long-term quality of life among these former patients. The aim of this study was to investigate the long-term quality of life in women treated successfully for gynaecological cancer and a control group of representative women selected from the general population.
The study comprised women aged 30-75 years residing in the central part of Norway. Cases were 319 gynaecological cancer survivors treated at St Olav's Hospital Trondheim, Norway, between 1987 and 1996, whereas 1276 age-matched women selected at random from the general population served as controls. The study population was identified and the respondents were invited to answer a postal questionnaire. After one reminder, the response rate was 55% (176/319) and 41% (521/1276) for cases and controls, respectively. Sixteen cases and 28 controls had incomplete responses to most questions and were excluded from the analyses. Eligible for the final analyses were 160 cases and 493 controls. Ferrans & Powers' Quality of Life Index (QLI) was used. All analyses were performed in SPSS version 13.0 with chi-square (categorical variables) and Mann-Whitney (continuous variables) tests. p <or= 0.05 is the level of statistical significance.
Cases had on an average, a complete recurrence-free period of 12 years (range 7-18). No differences were detected between cases and controls in the global quality of life or in any of the four sub-dimensions of QLI. Furthermore, no difference was found in co-morbidity, but cases consulted more often hospital physicians than controls did.
Long-term gynaecological cancer survivors enjoy the same quality of life as women in the general population.
[show abstract][hide abstract] ABSTRACT: To study urinary incontinence among long-term survivors of gynecological cancer.
In a population-based, cross-sectional design, we identified 319 recurrence-free survivors of gynecological cancer, and 1,276 controls without a history of gynecological cancer. All participants were addressed with a 16-pages questionnaire covering issues of quality of life, general health, daily living conditions, natural functions and co-morbidities. Following 1 reminder, the response rates were 55 and 41% for cases and controls, respectively. Urinary incontinence (total, stress, urge and mixed) was in agreement with definitions of the International Continence Society.
Mean relapse-free follow-up time after treatment was 12 years (range: 8-17 years) for cases. The prevalence of total, stress, urge and mixed urinary incontinence were 34.3, 24, 0.8 and 9.5%, respectively. Previous gynecological cancer treatment was not associated with any outcomes of urinary incontinence. Obesity, previous and current use of HRT were associated with total, stress and mixed urinary incontinence, whereas increasing parity order was associated with total and stress urinary incontinence. In comparison with single factor analyses, the combination of obesity and parity 2+ had a multiplicative effect on total, stress and mixed incontinence.
Recurrence-free long-term survivors of gynecological cancer are not at increased risk for urinary incontinence.
[show abstract][hide abstract] ABSTRACT: The Norwegian coordinated cervical cancer screening program invites women from 25 to 69 years of age to have a cytological smear from the cervix uteri analysed every third year. The aim of this study was to identify the volume of smears collected and to evaluate the consequences of having or not having this done for 24-year-old and younger women not included in the screening program and to compare the results with those for other age groups.
Data were obtained from the following Norwegian Cancer Registry sources: the Cancer Registry for incident cases of cancer cervix uteri (1995-2004), the Cytology Registry for volume of cervical specimen collection (1992-2005) and outcome of smears (2004), the CIN-treatment database for the number of incident cases of cervical intraepithelial neoplasia grade 2 or 3 (2004) and the Cervix Histology Registry for histological outcome of cervical biopsies (2004). Data were displayed by age (< or = 24, 25-29, 30-69 and 70 years or older). No statistical testing was done.
Cancer in the cervix uteri is extremely rare among 24 year-old and younger women (0-3 cases per year). The volume of cervix smears taken from young women has decreased over the past 10 years; in 2005 approximately 35,000 out of 440,000 smears came from young women. More smears from young women were inconclusive and more lesions were of low grade than in older women; repeat testing was therefore required more frequently in young women. More young than older women were diagnosed with grade 1 or grade 2 lesions.
Most lesions in young women regress spontaneously. By not collecting smears from young women, many lesions that would anyway regress spontaneously, would not be discovered and follow-up could be avoided. Prospective follow-up studies of viral processes and oncogeneses indicate that it takes many years for normal cervix cells in the uterus to develop into cancer. For most young women it makes no difference whether low grade lesions or lesions that require treatment are diagnosed at age 23, 24 or shortly after 25. With reference to data from the Norwegian Cancer Registry and international literature, we conclude that analysis of cytological cervix smears from young women is more harmful than beneficial.
Tidsskrift for den Norske laegeforening 07/2007; 127(13):1782-5.
[show abstract][hide abstract] ABSTRACT: Patients with epithelial ovarian cancer are often diagnosed with advanced disease; hence they have a generally poor survival rate. The main objective was to assess the clinical effectiveness of the four main treatment options in the primary treatment of epithelial ovarian cancer: i) adjuvant chemotherapy and/or adjuvant radiotherapy, ii) cytoreductive surgery, iii) neoadjuvant chemotherapy in advanced disease, and iv) postoperative chemotherapy in advanced disease.
The scientific literature was identified by searches in Medline, Embase and Cochrane CCTR and by additional manual searches. Using criteria defined by protocol, two reviewers assessed each study according to relevance, quality and validity. Among 2227 publications identified, 635 were read as full-text articles, and 90 studies were critically assessed as relevant publications. All included studies were systematised in three subgroups according to the quality of the study design in question and the validity of the results: high, moderate, or low. A total of 45 studies of high or moderate quality form the documentary basis for this review.
Current data are inconclusive regarding the effect of adjuvant chemotherapy. Retrospective data show a survival advantage for patients who have had maximum cytoreductive surgery. The effect of neoadjuvant chemotherapy is uncertain. Several questions remain unanswered despite wide acceptance of paclitaxel-carboplatin as the current standard in first-line treatment.
This systematic review demonstrates the need for more clinical studies.
Tidsskrift for den Norske laegeforening 03/2005; 125(3):278-81.
[show abstract][hide abstract] ABSTRACT: Cervical intraepithelial neoplasia (CIN) is an established precursor of invasive cervical cancer. Excision procedures such as cold-knife conization, electrodiathermy or laser conization of the cervix are major surgical treatment modalities of CIN.
Women who were treated for CIN 2/3 or suspected invasive cancer with cold-knife conization between 1977 and 1980 (n=212) were compared with women treated with laser conization between 1987 and 1990 (n=439). Outcome parameters were method of anaesthesia, duration of hospital stay, treatment efficacy and postoperative complications such as bleeding, infection or cervical stenosis.
General anaesthesia was used in 88 % of women treated with cold-knife conization, while paracervical block anaesthesia was used in 97 % of women treated with laser conization. Mean hospital stay was 7.6 days after cold-knife conization, while laser conization was performed as an outpatient procedure. The overall complication rate was 36.8 % after cold-knife conization and 8.4 % after laser conization. Significantly higher rates of postoperative bleeding (21.1 % v. 5.0 %), infections (2.6 % v. 0.5 %) and cervical stenosis (11.8 % v. 1.6 %) were found after cold-knife conization compared to laser conization. Treatment efficacy was equally high (98 %) with both methods.
Laser conization was found to be a significantly less resource consuming procedure and with fewer postoperative complications compared to cold-knife conization.
Tidsskrift for den Norske laegeforening 02/2005; 125(2):167-9.
[show abstract][hide abstract] ABSTRACT: To examine the effect of centralized surgery on overall survival in patients with ovarian cancer and, in particular, patients with advanced disease (stage III/IV).
In a historical prospective study design, patients referred from community hospitals to a teaching hospital for primary surgery during the 2-year period, 1995-1997, were included as cases. For each referred case, two controls, matched for International Federation of Gynecology and Obstetrics (FIGO) stage and age, were selected among patients who had had primary surgery at the referral hospitals (nonteaching) in the years, 1992-1995. Kaplan-Meier survival curves were computed and tested statistically by the log rank test. Cox proportional hazard model was applied for estimation of prognostic factors of survival.
There was no difference in postoperative mortality for stage I/II patients by level of care (community hospitals versus teaching hospital). However, for advanced stage disease (III + IV), the controls had significantly shorter crude survival than patients who had been operated on at the teaching hospital (5-year survival: 4% versus 26%; median survival: 12 months versus 21 months) (P=.01). Multivariable analyses showed that completed chemotherapy and size of residual tumor after primary surgery were independent prognostic factors of survival. Patients optimally operated on at the teaching hospital had significantly lower risk of death compared with all other groups, independently of chemotherapy. This indicates that the extent of cytoreductive surgery and the overall management undertaken in the teaching hospital are significant predictors of improved survival.
Centralization of primary ovarian cancer surgery in one health region in Norway has improved survival for patients with advanced disease. Patients with apparent advanced ovarian cancer should be referred to a subspecialty unit for primary surgery, and every effort should be made to attain as complete cytoreduction as possible.
Obstetrics and Gynecology 10/2003; 102(3):499-505. · 4.80 Impact Factor
[show abstract][hide abstract] ABSTRACT: To assess incidence during a 10-year study period and to identify and discuss clinical relevance for prognostic factors of survival within a cohort of Norwegian ovarian cancer patients.
Incidence and prognostic factors of survival within a population-based cohort of ovarian cancer patients from one health region in Norway were examined over the 10-year period 1987 through 1996. A total of 571 histologically verified cases of primary ovarian cancer originally registered either in the Cancer Registry of Norway or in the hospital's discharge registers were included in the study. Pearson chi(2) test was used in univariate analyses of cofactors by 5-year survival, and Kaplan-Meier survival curves were computed and tested statistically by the log rank test. A multivariable proportional hazard model (Cox) was applied to assess the prognostic significance of the different covariates.
The incidence and crude 5-year survival remained stable over the 10-year study period. The standardized incidence rate for the time periods 1987-1991 and 1992-1996 was 11.9/100,000 and 12.5/100,000, respectively. The crude 5-year survival rate for the cohort was 39%, whereas median survival was 32 months. Cox multivariable regression analysis showed that the only independent significant prognostic factors were International Federation of Gynecology and Obstetrics stage (P <.001), size of residual tumor at the end of primary surgery (P <.001), and age at diagnosis (P <.01). Variables such as time period, histologic type and grade, treating hospital, comorbidity, or CA 125 were insignificant in predicting 5-year survival.
The results underline the importance of improved surgical management of ovarian cancer, as residual tumor is the only prognostic factor achievable.
[show abstract][hide abstract] ABSTRACT: Completeness of reporting and accuracy of the diagnosis of ovarian cancer from one health region in Norway to the Cancer Registry were examined. Data kept by the Cancer Registry were evaluated against discharge diagnosis data from all 8 hospitals in the health region during the period of 1987-1996. The assessment of the accuracy of the diagnosis recorded in the Cancer Registry was based on review of all medical records in the hospital setting and on slide review of all histologic diagnoses. The overall completeness of reporting ovarian cancer to the Cancer Registry was 99.6%. The organ specific completeness of registration of histologic verified ovarian cancer within the Cancer Registry was 95.3%; 0.9% was erroneously coded and 3.5% had their diagnosis changed to ovarian cancer at re-evaluation. Of all ovarian cancer cases registered at the Cancer Registry, 91% had a primary histologic diagnosis. Among 591 cases identified with a histologic diagnosis in the Cancer Registry, the accuracy of the diagnosis was estimated at 92%. Coding errors were found in 2% of these cases, while in 6% of the cases it was not possible to reproduce the original diagnosis of ovarian cancer at re-evaluation. In order to provide data of high quality for cancer surveillance a cancer registry needs several data providers, such as histopathologic laboratory reports and clinical reports. In addition, assessment of reported data through stringent quality assurance procedures within the registry are necessary for reaching a nearly 100% completeness of registration as found for ovarian cancer in the Cancer Registry of Norway.
International Journal of Cancer 05/2002; 98(6):907-11. · 6.20 Impact Factor
[show abstract][hide abstract] ABSTRACT: Familial breast-ovarian cancer has been demonstrated to be frequent but unevenly distributed in Norway. This was assumed to be caused by the reduced population size created by the medieval Bubonic plagues 25 generations ago, and by the following rapid expansion. We have previously reported that four mutations account for 68% of the BRCA1 mutation carriers. Subsequent analysis has resulted in a total of 100 separate families carrying one of these founder mutations. The four mutations occurred on one specific BRCA1 haplotype each. The 1675delA, 816delGT and 3347delAG families originated from the South-West coast of Norway with a few families in the north, while the traceable ancestors of the 1135insA families clustered along the historical inland road from the South-East to mid-Norway. The carriers of each of the four mutations today are descendants of one or a few individuals surviving the plagues. We may identify the majority of BRCA1 mutation carriers in Norway by screening for local founder mutations.
European Journal of Cancer 01/2002; 37(18):2428-34. · 5.06 Impact Factor
[show abstract][hide abstract] ABSTRACT: Cervical cancer is the third most frequent cancer among women worldwide. Human papillomavirus (HPV) infection is a necessary risk factor and the first step in cervical carcinogenesis.
This article reviews the current literature concerning the possibility of preventing cervical cancer by HPV testing and vaccination.
HPV testing cannot replace cytology, but will reduce false negative cytology and may improve the screening programme for cervical neoplasia. It has not yet been incorporated in any national cervical cancer screening program, but trials are ongoing in Scandinavia and in the Netherlands. The cost-effectiveness of HPV testing in screening has to be proven and whether it can affect the recommended screening-intervals. Therapeutic and prophylactic vaccines for HPV associated disease are in progress. Evaluating the clinical trials that are ongoing will take several years. Several anti-HPV vaccines are now in clinical trials; Norway will also participate. Therapeutic vaccines against cervical cancer have so far not been successful, but anogenital dysplasias and condylomas may be more susceptible. Prophylactic vaccines against HPV 6, 11, 16 and 18 have been evaluated in clinical phase I and II trials, and phase III trials are in progress.
HPV testing improves the specificity and sensitivity of cervical cytology and it can be used to clarify cases with atypical cells of undetermined significance (ASCUS) and low-grade intraepithelial neoplasia. In the near future it may also be included in the cervical cancer screening programme for women above the age of 30. The first results in clinical vaccine trials are encouraging, and final conclusions about the effectiveness of these vaccines may be achieved in five years' time.
Tidsskrift for Den norske legeforening 11/2001; 121(25):2947-51.
[show abstract][hide abstract] ABSTRACT: To test prospectively the diagnostic performance of two logistic regression models for calculation of individual risk of malignancy in adnexal tumors (the 'Tailor model' and the 'Timmerman model'), and to compare them to that of 'pattern recognition' (subjective evaluation of the gray-scale ultrasound image and color Doppler ultrasound examination).
Consecutive women with a pelvic mass judged clinically to be of adnexal origin underwent preoperative ultrasound examination including color and spectral Doppler examination. The same examination techniques and definitions as those used in the studies in which the logistic regression models had been created were used. The Tailor model was tested in 133 women (35 of whom hada malignancy) and the Timmerman model in 82 women (29 of whom had a malignancy). A subset of 79 women (28 of whom had a malignancy) was used to compare the performance of the Tailor model and the Timmerman model by calculating and comparing the areas under the receiver operating characteristics curves of the two models. Sensitivity and specificity with regard to malignancy were calculated for all three methods.
Pattern recognition performed better than the two logistic regression models (sensitivity around 85%, specificity around 90%). Using a risk of malignancy of > 50% to indicate malignancy (as suggested in the original publications), the sensitivity of the Tailor model was 69% and the specificity 88% (n = 133). The corresponding values for the Timmerman model were 62% and 79% (n = 82). The receiver operating characteristics curves showed the two logistic regression models to have similar diagnostic properties (area under the curve, 0.87 vs. 0.84; P = 0.25; n = 79). The diagnostic performance of the mathematical models was much poorer in this study than in those in which the models had been created.
The poor diagnostic performance of the mathematical models can probably be explained by subtle differences in definitions and examination technique and by differences between the original tumor populations and the study population. For mathematical models to be generally useful, they probably need to be created on the basis of a very large number of tumors, and the variables in the model must be unequivocally defined and the examination technique meticulously standardized.
Ultrasound in Obstetrics and Gynecology 10/2001; 18(4):357-65. · 3.56 Impact Factor
[show abstract][hide abstract] ABSTRACT: The goal of this study was to evaluate the effects of single fractions of 10 Gy pelvic irradiation for palliation and life prolongation in patients with cancer of the uterine cervix or corpus.
A retrospective analysis was performed on 37 cervical cancer and 27 corpus cancer patients treated in the period 1988-1998. All patients had a life expectancy of less than 1 year. Due to stage of disease, age (median 82 years), or comorbidity they were considered unapt for surgery or conventional radiotherapy. Eleven patients with recurrence within irradiated field or early progression received one, 51 patients received two, and 2 patients received three fractions with a 4-week interval.
Vaginal bleeding stopped in 90% and malodorous discharge in 39% of the patients. Among 46 patients with advanced disease treated for palliation, 10 (22%) showed complete tumor responses. Median time to progression was 6 months, and median survival, 9 months. Eighteen patients with early-stage disease and serious comorbidity were treated with life prolongation and symptom prevention as intention, and showed seven complete responses. Median survival was 13 months, and half the deaths were caused by intercurrent disease. Median hospital stay was 5 days and rehabilitation was easy. Fifty-six percent of the patients experienced no acute side effects and 33% had minor gastrointestinal problems. Three patients (6%) had serious late bowel complications, one with a fatal outcome, the symptoms appearing 9-10 months posttreatment.
The 10-Gy single-fraction pelvic radiation regimen is an effective means of symptom palliation and is well tolerated. Tumor responses are obtained. The risk of late bowel complications is a concern for patients with a life expectancy greater than 9 months.
[show abstract][hide abstract] ABSTRACT: Data on the need for palliative care related to disease groups are very limited.
A retrospective analysis was performed on the hospital records of 228 patients who died from gynaecologic cancer during the 1988-1997 period.
76% of deaths took place in hospital; 12% at home. Median terminal hospital stay was 13 days. Symptoms from intestinal obstruction were dominating in 30% of cases and most frequently seen in patients with ovarian cancer. Palliative intestinal surgery was performed in 38% of patients with ovarian cancer, median survival being 5 months (range 10 days-7 years), perioperative mortality (within 30 days) 13%. Cachexia dominated in 27% and was more often present when death occurred at home. Assistance from a gastroenterologic surgeon, urologist, haematologist or anaesthesiologist was needed in 32% of cases. One in two patients received parenteral pain relief in the terminal phase, for a median period of five days. Palliative radiotherapy was given 21% of the patients, most often in cervical and endometrial cancer, and chemotherapy or hormonal therapy was used in 36%. Minor interventions like laparocentesis, pleurocentesis, tumour resections, and various forms of urinary deviations were frequent.
Hospital deaths are more common among patients suffering from gynaecologic cancer than among cancer patients in general (55% in Norway), and the need for multimodal hospital service is large. We see substantial benefits in the Norwegian model in which a gynaecologist experienced in oncology has comprehensive responsibility for the treatment, supported by other specialists and the primary health service.
Tidsskrift for Den norske legeforening 07/2001; 121(16):1896-901.
[show abstract][hide abstract] ABSTRACT: Our objective was to compare the predictive value of the well-established tumour marker CA125 with the newer tumour markers tetranectin (TN), OVX1 and CASA in distinguishing benign and malignant pelvic masses in women. Participants included 185 women, 19 years or older, with a pelvic mass planned for surgical exploration. Significantly different CA125 levels were found between benign tumours and localised ovarian cancer (OC), advanced OC and other non-OCs. Significantly different TN levels were found between benign tumours and advanced OC (stage III/IV), between benign tumours and other cancers and between all OCs and other cancers. For CASA, significant differences were found between benign tumours and all OCs as well as advanced OC. No significant differences could be demonstrated for OVX1. Significant correlations for the 44 OC patients were found between CA125, TN and CASA. No significant correlations were found for OVX1, possibly because of the method used for collection and handling of serum samples. None of the new markers had any additional predictive value compared to CA125. TN and CASA levels correlated with FIGO stage and could be used to discriminate between benign and advanced OC. However, in comparison to the performance of CA125, the additional discriminative value of TN and CASA was minor.
International Journal of Cancer 12/2000; 89(6):519-23. · 6.20 Impact Factor