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Johansson H.,Lund University | Bjelkenkrantz K.,Regional Cancer Center South | Darlin L.,Skane University Hospital | Dilllner J.,Karolinska Institutet | Forslund O.,Lund University
PLoS ONE | Year: 2015

Objective: Continuous expression of E6- and E7-oncogenes of high-risk human papillomavirus (HPV) types is necessary for the development and maintenance of the dysplastic phenotype. The aim of the study was to determine the sensitivity and specificity of the APTIMA HPV mRNA assay (Hologic) in predicting future development of high-grade cervical intraepithelial neoplasia (CIN) among high-risk HPV-DNA-positive women with atypical squamous cells of undetermined significance (ASCUS) or low-grade squamous epithelial lesion (LSIL) cytology. Methods: Archived SurePath cervical samples of women ≥ 35 years of age with high-risk HPV DNA-positive ASCUS (n = 211) or LSIL, (n = 131) were tested for the presence of high-risk HPV E6/E7 mRNA using the APTIMA HPV assay, and the women were monitored for development of histopathologically verified CIN2+. Results: Twenty-nine percent (61/211) of the women in the ASCUS group, and 34.3%(45/131) in the LSIL group developed CIN2+ within 4.5 years of follow-up. The prevalence of HPV mRNA was 90.0%(95% CI 85.9-94.0) among women with ASCUS and 95.4% (95% CI 91.8-99.0) among women with LSIL. The presence of HPV E6/E7 mRNA was associated with future development of CIN2+ among women with ASCUS and LSIL (p=0.02). The mRNA assay demonstrated high sensitivity in predicting future CIN2+ and CIN3 for index ASCUS (96.7%; 95% CI 87.6-99.4 and 100%; 95%CI 82.2-100, respectively) and LSIL (97.8%, 95%CI 86.8-99.9 and 100%, 95%CI 79.9-100, respectively). The corresponding specificity was low, 12.7% (95% CI 7.9-19.3) and 5.8%(95%CI 2.2-13.6), for future CIN2+, respectively. The negative predictive value of the HPV mRNA assay for detecting future CIN3 was 100%, since no mRNA-negative woman developed CIN3 (0/27) as compared to 13.6%(43/315) of the mRNA-positive women (p = 0.03). Conclusion: The APTIMA mRNA assay demonstrated high sensitivity but low specificity in predicting future CIN2+ among women with minor cytological abnormalities. The assay had high negative predictive value for future CIN3, indicating that HPV-mRNA-negative women are at low risk of progression to high grade CIN. © 2015 Johansson et al.


Jerlstrom T.,Orebro University | Gardmark T.,Danderyd Hospital | Carringer M.,Orebro University | Holmang S.,Sahlgrenska University Hospital | And 6 more authors.
Scandinavian Journal of Urology | Year: 2014

Objective. Cystectomy combined with pelvic lymph-node dissection and urinary diversion entails high morbidity and mortality. Improvements are needed, and a first step is to collect information on the current situation. In 2011, this group took the initiative to start a population-based database in Sweden (population 9.5 million in 2011) with prospective registration of patients and complications until 90 days after cystectomy. This article reports findings from the first year of registration. Material and methods. Participation was voluntary, and data were reported by local urologists or research nurses. Perioperative parameters and early complications classified according to the modified Clavien system were registered, and selected variables of possible importance for complications were analysed by univariate and multivariate logistic regression. Results. During 2011, 285 (65%) of 435 cystectomies performed in Sweden were registered in the database, the majority reported by the seven academic centres. Median blood loss was 1000 ml, operating time 318 min, and length of hospital stay 15 days. Any complications were registered for 103 patients (36%). Clavien grades 1-2 and 3-5 were noted in 19% and 15%, respectively. Thirty-seven patients (13%) were reoperated on at least once. In logistic regression analysis elevated risk of complications was significantly associated with operating time exceeding 318 min in both univariate and multivariate analysis, and with age 76-89 years only in multivariate analysis. Conclusions. It was feasible to start a national population-based registry of radical cystectomies for bladder cancer. The evaluation of the first year shows an increased risk of complications in patients with longer operating time and higher age. The results agree with some previously published series but should be interpreted with caution considering the relatively low coverage, which is expected to be higher in the future. © 2014 Informa Healthcare.


Stromberg U.,Gothenburg University | Stromberg U.,Lund University | Holmen A.,Development and Education | Peterson S.,Regional Cancer Center South
Spatial and Spatio-temporal Epidemiology | Year: 2016

Screening strategies need to consider differences in late-stage disease detection linked to socio-demographic and geographic factors. We specifically addressed disparity in melanoma stage at diagnosis linked to residential municipality, gender and marital status within the middle- and old-age population of southern and western Sweden. Population-based registers were used to identify the melanoma cases diagnosed in 2004-2013 (n=7,417). Disease mapping for each population group based on gender and marital status showed marked spatial disparities in melanoma incidences and the overall patterns differed by stage at diagnosis. The incidence of early-stage melanoma was markedly higher in the western region, whereas the incidence of late-stage melanoma was markedly higher in the southern region except for married women. Excess mortality among cases was observed to be higher in the southern than in the western region, with significant regional differences for the married male cases and the unmarried female cases. © 2016 Elsevier Ltd.


Nilsson M.P.,Skane University Hospital | Hartman L.,Lund University | Kristoffersson U.,Lund University | Johannsson O.T.,Reykjavik University | And 5 more authors.
Breast Cancer Research and Treatment | Year: 2014

The purpose of the study was to compare breast-conserving therapy (BCT) and mastectomy (M) in BRCA1/2 mutation carriers. Women with invasive breast cancer and a pathogenic mutation in BRCA1 or BRCA2 were included in the study (n = 162). Patients treated with BCT (n = 45) were compared with patients treated with M (n = 118). Endpoints were local recurrence as first recurrence (LR), overall survival (OS), breast cancer death, and distant recurrence. Cumulative incidence was calculated in the presence of competing risks. For calculation of hazard ratios and for multivariable analysis, cause-specific Cox proportional hazards regression was used. Compared to M, BCT was associated with an increased risk of LR in univariable analysis (HR 4.0; 95 % CI 1.6–9.8) and in multivariable analysis adjusting for tumor stage, age, and use of adjuvant chemotherapy (HR 2.9; CI 1.1–7.8). Following M, all local recurrences were seen in the first 5 years after breast cancer diagnosis. Following BCT, the rate of LR continued to be high also after the first 5 years. The cumulative incidence of LR in the BCT group was 15, 25, and 32 % after 5, 10, and 15 years, respectively. There were no significant differences between BCT and M for OS, breast cancer death, or distant recurrence. BRCA1/2 mutation carriers treated with BCT have a high risk of LR, many of which are new primary breast cancers. This must be thoroughly discussed with the patient and is an example of how rapid treatment-focused genetic testing could influence choice of treatment. © 2014, The Author(s).


Sartor H.,Lund University | Sartor H.,Skane University Hospital | Borgquist S.,Lund University | Borgquist S.,Skane University Hospital | And 4 more authors.
Breast | Year: 2015

Our aim was to study how breast density relates to tumor characteristics in breast cancer with emphasis on mode of detection. Among 17,035 women in the Malmö Diet and Cancer Study 826 incident cases have been diagnosed (1991-2007). Data on tumor characteristics, mode of detection, and density at diagnosis were collected. Associations between density and tumor characteristics were analyzed using logistic and ordinal logistic regression models yielding OR and 95% CI. Adjustments for age at diagnosis, BMI at baseline, and the mode of detection, were performed. In denser breasts, large tumor size was more frequent (ORadj 1.59 (1.26-2.01)) as was lymph node involvement (ORadj 1.32 (1.00-1.74)). Further, the higher the density, the lower the grade (ORadj 0.73 (0.53-1.02) for having higher grade), in screening-detected invasive breast cancer. Our findings stress the importance of considering the impact of density in mammography image interpretation and the possible associations with tumor aggressiveness. © 2014 Elsevier Ltd.

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