Till Örebro universitet

OBJECTIVE: With the transition from cytology to human papilloma virus (HPV) testing in cervical cancer screening, it is possible to use self-sampling instead of professionally collected samples. Most studies have included women between 20 and 60 years age. Here we aimed to study postmenopausal women and investigate whether vaginal self-sampling is equally effective as professional sampling for detection of HSIL and the possibility to use a method for molecular triage directly on the screening sample.

METHODS: Postmenopausal women in Örebro county, Sweden, were invited (n = 7835) during 2018-2020 to participate in the study including both professional and self-sampling. In total 2258 women returned both sample types, that were analyzed for HPV followed by triage for cytology, HPV genotyping and methylation and clinical follow-up according to national guidelines.

RESULTS: The prevalence of HPV was 3.4 % in the professionally collected samples and 12.6 % in the self-collected. All women with high-grade squamous intraepithelial lesion (HSIL) were HPV-positive in both professionally and self-collected samples. For self-collected samples, we compared different triage strategies. Cytology was the most efficient strategy. Among the molecular triage methods, the combination of methylation and genotyping was most efficient but resulted in twice as many colposcopy referrals as cytology.

CONCLUSIONS: In conclusion, HPV self-sampling with molecular triage detects HSIL to the same extent as professional screening with cytological triage. The specificity of molecular triage is, however, unacceptably low, and to avoid overtreatment other triage methods following primary self-sampling need to be developed.

Background: Cervical cancer is the most prevalent cancer in Mozambique, with endocervical adenocarcinoma accounting for approximately 5.5% of cases. Knowledge regarding the most prevalent HPV genotypes in endocervical adenocarcinoma is limited, within this setting. This study aimed to investigate human papillomavirus (HPV) prevalence and genotypes within a cohort of endocervical adenocarcinoma patients in the context of Mozambique's recently introduced vaccination programme, considering the country's HIV-endemic setting.

Methods: Forty consecutive cases of endocervical adenocarcinoma diagnosed at Maputo Central Hospital between 2017 and 2018, with limited clinical data available, were included. Human immunodeficiency virus (HIV) status was determined through serological data or in situ hybridisation on histopathological slides. HPV detection was performed using a multi-methodological approach, including Anyplex II, in-house polymerase chain reaction (PCR), and chromogenic and fluorescent in situ hybridisation techniques.

Results: All 40 cases exhibited HPV-dependent morphology. Fourteen of the 40 patients were HIV-positive. No significant differences were observed between the two groups regarding age, stage, or histopathological type. hrHPV16, 18, or 45 were detected in all cases. Notably, multiple hrHPV infections were identified exclusively in HIV-negative cases (10/26, p = 0.0075), with hrHPV18/45 co-infection being the most common (n = 8).

Conclusions: These findings suggest that the newly implemented quadrivalent vaccination programme has the potential to prevent morbidity and mortality from endocervical adenocarcinoma, irrespective of HIV infection status, in Mozambique's HIV-endemic environment.

Vulvar cancer is a rare gynaecological disease that can be caused by infection with human papillomavirus (HPV). The mutational frequencies and landscape for HPV-associated and HPV-independent vulvar tumor development are supposedly two distinctly different pathways and more detailed knowledge on target biological mechanisms for individualized future treatments is needed. The study included formalin-fixed paraffin-embedded (FFPE) samples from 32 cancer patients (16 HPV-negative and 16 HPV-associated), treated in Örebro, Sweden from 1988 to 2008. The Oncomine™ Comprehensive Assay v3 was used to detect variants across 161 different tumor relevant genes. Data analysis included quality assessment followed by variant analysis of DNA with the Oncomine Comprehensive v3 workflow and with a custom filter using the VarSome Clinical software. The RNA-analysis was performed with the Oncomine Comprehensive v3 workflow. Totally, 94% of DNA libraries and 81% of RNA libraries were of adequate quality for further downstream analysis. With the Oncomine™ filter chain there was an increased number of variants in the HPV-negative group (2.5 variants) compared to the HPV-associated group (1.5 variants). Using custom filter and the Varsome Clinical software; additional single nucleotide variants (SNV) were detected where the vast majority were classified as likely benign/benign. HPV-negative tumors had a larger fraction of variants of unknown significance (VUS), and likely pathogenic/pathogenic compared to the HPV-associated tumours. The top 10 frequently mutated genes in HPV-indepentent tumors were TP53, POLE, PTCH1, BRCA2, CREBBP, NOTCH2, ARID1A, CDKN2A, MSH2, and NOTCH1. Three fusion genes were detected; TBL1XR1(1)::PIK3CA(2) (n = 2) and NF1(5)::PSMD11(2) (n = 1). Copy number variations (CNV) were more common in HPV-associated tumors (n = 13/16, 81%) compared to HPV-negative tumors (n = 9/14, 64%). The most frequent CNV was found in the cMYC gene, followed by CDK2 (n = 5) and CDK4 (n = 4). The main outcome of this study show that vulvar cancer harbour genetic variations of different types and specifically, HPV-independent tumours are molecularly very heterogeneous and harboured more SNVs while HPV-associated tumors more frequently presented with gene amplifications. The PI3K/AKT/mTOR1 pathway was affected in both the groups as well as the cell cycle regulation pathway. Similarly, the DNA repair gene POLE was found mutated in both vulvar cancer groups.

Objective: The aim of this study was to investigate if there is a lack of professionals in the Nordic countries as well as the prognosis for the future in relation to educational output. In addition, the study aimed to investigate the Nordic professional’s point of view on how to make the profession attractive, what career opportunities that are needed and what role the BLS should have in the future healthcare setting.

Materials and methods: Data for each country were provided from reports. Professionals present at the NML congress 2023 were invited to discuss questions related to the lack of BLS. Answers were collected, summarized, and grouped in themes.

Results: Three of four Nordic countries report current and future challenges in BLS workforce and a substantial amount of BLS in the Nordic countries are 50 years or older. Despite efforts where admissions to the universities have increased, the amount of examinates has not increased proportionally. Professionals identifies a need for making the profession more attractive highlighting career opportunities, professional visibility, salary increase, and task-shifting.

Discussion: We have identified several threats to the sustention of BLS in healthcare today and in the future in the Nordic countries. This includes high retirement numbers, drift towards working in the private sector, as well as low salaries and lack of career opportunities. In this study, the profession has provided useful insights on how to make the profession more attractive including increased visibility, provide career paths, and distinguish what the BLS competence is and can be in the future.

Conclusion: We have identified several future arenas for the profession that can attract students to educations, keep professionals in healthcare, and secure high quality in diagnostics. To succeed, we need stronger linkage between the profession itself, educational institutions, healthcare employers, and professional organizations.

BACKGROUND: The aim of this study was to examine the natural course of HPV infection in women of 60 years and older who were HPV positive at inclusion, and any association between HPV positivity in historical samples and dysplasia outcome. METHODS: Eighty-nine women aged 60-82 years, who tested positive for HPV between 2012 and 2016 were included. Sampling for cytology and/or histology was also performed. HPV genotyping was carried out on archived material back to 1999.

RESULTS: Of the 89 HPV-positive women 16 had HSIL, 34 had LSIL and 39 were benign at inclusion. Of the women with HSIL, 50.0% had the same HPV type in the archive samples, 12.5% had another type, and 37.5% were HPV negative. Among the 34 women with LSIL, 47.1% had the same HPV type in archive samples, 5.8% had another type, and 47.1% were HPV negative. Of the 39 women without dysplasia at inclusion, 25.6% had the same HPV type in archive samples, 5.1% had another HPV type and 69.2% were HPV negative.

CONCLUSION: Surprisingly few of the elderly women thus seem to have a history with the same or any HPV infection the years before being diagnosed with an HPV infection and dysplasia. The significance of an HPV infection for dysplasia development in elderly women is still not fully understood.

Inguinal lymph node surgery is a standard treatment for penile cancer patients with intermediate or high risk for lymph node metastasis (LNM) according to European Association of Urology (EAU) risk grading. We are proposing a more objective histological prognostic grading system for inguinal LNM in these patients. We assessed worst pattern of invasion, lymphocytic host response, lymphovascular invasion, and perineural invasion in a population-based cohort of 306 penile cancer patients. Patients were classified into low, intermediate, and high risk for inguinal LNM. There was a significant association both between risk groups and pT stage (p < 0.001) and between risk groups and LNM. Univariate logistic regression showed 25.43 times higher odds of LNM for patients in the intermediate risk group compared with the low risk group (odds ratio (OR) 25.43; 95% confidence interval (CI): 5.94-108.97) and a 177.13 times higher odds in the high risk group compared to the low risk group (OR 177.13; 95% CI: 40.09-782.51). When comparing our histological risk grading with the EAU grading, we found a higher sensitivity, of 51.28% (95% CI: 45.68-56.88) versus 37.09% (95% CI: 31.68-42.50), as well as a higher area under the curve (0.86; 95% CI: 0.81-0.89; versus 0.65; 95% CI: 0.58-0.71) with our grading system. While our grading classified 111 patients as low risk, only 31 were considered low risk for LNM according to the EAU risk classification. The new histological risk grading system shows a higher sensitivity and includes a higher number of patients in the low risk group in whom lymph node surgery could be avoided, reducing morbidity and costs.

BACKGROUND: Cervical cancer is a global disease and it is well established that cervical cancer is caused by human papillomavirus (HPV). In Sweden self-sampling for HPV is now used as a complement to sampling performed by a midwife. However, there is a lack of knowledge on how older women perceive the self-sampling compared to the sampling performed by a midwife. Therefore, the aim of the study was to describe how women, aged 64 years and older, perceived the process of self-sampling and sampling performed by a midwife for HPV-testing.

METHODS: Eighteen women were included in a qualitative interview study, and a phenomenographic approach was used for the analysis of the interviews.

RESULTS: Three descriptive categories emerged: Confidence in sampling, Facilitating participation and Being informed. Within the categories, eight conceptions emerged describing the variation relating to how the women perceived the process of self-sampling and sampling performed by a midwife.

CONCLUSIONS: Women in this study describe confidence in self-sampling for HPV-testing and that the self-sampling was saving time and money, both for themselves and for society. Information in relation to an HPV-positive test result is of importance and it must be kept in mind that women affected by HPV may feel guilt and shame, which health care professionals should pay attention to. This knowledge can be used in education of health care staff.

BACKGROUND: With HPV screening the specificity of screening positives has decreased, even with a cytological triage test. Increases in colposcopies and detection of benign or low-grade dysplasia are reported, not least in older women. These results highlight the necessity to find other triage tests in HPV screening strategies, so that women can be more accurately selected for colposcopy, thus minimizing the clinically irrelevant findings.

METHODS: The study included 55- to 59-year-old women who exited the screening with normal cytology, but later in a follow-up test were positive for the HPV genotypes 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66 and 68 and had a cervical cone biopsy done. To model a screening situation with hrHPV-positive women, three different triage strategies, namely, cytology, genotyping and methylation, were performed. The study considered the effect of direct referral to colposcopy for HPV genotypes 16, 18, 31, 33, 45, 52 and 58, and methylation for FAM19A4 and hsa-mir124-2 and/or any form of abnormal cytology.

RESULTS: Seven out of 49 women aged 55-59 years with hrHPV had a cone biopsy with high-grade squamous intraepithelial lesion. No triage method found all cases, and when comparing positive and negative predictive value and false negative rate, cytology showed better results than genotyping and methylation.

CONCLUSION: This study does not support a switch in triage strategies from cytology to hrHPV genotyping and methylation for women above 55 years of age yet, but demonstrates the need for more evidence on molecular triage strategies.

Primary vaginal cancer (PVC) is a rare gynaecological malignancy, which, at present, lacks appropriate biomarkers for prognosis. The proteins dyskerin and WD repeat containing antisense to TP53 (WRAP53β), both of which exert their functions in the telomerase holoenzyme complex, have been shown to be upregulated in different cancer types. These proteins have also been proposed as prognostic markers in some types of cancer. The aim of the present study was to examine the expression patterns of dyskerin and WRAP53β in patients with PVC. Moreover, as part of a search for effective biomarkers to evaluate prognosis in PVC, the expression of these two proteins and their potential association with clinical variables and survival were also evaluated. The expression of dyskerin and WRAP53β was assessed in PVC tumour samples from 68 patients using immunohistochemistry. The majority of tumour samples showed low and moderate expression levels of dyskerin. Upregulation of dyskerin in tumour samples was significantly associated with a shorter survival time and a poorer cancer-specific survival rate. WRAP53β was also expressed in most of the cells but was not significantly associated with clinical variables or survival. This study demonstrates that upregulation of dyskerin is significantly associated with poor prognosis. Thus, dyskerin may serve as a promising prognostic marker and a potential putative therapeutic target in PVC.