CineECG for visualization of changes in ventricular electrical activity during ischemia.

BACKGROUND: CineECG offers a visual representation of the location and direction of the average ventricular electrical activity throughout a single cardiac cycle, based on the 12­lead ECG. Currently, CineECG has not been used to visualize ventricular activation patterns during ischemia. PURPOSE: To determine the changes in ventricular activity during acute ischemia with the use of CineECG, and relating this to changes in the ECG. METHODS: Continuous ECG's during percutaneous coronary intervention with prolonged balloon inflation from the STAFF III database were analyzed with CineECG at baseline and every 10 s throughout the first 150 s of balloon inflation. The CineECG direction was determined for the initial QRS-complex, terminal QRS-complex, ST-segment and T-wave. Changes in the CineECG were quantified by calculating the Δangle between the direction at baseline and the direction at every 10 s of inflation. Additionally, the root mean square amplitude (rmsA) of the ST-segment was computed. RESULTS: 94 patients were included. At start inflation, the median Δangle was 14.7° [7.5-33.4], 21.8° [11.4-34.2], 20.6° [8.0-43.9], and 23.5° [11.8-48.0] for the initial QRS-complex, terminal QRS-complex, ST-segment and T-wave, respectively. Meanwhile, the median rmsA increased from 0.039 mV [0.027-0.058] at baseline to 0.045 mV [0.033-0.075] at start of inflation. CONCLUSIONS: CineECG was able to detect immediate changes in ventricular electrical activity during induced ischemia, while changes in the ST-segment of the ECG were still subtle. Therefore, CineECG might support the early detection of acute ischemia, even before distinct ECG changes become visible.

Modeling ventricular repolarization gradients in normal cases using the equivalent dipole layer.

Background Electrical activity underlying the T-wave is less well understood than the QRS-complex. This study investigated the relationship between normal T-wave morphology and the underlying ventricular repolarization gradients using the equivalent dipole layer (EDL). Methods Body-surface-potential-maps (BSPM, 67­leads) were obtained in nine normal cases. Subject specific MRI-based anatomical heart/torso-models with electrode positions were created. The boundary element method was used to account for the volume conductor effects. To simulate the measured T-waves, the EDL was used to apply different ventricular repolarization gradients: a) transmural, b) interventricular c) apico-basal and d) all three gradients (a-c) combined. The combined gradient (d) was optimized using an inverse procedure (Levenberg-Marquardt). Correspondence between simulated and measured T-waves was assessed using correlation coefficient (CC) and relative difference (RD). Results Realistic T-waves were simulated if repolarization times of: (a) the epicardium were smaller than the endocardium; (b) the left ventricle were smaller than the right ventricle and (c) the apex increased towards the base. The apico-basal gradient resulted in the highest correspondence between measured and simulated T-waves (CC = 0.84(0.81-0.91);RD = 0.68(0.60-0.71)) compared to a transmural gradient (CC = 0.77(0.71-0.80);RD = 1.46(0.82-1.75)) and an interventricular gradient (CC = 0.71(0.67-0.80);RD = 0.85(0.75-0.87)). All three gradients combined further improved the correspondence between measured and simulated T-waves (CC = 0.83(0.82-0.89);RD = 0.60(0.51-0.63)), especially after optimization (CC = 0.96(0.94-0.98);RD = 0.27(0.22-0.34)). Conclusion The application of all repolarization gradients combined resulted in the largest agreement between simulated and measured T-waves, followed by the apico-basal repolarization gradient. With these findings, we will optimize our EDL-based inverse procedure to assess repolarization abnormalities.

Longitudinal humoral response after SARS-CoV-2 vaccination in ocrelizumab treated MS patients: To wait and repopulate?

OBJECTIVE: The objective of this study was to measure humoral responses after SARS-CoV-2 vaccination in MS patients treated with ocrelizumab (OCR) compared to MS patients without disease modifying therapies (DMTs) in relation to timing of vaccination and B-cell count. METHODS: OCR treated patients were divided into an early and a late group (cut-off time 12 weeks between infusion and first vaccination). Patients were vaccinated with mRNA-1273 (Moderna). B-cells were measured at baseline (time of first vaccination) and SARS-CoV-2 antibodies were measured at baseline, day 28, 42, 52 and 70. RESULTS: 87 patients were included (62 OCR patients, 29 patients without DMTs). At day 70, seroconversion occurred in 39.3% of OCR patients compared to 100% of MS patients without DMTs. In OCR patients, seroconversion varied between 26% (early group) to 50% (late group) and between 27% (low B-cells) to 56% (at least 1 detectable B-cell/µL). CONCLUSIONS: Low B-cell counts prior to vaccination and shorter time between OCR infusion and vaccination may negatively influence humoral response but does not preclude seroconversion. We advise OCR treated patients to get their first vaccination as soon as possible. In case of an additional booster vaccination, timing of vaccination based on B-cell count and time after last infusion may be considered.

Reduced humoral immune response after BNT162b2 coronavirus disease 2019 messenger RNA vaccination in cancer patients under antineoplastic treatment.

BACKGROUND: Cancer patients are at a higher risk of developing severe coronavirus disease 2019 (COVID-19). However, the safety and efficacy of COVID-19 vaccination in cancer patients undergoing treatment remain unclear. PATIENTS AND METHODS: In this interventional prospective multicohort study, priming and booster doses of the BNT162b2 COVID-19 vaccine were administered 21 days apart to solid tumor patients receiving chemotherapy, immunotherapy, targeted or hormonal therapy, and patients with a hematologic malignancy receiving rituximab or after allogeneic hematopoietic stem cell transplantation. Vaccine safety and efficacy (until 3 months post-booster) were assessed. Anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) receptor-binding domain (RBD) antibody levels were followed over time (until 28 days after the booster) and in vitro SARS-CoV-2 50% neutralization titers (NT50) toward the wild-type Wuhan strain were analyzed 28 days after the booster. RESULTS: Local and systemic adverse events (AEs) were mostly mild to moderate (only 1%-3% of patients experienced severe AEs). Local, but not systemic, AEs occurred more frequently after the booster dose. Twenty-eight days after the booster vaccination of 197 cancer patients, RBD-binding antibody titers and NT50 were lower in the chemotherapy group {234.05 IU/ml [95% confidence interval (CI) 122.10-448.66] and 24.54 (95% CI 14.50-41.52), respectively} compared with healthy individuals [1844.93 IU/ml (95% CI 1383.57-2460.14) and 122.63 (95% CI 76.85-195.67), respectively], irrespective of timing of vaccination during chemotherapy cycles. Extremely low antibody responses were seen in hematology patients receiving rituximab; only two patients had RBD-binding antibody titers necessary for 50% protection against symptomatic SARS-CoV-2 infection (<200 IU/ml) and only one had NT50 above the limit of detection. During the study period, five cancer patients tested positive for SARS-CoV-2 infection, including a case of severe COVID-19 in a patient receiving rituximab, resulting in a 2-week hospital admission. CONCLUSION: The BNT162b2 vaccine is well-tolerated in cancer patients under active treatment. However, the antibody response of immunized cancer patients was delayed and diminished, mainly in patients receiving chemotherapy or rituximab, resulting in breakthrough infections.

No influence of sarcopenia on survival of ovarian cancer patients in a prospective validation study.

OBJECTIVE: Decrease in skeletal muscle index (SMI) during neoadjuvant chemotherapy (NACT) has been associated with worse outcome in patients with advanced ovarian cancer. To validate these findings, we tested if a decrease in SMI was a prognostic factor for a homogenous cohort of patients who received NACT in the randomized phase 3 OVHIPEC-trial. METHODS: CT-scans were performed at baseline and after two cycles of neoadjuvant chemotherapy in stage III ovarian cancer patients. The SMI (skeletal muscle area in cm2 divided by body surface area in m2) was calculated using SliceOMatic software. The difference in SMI between both CT-scans (ΔSMI) was calculated. Cox-regression analyses were performed to analyze the independent effect of a difference in SMI (ΔSMI) on outcome. Log-rank tests were performed to plot recurrence-free (RFS) and overall survival (OS). The mean number of adverse events per patient were compared between groups using t-tests. RESULTS: Paired CT-scans were available for 212 out of 245 patients (87%). Thirty-four of 74 patients (58%) in the group with a decrease in ΔSMI and 73 of 138 of the patients (53%) in the group with stable/increase in ΔSMI had died. Median RFS and OS did not differ significantly (p = 0.297 and p = 0.764) between groups. Patients with a decrease in SMI experienced more pre-operative adverse events, and more grade 3-4 adverse events. CONCLUSION: Decreased SMI during neoadjuvant chemotherapy was not associated with worse outcome in patients with stage III ovarian cancer included in the OVHIPEC-trial. However, a strong association between decreasing SMI and adverse events was found.

A high neutrophil-lymphocyte ratio and platelet-lymphocyte ratio are associated with a worse outcome in inflammatory breast cancer.

INTRODUCTION: Inflammatory breast cancer (IBC) is an uncommon, but aggressive form of breast cancer that accounts for a disproportionally high fraction of breast cancer related mortality. The aim of this study was to explore the peripheral immune response and the prognostic value of blood-based biomarkers, such as the neutrophil-to-lymphocyte ratio (NLR), in a large IBC cohort. PATIENTS & METHODS: We retrospectively identified 127 IBC patients and collected lab results from in-hospital medical records. The differential count of leukocytes was determined at the moment of diagnosis, before any therapeutic intervention. A cohort of early stage (n = 108), locally advanced (n = 74) and metastatic breast cancer patients (n = 41) served as a control population. RESULTS: The NLR was significantly higher in IBC compared to an early stage breast cancer cohort, but no difference between IBC patients and locally advanced breast cancer patients was noted. In the metastatic setting, there was also no significant difference between IBC and nIBC. However, a high NLR (>4.0) remained a significant predictor of worse outcome in IBC patients (HR: 0.49; 95% CI: 0.24-1.00; P = .05) and a lower platelet-lymphocyte ratio (PLR) (≤210) correlated with a better disease-free survival (DFS) (HR: 0.51; 95% CI: 0.28-0.93; P = .03). CONCLUSION: Patients with a high NLR (>4.0) have a worse overall prognosis in IBC, while the PLR correlated with relapse free survival (RFS). Since NLR and PLR were not specifically associated with IBC disease, they can be seen as markers of more extensive disease.

The rationale of opportunistic bilateral salpingectomies (OBS) during benign gynaecological and obstetric surgery: a consensus text of the Flemish Society of Obstetrics and Gynaecology (VVOG).

Ovarian cancer (OC), is a disease difficult to diagnose in an early stage implicating a poor prognosis. The 5-year overall survival in Belgium has not changed in the last 18 years and remains 44 %. There is no effective screening method (secondary prevention) to detect ovarian cancer at an early stage. Primary prevention of ovarian cancer came in the picture through the paradigm shift that the fallopian tube is often the origin of ovarian cancer and not the ovary itself. Opportunistic bilateral salpingectomy (OBS) during benign gynaecological and obstetric surgery might have the potential to reduce the risk of ovarian cancer by as much as 65 %. Bilateral risk-reducing salpingectomy during a benign procedure is feasible, safe, appears to have no impact on the ovarian function and seems to be cost effective. The key question is whether we should wait for a RCT or implement OBS directly in our daily practice. Guidelines regarding OBS within our societies are therefore urgently needed. Our recommendation is to inform all women without a child wish, undergoing a benign gynaecological or obstetrical surgical procedure about the pro's and the con's of OBS and advise a bilateral salpingectomy. Furthermore, there is an urgent need for a prospective registry of OBS. The present article is the consensus text of the Flemish Society of Obstetrics and Gynaecology (VVOG) regarding OBS.

Biochemically Silent Sympathetic Paraganglioma, Pheochromocytoma, or Metastatic Disease in SDHD Mutation Carriers.

CONTEXT: Current guidelines do not consistently recommend imaging beyond the head and neck region in succinate dehydrogenase subunit D (SDHD) mutation carriers as long as catecholamine metabolite levels are within the reference range. PARTICIPANTS: We report a series of 10 patients carrying pathogenic variants in the SDHD gene from five tertiary referral centers for paraganglioma (PGL) in the Netherlands, who presented with a sympathetic PGL (sPGL), pheochromocytoma (PHEO), or metastases outside the head and neck region in the absence of excessive catecholamine production. Two of six patients with a biochemically silent sPGL/PHEO developed metastatic disease. Additionally, four patients were found to have metastases outside the head and neck region from head and neck PGL. The average interval between the initial diagnosis and discovery of the silent lesions was 10 (range, 0 to 32) years. CONCLUSIONS: The absence of excessive catecholamine production does not exclude the presence of manifestations of SDHD outside the head and neck region. These findings suggest that a more extensive imaging strategy in SDHD mutation carriers may be warranted for detection of biochemically silent lesions.

Infiltrating stromal immune cells in inflammatory breast cancer are associated with an improved outcome and increased PD-L1 expression.

BACKGROUND: Inflammatory breast cancer (IBC) is a rare and rapidly progressive form of invasive breast cancer. The aim of this study was to explore the clinical evolution, stromal tumour-infiltrating lymphocytes (sTIL) infiltration and programmed death-ligand 1 (PD-L1) expression in a large IBC cohort. PATIENTS AND METHODS: Data were collected prospectively from patients with IBC as part of an international collaborative effort since 1996. In total, 143 patients with IBC starting treatment between June 1996 and December 2016 were included. Clinicopathological variables were collected, and sTIL were scored by two pathologists on standard H&E stained sections. PD-L1 expression was assessed using a validated PD-L1 (SP142) assay. A validation cohort of 64 patients with IBC was used to test our findings. RESULTS: Survival outcomes of IBC remained poor with a 5-year overall survival (OS) of 45.6%. OS was significantly better in patients with primary non-metastatic disease who received taxane-containing (neo)adjuvant therapy (P = 0.01), had a hormone receptor-positive tumour (P = 0.001) and had lower cN stage at diagnosis (P = 0.001). PD-L1 positivity on immune cells (42.9%) was higher in IBC than in non-IBC in both our patient samples and the validation cohort. Furthermore, PD-L1 expression predicted pCR (P = 0.002) and correlated with sTIL infiltration (P < 0.001). sTIL infiltration of more than 10% of the stroma was a significant predictor of improved OS (HR 0.47, 95% CI 0.27-0.81, P = 0.006) in a multivariate model. CONCLUSIONS: IBC is characterised by poor survival and high PD-L1 immunoreactivity on sTIL. This suggests a role for PD1/PD-L1 inhibitors in the treatment of IBC. Furthermore, we showed that PD-L1 expression predicts response to neo-adjuvant therapy and that sTIL have prognostic significance in IBC.

A SIX1 homolog in Fusarium oxysporum f.sp. cubense tropical race 4 contributes to virulence towards Cavendish banana.

The fungus Fusarium oxysporum f.sp. cubense (Focub) causes Fusarium wilt of banana. Focub strains are divided into races according to their host specificity, but which virulence factors underlie these interactions is currently unknown. In the F. oxysporum f.sp. lycopersici (Fol)-tomato system, small secreted fungal proteins, called Six proteins, were identified in the xylem sap of infected plants. The Fol Six1 protein contributes to virulence and has an avirulence function by activating the I-3 immune receptor of tomato. The Focub tropical race 4 (TR4) genome harbors three SIX1 homologs: SIX1a, b and c. In this study, the role of Focub-SIX1a in pathogenicity was evaluated since this homolog is present in not only TR4 but also in other races. A deletion mutant of the SIX1a gene from Focub TR4 strain II5 was generated (FocubΔSIX1a) and tested in planta. Mutants were found to be severely compromised in their virulence. Ectopic integration of the Focub-SIX1a gene in the FocubΔSIX1a strain restored virulence to wild type levels. We conclude that Focub-SIX1a is required for full virulence of Focub TR4 towards Cavendish banana.

Retrospective Analysis of an Insulin-to-Liraglutide Switch in Patients with Type 2 Diabetes Mellitus.

INTRODUCTION: Insulin and the GLP-1 receptor agonist liraglutide are both effective in reaching glycemic targets. The efficacy of an insulin-to-liraglutide switch in an obese population with concurrent use of sulfonylurea and metformin is unknown. We assessed the efficacy and determinants of success of an insulin-to-liraglutide switch in these patients. METHODS: In a retrospective study we analyzed all patients that underwent an insulin-to-liraglutide switch during routine medical care (January 2009-February 2015). It was assessed if patients still continued liraglutide 12 months after the switch or discontinued because of poor glycemic control or side effects. Baseline characteristics were compared between the groups to establish determinants of success. RESULTS: A total of 104 patients made an insulin-to-liraglutide switch (43% male; mean age 57.2 ± 9.9 years; mean BMI 39.8 ± 5.4 kg/m2). Sixty patients still continued liraglutide after 12 months (58%) whereas 37 patients discontinued treatment because of poor glycemic control within 12 months (36%) and seven patients discontinued liraglutide because of intolerable side effects (7%). Insulin dose and insulin frequency at baseline were significantly lower in patients that continued liraglutide. Patients reaching HbA1c ≤ 7% (53 mmol/mol) showed lower baseline HbA1c levels, shorter duration of diabetes, and shorter duration of insulin therapy. CONCLUSION: The majority of patients continued liraglutide after a switch from insulin therapy with on average no change in glycemic control and decrease of body weight. HbA1c levels at baseline, duration of insulin therapy, and duration of diabetes were predictive of reaching glycemic control on liraglutide alone. In current practice this also indicates which patients on insulin can reduce their insulin dose after adding a GLP-1 receptor agonist. Plain language summary available for this article.

Time trends (2006-2015) of quality indicators in EUSOMA-certified breast centres.

AIM OF THE STUDY: The European Society of Breast Cancer Specialists (EUSOMA) has fostered a voluntary certification process for breast centres to establish minimum standards and ensure specialist multidisciplinary care. Prospectively collected anonymous information on primary breast cancer cases diagnosed and treated in the units is transferred annually to a central EUSOMA data warehouse for continuous monitoring of quality indicators (QIs) to improve quality of care. Units have to comply with the EUSOMA Breast Centre guidelines and are audited by peers. The database was started in 2006 and includes over 110,000 cancers from breast centres located in Germany, Switzerland, Belgium, Austria, The Netherlands, Spain, Portugal and Italy. The aim of the present study is assessing time trends of QIs in EUSOMA-certified breast centres over the decade 2006-2015. MATERIALS AND METHODS: Previously defined QIs were calculated for 22 EUSOMA-certified breast centres (46122 patients) during 2006-2015. RESULTS: On the average of all units, the minimum standard of care was achieved in 8 of 13 main EUSOMA QIs in 2006 and in all in 2015. All QIs, except removal of at least 10 lymph nodes at axillary clearance and oestrogen receptor-negative tumours (T > 1 cm or N+) receiving adjuvant chemotherapy, improved significantly in this period. The desirable target was reached for two QIs in 2006 and for 7 of 13 QIs in 2015. CONCLUSION: The EUSOMA model of audit and monitoring QIs functions well in different European health systems and results in better performance of QIs over the last decade. QIs should be evaluated and adapted on a regular basis, as guidelines change over time.

Is there a role for urokinase-type plasminogen activator inhibitors as maintenance therapy in patients with ovarian cancer?

There is abundant evidence that the urokinase-type plasminogen activator (uPA), its inhibitors PAI-1 and PAI-2 (plasminogen activator inhibitor type-1 and type-2) and its cells surface receptor (uPA-R, CD87) play a fundamental role in tumor invasion and metastasis and are of significant prognostic significance for many tumor types. We performed a systematic Med-line search on uPA, PAI, uPA-R and (epithelial) ovarian cancer (EOC). The majority of malignant EOC specimens show moderate to strong immunostating of tumor and stromal cells. Overexpression of u-PA and PAI-1 can be found in more the 75% of primary ovarian carcinomas, in most metastatic EOC samples and all examined epithelial ovarian cancer cell lines. uPA overexpression in primary specimens was significantly associated with tumor stage, grade, residual disease status after cytoreductive surgery, and poor clinical outcome. This may be explained by increased chemoresistance, a lower resectability and more aggressive tumor biology and tumor dissemination in patients with high uPA and PAI-1. Several therapeutical approaches aimed at inhibiting the uPA/uPAR functions have shown to possess anti-tumor effects in vitro and in animal models. When treating a patient with advanced ovarian cancer it may to be assumed that inhibiting the progression of established (micro) metastases may be more therapeutically relevant than trying to destroy all tumor cells which is not possible in most cases with current systemic treatment modalities. Taking into account the role of uPA and PAI in cell detachment, formation of new stroma, tumor cell reimplantation and metastasis uPA inhibition should be further investigated as maintenance treatment in patients with advanced EOC.

Current and future role of circulating tumor cells in patients with epithelial ovarian cancer.

Circulating tumor cells (CTCs) are viable tumor cells that are released into the circulatory system. CTCs have shown a prognostic value in numerous solid tumors. CTC research in epithelial ovarian carcinoma (EOC) has attracted only little attention. Since the primary route of metastasis in EOC is considered to be direct peritoneal spread in the abdominal cavity and distant metastases only occur in one third of the patients, it was thought that there is not enough shedding of tumor cells in the circulation. Nevertheless recent studies revealed an important role of hematogenous spread in EOC and showed that CTC status is associated with advanced tumor stage, CA-125 levels and residual disease after surgery. Furthermore the presence of CTCs correlates with shorter overall and disease free survival. However this prognostic value of CTCs in EOC seems to depend on the used isolation and detection methods. In EOC function- or density based enrichment methods seem to offer more promising results then epithelial cell adhesion molecule (EpCAM)-based approaches. This can be explained by a low number of EpCAM positive CTCs in EOC and the downregulation of EpCAM during epithelial-to-mesenchymal transition (EMT). The presence of CTCs might also have predictive value as CTC status was associated with treatment response in two studies and CTCs showed to be a better monitoring tool then CA-125 in a small population. The (genotypic) characterization of CTCs might become even more important in the future paving the way for CTCs to a true predictive "liquid tumor biopsy".

Neoadjuvant endocrine treatment in early breast cancer: An overlooked alternative?

During the last decade neoadjuvant endocrine therapy (NET) has moved from being reserved for elderly and frail non-chemotherapy candidates to a primary systemic modality in selected patients with hormone sensitive breast cancer. Neoadjuvant hormonal treatment in patients with hormone receptor positive, HER-2 negative early breast cancer is proven to be an effective and safe option; it is associated with a higher rate of breast conserving surgery (BCS), may reduce the need for adjuvant chemotherapy and enables a delay of surgery for medical or practical reasons. Clinical responses range from 13% to 100% with at least 3 months of NET. Methods of assessing response should include MRI of the breast, particularly in lobular tumours. In studies comparing tamoxifen with aromatase inhibitors (AI), AI proved to be superior in terms of tumour response and rates of BCS. Change in Ki67 is accepted as a validated endpoint for comparing endocrine neoadjuvant agents. Levels of Ki67 during treatment are more closely related to long-term prognosis than pretreatment Ki67. Neoadjuvant endocrine therapy provides a unique opportunity for studies of endocrine responsiveness and the development of new experimental drugs combined with systemic hormonal treatment.

The effect of EUSOMA certification on quality of breast cancer care.

AIM OF THE STUDY: The European Society of Breast Cancer Specialists (EUSOMA) has fostered a voluntary certification process for breast units to establish minimum standards and ensure specialist multidisciplinary care. In the present study we assess the impact of EUSOMA certification for all breast units for which sufficient information was available before and after certification. MATERIALS AND METHODS: For 22 EUSOMA certified breast units data of 30,444 patients could be extracted from the EUSOMA database on the evolution of QI's before and after certification. RESULTS: On the average of all units, the minimum standard of care was achieved for 12/13 QI's before and after EUSOMA certification (not met for DCIS receiving just one operation). There was a significant improvement of 5 QI's after certification. The proportion of patients with invasive cancer undergoing an axillary clearance containing >9 lymph nodes (91.5% vs 89.4%, p 0.003) and patients with invasive cancer having just 1 operation (83.1% vs 80.4%, p < 0.001) dropped, but remained above the minimum standard. The targeted standard of breast care was reached for the same 4/13 QI's before and after EUSOMA certification. CONCLUSION: Although the absolute effect of EUSOMA certification was modest it further increases standards of care and should be regarded as part of a process aiming for excellence. Dedicated units already provide a high level of care before certification, but continuous monitoring and audit remains of paramount importance as complete adherence to guidelines is difficult to achieve.

A cross-sectional, multicentre, epidemiological study on human papillomavirus (HPV) type distribution in adult women diagnosed with invasive cervical cancer in Belgium.

OBJECTIVE: Despite an advanced national cervical cancer screening and vaccination programme cervical cancer is still the third most frequent diagnosed gynaecological tumour in Belgium. The goal of this study is to present the Belgian data of a cross-sectional, multicentre, epidemiological study on human papillomavirus (HPV) type distribution in adult women diagnosed with invasive cervical cancer (ICC) conducted in 12 European countries. MATERIAL AND METHODS: Centres in four major Belgian cities (Antwerp, Brussels, Ghent and Liège) participated in this study. Tissue samples from women with ICC were collected from the period 2001 - 2008. All slides were centrally reviewed and analysed for HPV. The total enrolled cohort included 278 subjects. RESULTS: The histologically eligible cohort comprised of 255 patients (mean age 51.3 ± 15.1 years) and 237 were confirmed HPV positive (mean age 50.6 ± 14.9 years). A single HPV infection was present in 95.8%. The five most frequent HPV types were HPV 16 (68.7%), HPV18 (12.3%), HPV 31 (6.2%), HPV 33 (5.3%) and HPV 45 (1.8%). Multiple HPV types were present in 3.4%, with two HPV types in 2.5% and three HPV types in 0.8%. In the various HPV type combinations observed in multiple infected women, HPV 31 (62.5%) and HPV 33 (50.0%) were the most frequent. The ratio of adenocarcinoma (ADC) versus squamous cell carcinoma (SCC) cases in the histologically eligible cohort was 1:8. Compared to the pooled European data the Belgium HPV 16 is 1.1, HPV 33 is 1.2 and HPV 31 is 1.7 higher and the HPV 18 is 0.8 and HPV 45 is 0.34 lower. CONCLUSION: The 5 most frequent HPV types in Belgium are the same as in the rest of Europe, but the distribution is different. Cervical cancer screening should therefore be HPV type specific and HPV prophylactic vaccination should also focus on other types then HPV 16 and HPV 18. A national registry is needed in order to follow the trends of HPV types in the society and to measure the impact of prevention, for which the data presented in this study can be an important basis.