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ABSTRACT: The development of targeted therapies has created a pressing clinical need for molecular characterisation of cancers. In this retrospective study, high-resolution melting analysis (HRMA) was validated and implemented for screening of 164 colorectal cancer (CRC) patients to detect KRAS hot-spot mutations and to evaluate its prognostic value. Direct sequencing was used to confirm and characterise HRMA results.
After establishing its sensitivity, HRMA was validated on seven cell lines and inter- and intra-variation were analysed. The prognostic value of KRAS mutations in CRC was evaluated using survival analysis.
HRMA revealed abnormal melting patterns in 34.1% CRC samples. Kaplan-Meier survival curves revealed a significantly shorter overall (OS) and disease-free survival (DFS) for CRC patients harbouring a KRAS mutation. In the Cox regression analysis, only when colon and rectal cancer were analysed separately, KRAS mutation was a negative predictor for OS in patients with rectal cancer and DFS in those with stage II colon cancer.
HRMA was found to be a valid screening method for KRAS mutation detection. The KRAS mutation came forward as a negative predictive factor for OS in patients with rectal cancer and for DFS in stage II colon cancer patients.
British Journal of Cancer 10/2010; 103(10):1627-36. · 5.04 Impact Factor
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European Respiratory Journal 07/2010; 36(1):213. · 5.89 Impact Factor
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ABSTRACT: Magnetic resonance (MR) arthrography is generally regarded as the gold standard for shoulder imaging. As an alternative to direct MR arthrography, the less invasive indirect MR arthrography technique was proposed, offering logistic advantages because fluoroscopic or ultrasonographic guidance for joint injection is not required.
To assess the diagnostic performance of indirect MR arthrography in the diagnosis of full- and partial-thickness supraspinatus tears in a symptomatic population.
Two radiologists with different levels of experience independently and retrospectively interpreted indirect MR (1.5T) arthrograms of the shoulder obtained in 67 symptomatic patients who underwent subsequent arthroscopy. On MR, the supraspinatus tendon was evaluated for full- or partial-thickness tear. With arthroscopy as the standard of reference, sensitivity, specificity, and diagnostic accuracy of indirect MR arthrography in the detection of full- and partial-thickness tears of the supraspinatus tendon was calculated. Kappa (kappa) statistics were used for the assessment of the agreement between arthroscopic and imaging findings and for the assessment of interobserver agreement.
For full-thickness tears of the supraspinatus tendon, sensitivities, specificities, and accuracies exceeded 90% for both observers, with excellent interobserver agreement (kappa = 0.910). For partial-thickness tears, sensitivities (38-50%) and accuracies (76-78%) were poor for both reviewers, and interobserver agreement was moderate (kappa = 0.491). Discrepancies between MR diagnosis and arthroscopy were predominantly observed with small partial-thickness tears.
Indirect MR arthrography is highly accurate in the diagnosis of full-thickness rotator cuff tears. However, the diagnosis of partial-thickness tears with indirect MR arthrography remains faulty, because exact demarcation of degenerative change and partial rupture is difficult. On the basis of the above findings, we do not recommend indirect MR arthrography on patients for whom rotator cuff disease is suspected clinically.
Acta Radiologica 11/2009; 50(9):1057-63. · 1.37 Impact Factor
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ABSTRACT: Persistent wheeze is a common chronic disease in early childhood and later may progress to asthma. However, the association between pre- and post-bronchodilator lung function and the wheezing phenotype in preschool children is not known. Children 4 yrs of age involved in a prospective birth cohort study (in Antwerp, Belgium) concerning perinatal factors and the occurrence of asthma and allergies, were invited to participate in lung function measurements with the forced oscillation technique. The wheezing phenotype was assessed via (bi)annual questionnaires. Wheezing phenotype and baseline respiratory impedance data were available for 325 children, 96% of whom underwent bronchodilation tests. The baseline resistance at 4 Hz was higher in children with early transient (11.0 hPa x s x L(-1), n = 127) or persistent wheeze (11.9 hPa x s x L(-1), n = 54) than in children who never wheezed (10.3 hPa x s x L(-1), n = 144). After bronchodilation, the resistance decreased on average by 22%. The decrease was greater among the persistent wheezers than among those who never wheezed (3.4 versus 2.3 hPa x s x L( -1)). The baseline lung function was poorer and the bronchodilator response was greater in 4-yr-old children with persistent wheeze than in those who never wheeze or who had early transient wheeze, implying a higher bronchomotor tone in the former group.
European Respiratory Journal 11/2009; 35(4):865-72. · 5.89 Impact Factor
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ABSTRACT: Endothelial dysfunction is a known precursor of atherosclerosis and can be assessed by measuring the brachial artery flow-mediated dilatation (FMD) via ultrasonography. This study investigated endothelial function in young type 1 diabetics without cardiovascular morbidity or diabetes-related pathology.
Young diabetics and healthy controls were recruited, both meeting strict inclusion and exclusion criteria. To prove absence of subclinical atherosclerosis, intima-media thickness (IMT) measurements at the carotid bifurcation were done in all of them. FMD was measured at the brachial artery. The results were compared using the t-test and the influences of different variables on FMD were assessed using multiple linear regression.
Twenty-six diabetics (23.4+/-5.8 years) and 36 healthy volunteers (23.1+/-2.8 years) were recruited. The duration of diabetes was 9.2+/-5.3 years; metabolic control was moderate (HbA1c 7.6+/-1.0%) and IMT was normal in both groups. FMD was significantly impaired in type 1 diabetics (7.13+/-0.43 vs. 8.77+/-0.43%; p=0.002). The FMD grade was associated with diabetes and age. Patients with a good metabolic control (HbA1c</=7.0%) had a better FMD.
In type 1 diabetics, even without preclinical or clinical atherosclerosis, endothelial function is already disturbed and can be detected using ultrasonography.
European journal of vascular and endovascular surgery: the official journal of the European Society for Vascular Surgery 03/2009; 37(5):611-5. · 2.92 Impact Factor
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ABSTRACT: To determine the role of magnetic resonance (MR) mammography in detection and assessment of extent of tumors with extensive intraductal component (EIC+).
In a prospective study, 233 consecutive women with a suspicious lesion underwent preoperative MR mammography and 209 invasive ductal carcinomas were detected. We studied the prediction of intraductal spread on mammography (MX), ultrasound (US) and MR. We compared the size of the total lesion on MX, US and MR and correlated it with histopathology. Enhancement patterns on MR were described.
Of 209 invasive ductal carcinomas, 50 were EIC+ (24%). MX predicted intraductal spread in EIC+ carcinomas in 48.5%, US in 34.2% and MR in 68%. Compared to MX and US, MR was best in assessment of total tumor size. On MR, ductal spread in EIC+ tumors presented as ductal or linear enhancement, long spicules, a regional enhancing area or nodules adjacent to a mass.
MR had the highest sensitivity to predict intraductal spread and was superior in assessing total tumor size.
European Journal of Radiology 06/2007; 62(2):273-82. · 2.61 Impact Factor
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European Journal of Clinical Microbiology 10/2004; 23(9):735-7. · 2.86 Impact Factor
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P Sardari Nia,
C Colpaert,
B Blyweert,
B Kui,
P Vermeulen,
M Ferguson,
J Hendriks, J Weyler,
F Pezzella,
E Van Marck,
P Van Schil
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ABSTRACT: An essential prerequisite of nonangiogenic growth appears to be the ability of the tumour to preserve the parenchymal structures of the host tissue. This morphological feature is visible on a routine tissue section. Based on this feature, we classified haematoxylin and eosin-stained tissue sections from 279 patients with non-small-cell lung cancer into three growth patterns: destructive (angiogenic; n=196), papillary (intermediate; n=38) and alveolar (nonangiogenic; n=45). A Cox multiple regression model was used to test the prognostic value of growth patterns together with other relevant clinicopathological factors. For overall survival, growth pattern (P=0.007), N-status (P=0.001), age (P=0.020) and type of operation (P=0.056) were independent prognostic factors. For disease-free survival, only growth pattern (P=0.007) and N-status (P<0.001) had an independent prognostic value. Alveolar (hazard ratio=1.825, 95% confidence interval=1.117-2.980, P=0.016) and papillary (hazard ratio=1.977, 95% confidence interval=1.169-3.345, P=0.011) growth patterns were independent predictors of poor prognosis. The proposed classification has an independent prognostic value for overall survival as well as for disease-free survival, providing a possible explanation for survival differences of patients in the same disease stage.
British Journal of Cancer 10/2004; 91(7):1293-300. · 5.04 Impact Factor
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ABSTRACT: The enhancing area surrounding breast carcinoma on MR mammography is correlated with findings from pathological examination. We studied 194 patients with breast cancer who underwent preoperative MR mammography. Of all malignant lesions presenting with an enhancing surrounding area on MR mammography, morphologic features including long spicules, a ductal pattern, diffuse enhancement or nodules were evaluated and compared with histopathological examination. A double breast coil was used; we performed a 3D FLASH sequence with contiguous coronal slices of 2 mm, before and after injection of 0.2 mmol/kg GD-DTPA, and subtraction images were obtained. In total, 297 malignant lesions were detected at MR mammography and 101 of them had one or more types of enhancing surrounding area. In 49 of the 53 cancers with long spicules and in 49 of the 55 cancers with surrounding ductal pattern of enhancement, pathological examination showed in situ and/or invasive carcinoma. Multiple nodules adjacent to the carcinoma were seen in 20 patients and corresponded with six cases of invasive and ten cases of ductal in situ carcinoma. A diffuse enhancing area next to a mass was seen in ten patients and consisted of carcinoma in all cases: seven in situ and three invasive carcinomas. Enhancing areas including long spicules, a ductal pattern, noduli, or diffuse enhancement surrounding a carcinoma corresponded with in situ or invasive extension of the carcinoma in 92.5, 89, 80 and 100% of cases, respectively.
European Radiology 09/2004; 14(8):1363-70. · 3.22 Impact Factor
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ABSTRACT: The aim of this study was to determine whether pre-operative MR mammography could predict the extent of breast cancer in patients with dense breasts or whether dense parenchyma will lead to false-positive or inconclusive examinations. Sixty-seven patients with dense breasts with a malignant breast tumor planned for conservative surgery were reviewed. Detection rates of mammography, ultrasound, and MR mammography were studied, and the diameters of the lesions were measured and compared with pathological examination. Pathology revealed breast cancer in 65 patients. Sensitivity for detection of index lesions was 83% for mammography, 70.8% for ultrasound, and 98% for MR mammography. Mammography underestimated tumor extent in 37%, ultrasound in 40%, and MR in 12.5%. Of the 20 patients (31%) with multifocal or multicentric carcinoma, mammography detected the lesions in 35%, ultrasound in 30%, and MR in 100%, with a false-positive rate of 12.5, 14, and 23%. The MR mammography is more accurate in assessing tumor extent and multifocality in patients with dense breasts, but benign changes may lead to false-positive examinations.
European Radiology 06/2004; 14(5):809-16. · 3.22 Impact Factor
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ABSTRACT: The aim of this study was to determine whether pre-operative MR mammography could predict the extent of breast cancer in patients with dense breasts or whether dense parenchyma will lead to false-positive or inconclusive examinations. Sixty-seven patients with dense breasts with a malignant breast tumor planned for conservative surgery were reviewed. Detection rates of mammography, ultrasound, and MR mammography were studied, and the diameters of the lesions were measured and compared with pathological examination. Pathology revealed breast cancer in 65 patients. Sensitivity for detection of index lesions was 83% for mammography, 70.8% for ultrasound, and 98% for MR mammography. Mammography underestimated tumor extent in 37%, ultrasound in 40%, and MR in 12.5%. Of the 20 patients (31%) with multifocal or multicentric carcinoma, mammography detected the lesions in 35%, ultrasound in 30%, and MR in 100%, with a false-positive rate of 12.5, 14, and 23%. The MR mammography is more accurate in assessing tumor extent and multifocality in patients with dense breasts, but benign changes may lead to false-positive examinations.
European Radiology 04/2004; 14(5):809-816. · 3.22 Impact Factor
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ABSTRACT: Human papillomavirus (HPV) is present in the vast majority of high-grade gynecological abnormalities (high-grade squamous intraepithelial lesions and worse) and, therefore, HPV detection has a very high negative predictive value. Nevertheless, introduction of HPV detection into primary screening would result in large numbers of false positives: HPV positive women with normal cytology. The prevalence of HPV in women with cytologically normal smears is age-dependent as has been shown extensively. We hypothesize that women at the age of 50, who are HPV negative and have a cytologically normal smear might be encouraged to refrain from further screening. The data available from the literature on HPV prevalence in elderly women is presented. Data of cohort studies of elderly women with and without HPV infection as well as health-economical analyses to investigate the cost-effectiveness of the proposed hypothesis are still lacking.
European journal of gynaecological oncology 02/2004; 25(6):665-9. · 0.47 Impact Factor
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ABSTRACT: Tropisetron treatment was compared with alizapride treatment. The secondary aim was to assess whether droperidol supplement would still improve the therapeutic outcome of tropisetron.
A series of 51 obese patients was treated with an intragastric balloon to obtain weight reduction. Patients were divided at random into 3 groups. Each group received a different antiemetic and spasmolytic regimen to control postoperative nausea and vomiting for 24 hours. Statistical analysis of both parameters showed that all 3 populations are comparable and the studied incidence of vomiting was only influenced by the choice of the antiemetics used. A specially developed form was completed during the recovery period every 6 hours until 24 hours postoperatively and recorded all episodes of vomiting. The incidence of vomiting was then calculated as number of episodes/24 hours Results: The incidence of vomiting was significantly lower in the tropisetron group compared to the alizapride group. There was no significant difference between the tropisetron group and the tropisetron plus droperidol group.
To decrease the incidence of vomiting in patients undergoing intragastric balloon placement, tropisetron proved to be the most effective antiemetic. A supplement of droperidol gave no better results but impaired postoperative mood and wellbeing. Alizapride was least effective.
Obesity Surgery 01/2004; 13(6):932-7. · 3.29 Impact Factor
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ABSTRACT: To examine the importance of a fibrotic focus-a scar-like area in a carcinoma-as a marker of intratumoral hypoxia that correlates with angiogenesis and with clinical outcome in node-negative breast cancer.
One hundred and four T1-2N0M0 breast carcinoma patients were divided into two groups: group 1 (n=46) showing early distant relapse (median disease-free survival 25 months) and group 2 (n=58) showing no evidence of disease (median follow-up 91.5 months). All tumours were evaluated for medial/lateral location, size, histological grade, mitotic activity, necrosis, fibrotic focus, angiogenesis, vascular permeation and growth pattern. Multiple regression analysis showed that only histological grade and the presence of a fibrotic focus were independent predictors of early distant relapse. A fibrotic focus was present in 53% of the tumours. The relative size (fibrotic focus/tumour ratio) was significantly correlated with an unfavourable outcome. The presence of necrosis inside the fibrotic focus and the absolute and relative size of the fibrotic focus were significantly correlated with angiogenesis. A fibrotic focus was significantly associated with large, expansively growing tumours with high histological grade and numerous mitoses.
A fibrotic focus can be used as a surrogate for quantifying angiogenesis and is an independent predictor of early metastasis in lymph node-negative breast cancer.
Histopathology 11/2001; 39(4):416-25. · 3.08 Impact Factor
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ABSTRACT: A case-control study was designed to determine the possible association between chronic exposure to dioxins and polychlorinated biphenyls (PCBs), and the occurrence of endometriosis. The study group consisted of 42 infertile endometriosis cases and 27 mechanical infertile controls, both groups attending one of the collaborating Centres for Reproductive Medicine, enrolled between 1996-1998.
Exposure assessment to dioxin-like compounds was determined through CALUX (chemical-activated luciferase gene expression)-bioassay to measure dioxin-like total toxic equivalents (dioxins and co-planar PCBs), whereas non-co-planar PCBs were determined through chemical analysis.
No association was found between median dioxin-like total toxic equivalents (TEQ) and the occurrence of endometriosis in infertile women [cases (n = 34): 29; controls (n = 27): 24; NS]. When patients were subdivided based on an arbitrary cut-off value of 100 pg TEQ/g serum lipids, no statistically significant association between very high exposure to dioxin-like compounds and endometriosis was found [crude odds ratio (OR) = 4.33; confidence interval (CI) 0.49-38.19; NS]. After adjusting for body mass index, and alcohol consumption, the risk increased slightly to OR = 4.6 (CI 0.48-43.62; NS). There was no confounding by age, ovulatory dysfunction, caffeine intake, smoking or exposure to non-co-planar PCBs.
The study results showed no statistically significant association between exposure to dioxin-like compounds and the occurrence of endometriosis in infertile women.
Human Reproduction 11/2001; 16(10):2050-5. · 4.47 Impact Factor
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ABSTRACT: Early distant relapse occurs in a minority of node-negative breast cancer patients. Whether this poor prognosis can be predicted by the features of the primary tumour, or by the presence of occult metastases in the "negative" lymph nodes (LNs), remains a matter of debate. One hundred and four T(1-2)N(0)M(0) breast carcinoma patients were divided into two groups: group 1 (44%) showing early distant relapse with a median disease-free survival of 25 months, and group 2 (56%) showing no evidence of disease after a median follow-up of 91.5 months. All patients had received locoregional treatment only. All tumours were evaluated for medial/lateral location, histological type, size, grade, mitotic activity, fibrotic focus, necrosis, angiogenesis, growth pattern, and lymphatic vessel permeation. The haematoxylin and eosin-stained slides of all axillary LNs were revised and two additional levels were cut from each paraffin block for cytokeratin immunohistochemistry. In 24 patients (23%), occult metastases were found. These consisted of single cells or small clusters (SCs) in the marginal sinus in 17 patients (16%) and of larger colonies of cells in seven patients (7%). All detected metastases were smaller than 2 mm in diameter (micrometastases). There was no significant correlation between the presence of occult LN metastases (SCs or colonies) and the prognostically important features of the primary tumour. Early metastatic disease was significantly correlated with larger tumour size (p=0.02), higher histological grade (p=0.0008), mitotic activity (p<0.0001), presence of necrosis (p=0.0004), presence of fibrotic foci (p=0.0005), angiogenesis (p=0.0009), and lymphatic vessel permeation (p=0.018). Multiple logistic regression analysis showed that histological grade and the presence of a fibrotic focus were the only independent prognostic factors and that the presence of occult LN metastases was inversely correlated with early distant relapse. Prospective prognostic studies of occult LN metastases should consider the features of the primary tumour in a multivariate analysis.
The Journal of Pathology 05/2001; 193(4):442-9. · 6.32 Impact Factor
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ABSTRACT: To evaluate the proliferation activity in CIN III lesions and Ia1 carcinoma according to the risk of recurrence.
The proliferation markers PCNA (proliferating cell nuclear antigen) and mitotic index were studied in 75 patients with CIN III and in 20 patients with an Ia1 squamous carcinoma of the cervix by staining representative tissue sections for the PCNA and assessing the mitotic index. Associations between the studied proliferation markers and various histopathologic characteristics as well as recurrence were assessed.
Three groups of PCNA were constituted: <20, 20--40, > OR =40% positive tumour nuclei, which contained, respectively, 45 (47%), 29 (31%), and 21 (22%) patients. Microinvasive carcinomas have a higher proliferation activity than CIN III (PCNA P=0.005; mitotic index P=0.094). For CIN III, there was a significantly lower risk for recurrence in the group with lower mitotic activity, compared to the group with higher mitotic activity (Kaplan-Meier: log-rank testing P=0.044). Significance was, however, not reached for the different PCNA categories (Kaplan-Meier, log-rank test P=0.068). Multiple regression analysis showed that in our population of CIN III lesions, only age of diagnosis and treatment modality were relevant (independent) prognostic indicators for recurrence.
In CIN III lesions there is evidence for an association between proliferation activity and the risk of recurrence. The observed crude association weakens when adjusting for age at diagnosis and treatment modality. Apparently this feature is associated with more aggressive biological behaviour and could be used to identify women who are at higher risk of recurrence.
European Journal of Obstetrics & Gynecology and Reproductive Biology 03/2001; 94(2):270-5. · 1.97 Impact Factor
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ABSTRACT: The aim of the study was to find out which factors can predict the outcome of conservative treatment of urinary stress incontinence in women. One hundred and four women with stress urinary incontinence were evaluated by recall, and by clinical and urodynamic investigation and were given pelvic floor muscle exercises with or without the use of biphasic low-frequency electrostimulation and visual biofeedback. Two groups could be distinguished. The first consisted of 37 patients in whom conservative therapy proved successful; the second consisted of 67 patients in whom incontinence continued. The study investigated whether there was a significant difference in patients' characteristics between the two groups. The number of conservative treatment sessions was not different between the two groups. The presence of a high body mass index, previous pelvic surgery, strong levator muscles and urethral hypermobility appeared to be poor prognostic features. More research is required to evaluate which patients can benefit from conservative treatment and which criteria can predict the outcome of pelvic floor physiotherapy in women with stress incontinence. This way, patients selection is possible and excessive costs can be saved.
International Urogynecology Journal 02/2001; 12(6):386-90. · 1.83 Impact Factor
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M F Baay,
W A Tjalma, J Weyler,
G G Pattyn,
H A Lambrechts,
G Goovaerts,
M Baekelandt,
P Buytaert,
E A Van Marck,
F Lardon,
J B Vermorken
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ABSTRACT: To investigate the relation between the prevalence of human papillomavirus (HPV) and age in cervical cancer patients, material from 93 patients with Ia-IIb cervical carcinoma was analyzed for the presence of HPV by both type-specific and general primer polymerase chain reaction. Patients were divided into 2 groups: 64 years or younger, and 65 years and older. There was no statistically significant difference in either the prevalence of HPV DNA or distribution of genotypes amongst the 2 groups. Therefore, HPV detection can be equally well used in the management and follow-up of elderly cervical cancer patients.
Gynecologic and Obstetric Investigation 02/2001; 52(4):248-51. · 1.28 Impact Factor
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ABSTRACT: Worldwide there is a strong relation between the presence of human papillomavirus (HPV) and the development of cervical cancer. This study investigated the prevalence and genotype of HPV in women with normal smears, women with premalignant lesions and women with cervical cancer in Antwerp, Belgium. Type-specific polymerase chain reaction (PCR) for HPV types 16 and 18 and general primer PCR (GP5+/6+) was performed on DNA extracted from paraffin-embedded tissue from women with lesions or fresh material from controls. HPV was detected in 11% of controls, 61% of women with atypia, 77% of women with CIN lesions and 88% of women with cervical carcinoma (chi2 trend, 273, p<0.001). The odds ratio for high-risk HPV types was 9.3 for atypia (95%CI. 4.3-19.8), 33.6 for CIN lesions (95%CI, 19.3-58.6) and 78.8 for cervical cancer (95%CI, 39.2-158.3). In total, 19 different HPV genotypes were detected, including five low risk HPV types. Seven of the 14 high-risk HPV types were detected in cervical cancer patients. Based on our study it is suggested that a prophylactic vaccine based on a cocktail of a limited number of high-risk HPV types should be considered in order to protect most women from developing cervical cancer.
European journal of gynaecological oncology 01/2001; 22(3):204-8. · 0.47 Impact Factor
