Publications by authors named "Jussi Tarkkanen"

45 Publications

Preoperative evaluation and treatment consideration of parotid gland tumors.

Laryngoscope Investig Otolaryngol 2020 Aug 20;5(4):694-702. Epub 2020 Jul 20.

Department of Otorhinolaryngology-Head and Neck Surgery University of Helsinki and Helsinki University Hospital Helsinki Finland.

Background: The nature of parotid tumors often remains unknown preoperatively and final histopathology may reveal unexpected malignancy. Still, the use of fine-needle aspiration cytology (FNAC) and imaging varies in the management of these tumors.

Methods: We evaluated the preoperative examinations and management of all 195 parotid gland tumors diagnosed within our catchment area of 1.6 million people during 2015.

Results: Altogether 171 (88%) tumors were classified as true salivary gland neoplasms. FNAC showed no false malignant findings, but it was false benign in 5 (2.6%) cases. Preoperative MRI was utilized in 48 patients (25%). Twenty (10%) malignancies included 16 salivary gland carcinomas. Pleomorphic adenomas accounted for 52% of all adenomas. For 24 (40%) Warthin tumors, surgery was omitted.

Conclusion: The proportion of malignancies was lower than generally presented. Our proposed guidelines include ultrasound-guided FNAC with certain limitations. MRI is warranted in selected cases, but seems unnecessary routinely.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/lio2.433DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7444776PMC
August 2020

Sclerosing sialadenitis of the submandibular gland is rarely an immunoglobulin G4-related disease in the Finnish population.

Mod Pathol 2020 04 3;33(4):551-559. Epub 2019 Nov 3.

Department of Otorhinolaryngology-Head and Neck Surgery, University of Helsinki and Helsinki University Hospital, PO Box 263, FI-00029, Helsinki, Finland.

Chronic sclerosing sialadenitis may represent one of many manifestations of an immunoglobulin G4-related disease. However, existing studies typically consist of small patient cohorts rarely conducted in Western populations. The clinical behavior of chronic sclerosing sialadenitis, including follow-up data, warrants further study. Thus, we aimed to determine whether chronic sclerosing sialadenitis always presents as IgG4-related disease or associates with autoimmune diseases and to determine which additional examinations patients may require. Between 2000 and 2017, 51 patients undergoing submandibular gland resection within the Helsinki University Hospital area were diagnosed with chronic sclerosing sialadenitis. We re-evaluated all specimens and performed immunostaining for IgG4. IgG and CD31 stainings were performed for IgG4-positive specimens. IgG4-related disease diagnosis was defined by the Boston consensus statement criteria. We revised clinical data, distributing a follow-up questionnaire to patients to register symptoms of IgG4-related disease or autoimmune disease during follow-up. The chronic sclerosing sialadenitis criteria were fulfilled in 34 patients, whereby 17 were diagnosed as non-sclerosing chronic sialadenitis. In 19 cases, a sialolith associated with a salivary gland lesion. In total, 12 of 51 cases were recognized as IgG4-positive, while two met the criteria for IgG4-related disease. These two cases belonged to the non-sclerosing chronic sialadenitis group, and both involved other organs. The histopathological features between chronic sclerosing sialadenitis and non-sclerosing chronic sialadenitis overlapped regarding the degree of fibrosis and inflammatory infiltrates. In the Finnish population, chronic sclerosing sialadenitis of the submandibular gland does not appear to present as IgG4-related disease. Non-sclerosing chronic sialadenitis can associate with IgG4-related disease. A histopathological distinction between chronic sclerosing sialadenitis and non-sclerosing chronic sialadenitis is not always unequivocal and the presence of a sialolith does not exclude IgG4-positivity. Therefore, immunostaining for IgG4 should be performed when dense plasma cell infiltration is present in either non-sclerosing chronic sialadenitis or chronic sclerosing sialadenitis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41379-019-0395-5DOI Listing
April 2020

High levels of tissue inhibitor of metalloproteinase-1 (TIMP-1) in the serum are associated with poor prognosis in HPV-negative squamous cell oropharyngeal cancer.

Cancer Immunol Immunother 2019 Aug 25;68(8):1263-1272. Epub 2019 Jun 25.

Department of Otorhinolaryngology-Head and Neck Surgery, University of Helsinki and HUS Helsinki University Hospital, P.O.Box 263, 00029 HUS, Helsinki, Finland.

Background: An emerging subset of oropharyngeal squamous cell carcinomas (OPSCC) is caused by HPV. HPV-positive OPSCC has a better prognosis than HPV-negative OPSCC, but other prognostic markers for these two different diseases are scarce. Our aim was to evaluate serum levels and tumor expression of matrix metalloproteinase-8 (MMP-8) and tissue inhibitor of metalloproteinase-1 (TIMP-1) and to assess their prognostic role in HPV-positive and HPV-negative OPSCC.

Materials And Methods: A total of 90 consecutive OPSCC patients diagnosed and treated with curative intent at the Helsinki University Hospital between 2012 and 2016 were included. Serum samples were prospectively collected. An immunofluorometric assay and an enzyme-linked immunosorbent assay were used to determine MMP-8 and TIMP-1 serum concentrations, respectively. HPV status of the tumors was determined using a combination of HPV-DNA genotyping and p16-INK4a immunohistochemistry. The endpoints were overall survival (OS) and disease-free survival (DFS).

Results: High TIMP-1 serum levels were strongly and independently associated with poorer OS (adjusted HR 14.7, 95% CI 1.8-117.4, p = 0.011) and DFS (adjusted HR 8.7, 95% CI 1.3-57.1, p = 0.024) among HPV-negative patients; this association was not observed in HPV-positive OPSCC. Although TIMP-1 was immunoexpressed in the majority of the tumor tissue samples, the level of immunoexpression was not associated with prognosis, nor did MMP-8 serum levels.

Conclusion: Our results indicate that serum TIMP-1 levels may serve as an independent prognostic marker for HPV-negative OPSCC patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00262-019-02362-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6682571PMC
August 2019

In situ hybridization for high-risk HPV E6/E7 mRNA is a superior method for detecting transcriptionally active HPV in oropharyngeal cancer.

Hum Pathol 2019 08 21;90:97-105. Epub 2019 May 21.

Department of Pathology, University of Helsinki and HUS Helsinki University Hospital, P.O.Box 21, FI-00014 HUS, Helsinki, Finland; Research Programs Unit, Translational Cancer Biology, University of Helsinki, P.O.Box 63, FI-00014, Helsinki, Finland.

Current human papillomavirus (HPV) detection methods in oropharyngeal squamous cell carcinoma (OPSCC) have varying sensitivity and specificity. We aimed to compare different HPV-detection methods against the test used in clinical practice, ie, p16 immunohistochemistry (IHC) and to evaluate whether another HPV-detection test additional to p16 IHC would be worthwhile in OPSCC specimens. The study cohort comprised 357 consecutive OPSCC patients during two time periods: 2000-2009 and 2012-2016. From tumor tissue slides, HPV mRNA via in situ hybridization (ISH), HPV DNA via ISH and HPV DNA via polymerase chain reaction (PCR) were detected. The results of these methods were compared with p16 IHC results. Additionally, clinicopathological factors were compared with the methods studied. The sensitivity of HPV mRNA ISH, HPV DNA ISH and HPV DNA PCR were 93.4%, 86.3%, and 83.5%, respectively. The corresponding specificity was 92.4%, 95.3%, and 89.1%, respectively. The negative predictive value for p16 IHC was highest (89.0%) when using mRNA ISH, and followed by DNA ISH (83.5%). ISH for high-risk HPV E6/E7 mRNA was found to be a highly specific and sensitive method for detecting HPV in OPSCC. As p16 protein may be overexpressed due to HPV-independent mechanisms, all p16 IHC-positive OPSCCs should be considered for retesting using mRNA ISH in order to verify transcriptionally active HPV. This is especially critical when considering de-escalated treatment approaches for patients with HPV-positive tumors and still maintaining favorable outcomes for this subgroup of patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.humpath.2019.05.006DOI Listing
August 2019

Tumor volume as a prognostic marker in p16-positive and p16-negative oropharyngeal cancer patients treated with definitive intensity-modulated radiotherapy.

Strahlenther Onkol 2018 08 17;194(8):759-770. Epub 2018 May 17.

Department of Otorhinolaryngology-Head and Neck Surgery, University of Helsinki and Helsinki University Hospital, Kasarmikatu 11-13, 00029 HUS, Helsinki, Finland.

Purpose: To investigate the impact of primary gross tumor volume (pGTV) and nodal gross tumor volume (nGTV) in oropharyngeal squamous cell carcinoma (OPSCC) and the difference in their role between human papillomavirus (HPV)-positive and HPV-negative patients.

Methods: The patient cohort consists of 91 OPSCC patients treated with definitive radiochemotherapy or radiotherapy using intensity-modulated radiotherapy (IMRT). All patients had a minimum follow-up of 31 months. Volume measurements were made from computer tomography (CT) scans and HPV status was assessed by p16 immunohistochemistry. The end points were as follows: overall survival (OS), disease-free survival (DFS) and locoregional control (LRC).

Results: pGTV was a significant independent prognostic factor for overall survival (OS; p = 0.020) in p16-negative patients. nGTV of p16-negative tumors had significant prognostic value in all end points in multivariate analyses. High-stage (III-IVc) p16-negative tumors were only associated with significantly poorer OS (p = 0.046) but not with poorer LRC or DFS when compared with the low-stage (I-II) tumors. nGTV of p16-positive tumors was an independent prognostic factor for DFS (p = 0.005) and LRC (p = 0.007) in multivariate analyses.

Conclusion: pGTV may serve as an independent prognostic factor in p16-negative patients and nGTV may serve as an independent prognostic factor both in p16-positive and p16-negative patients treated with radiochemotherapy or radiotherapy using IMRT. Tumor volume may have an impact on selecting patients for de-escalation protocols in the future, both in p16-positive and p16-negative patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00066-018-1309-zDOI Listing
August 2018

Presenting symptoms and clinical findings in HPV-positive and HPV-negative oropharyngeal cancer patients.

Acta Otolaryngol 2018 05 21;138(5):513-518. Epub 2017 Nov 21.

a Department of Otorhinolaryngology - Head and Neck Surgery , University of Helsinki and Helsinki University Hospital , Helsinki , Finland.

Objectives: Oropharyngeal squamous cell carcinoma (OPSCC) is divided in two different disease entities depending on HPV involvement. We investigated differences in presenting symptoms and clinical findings in patients with HPV-positive and -negative OPSCC tumors.

Methods: Altogether 118 consecutive patients diagnosed with primary OPSCC between 2012 and 2014 at the Helsinki University Hospital were included. HPV-status of the tumors was assessed by PCR detection of HPV DNA and immunostaining with p16-INK4a antibody.

Results: Fifty-one (47.7%) of the patients had HPV-positive and 56 (52.3%) HPV-negative tumors. Forty-nine (49/51, 96.1%) of the HPV+ tumors were also p16+ showing high concordance. The most common presenting symptom among HPV+/p16+ patients was a neck mass (53.1%), whereas any sort of pain in the head and neck area was more frequently related to the HPV-/p16- (60.0%) group. HPV+/p16+ tumors had a tendency to locate in the tonsillar complex and more likely had already spread into regional lymph nodes compared with HPV-/p16- tumors. Smoking and heavy alcohol consumption were significantly more common among HPV−/p16− patients but also rather common among HPV+/p16+ patients [corrected].

Conclusions: This analysis of symptoms and signs confirm that OPSCC can be dichotomized in two distinct disease entities as defined by HPV status.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/00016489.2017.1405279DOI Listing
May 2018

Submandibular gland cancer: Specific features and treatment considerations.

Head Neck 2018 Jan 30;40(1):154-162. Epub 2017 Oct 30.

Department of Otorhinolaryngology - Head and Neck Surgery, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.

Background: In the absence of unified treatment protocol, we evaluated the management and outcomes of submandibular gland cancers in an unselected patient series.

Methods: We included all patients with resected submandibular gland cancer treated at the Helsinki University Hospital from 2000 to 2010 with a 5-year minimum follow-up.

Results: Twenty-five patients with cancer represented 30% of submandibular gland neoplasms, and most were adenoid cystic carcinomas (ACCs; 56%). At presentation, 3 patients showed clinical signs of probable malignancy. Of 22 neck dissection specimens, 5 patients (20%) had metastases with an occult metastasis rate of 4%. Cancer recurred in 11 patients (44%), of which 7 (28%) were only at a distant site. The 5-year disease-specific survival (DSS) and overall survival (OS) rates were 76%, and disease-free survival (DFS) was 68%.

Conclusion: Most tumors were ACCs differing from the histological pattern of parotid gland cancers. Occult metastases were rare. The rarity of submandibular gland cancer, its variable histological pattern, and varying biological behavior warrant centralized management.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/hed.24981DOI Listing
January 2018

WRAP53β, survivin and p16INK4a expression as potential predictors of radiotherapy/chemoradiotherapy response in T2N0-T3N0 glottic laryngeal cancer.

Oncol Rep 2017 Oct 11;38(4):2062-2068. Epub 2017 Aug 11.

Division of Otorhinolaryngology and Head and Neck Surgery, Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.

The current treatment recommendation for T2-3N0M0 glottic squamous cell carcinoma (SCC) in the Nordic countries comprises of radiotherapy (RT) and chemoradiotherapy (CRT). Tumor radiosensitivity varies and another option is primary surgical treatment, which underlines the need for predictive markers in this patient population. The aim of the present study was to investigate the relation of the proteins WRAP53β, survivin and p16INK4a to RT/CRT response and ultimate outcome of patients with T2-T3N0 glottic SCC. Protein expression was determined using immunohistochemistry on tumors from 149 patients consecutively treated with RT or CRT at Helsinki University Hospital, Karolinska University Hospital, and Linköping University Hospital during 1999-2010. Our results demonstrate a significantly better 5-year relapse-free survival, disease-free survival (DFS), disease-specific survival and overall survival of patients with T3N0 tumors treated with CRT compared with RT alone. Patients with tumors showing a cytoplasmic staining of WRAP53β revealed significantly worse DFS compared with those with nuclear staining. For survivin, we observed a trend towards better 5-year DFS in patients with strong nuclear survivin expression compared with those with weak nuclear survivin expression (p=0.091). Eleven (7%) tumors showed p16 positivity, with predilection to younger patients, and this age group of patients with p16-positive SCC had a significantly better DFS compared with patients with p16-negative SCC. Taken together, our results highlight WRAP53β as a potential biomarker for predicting RT/CRT response in T2-T3N0 glottic SCC. p16 may identify a small but distinct group of glottic SCC with favorable outcome. Furthermore, for T3N0 patients better outcome was observed following CRT compared to RT alone.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3892/or.2017.5898DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5652956PMC
October 2017

Preoperative evaluation and surgical planning of submandibular gland tumors.

Head Neck 2017 06 28;39(6):1071-1077. Epub 2017 Mar 28.

Department of Otorhinolaryngology - Head and Neck Surgery, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.

Background: Roughly half of submandibular gland neoplasms are malignant. Because preoperative information on the nature of these tumors remains limited, both preoperative evaluation and assessment of the extent of primary surgery warrant guidelines that are more accurate.

Methods: We evaluated the preoperative examinations and management of all submandibular gland neoplasms treated surgically at the Helsinki University Hospital between 2000 and 2010.

Results: Of the 83 tumors, 58 (70%) were benign and 25 (30%) were malignant. Of the benign tumors, 54 (93%) were pleomorphic adenomas. The cytology in 8 patients (10%) was class IV or V, and in 12 patients was class III; the tumors in 9 of these 12 patients turned out to be malignant. Of all malignancies, 10 (40%) required additional more extensive surgery.

Conclusion: Ultrasound-guided fine-needle aspiration cytology (FNAC) proved useful, with limitations, in preoperative examination. Surgeons should always obtain wide margins whenever possible, even when clinical means or cytology indicates no malignancy. © 2017 Wiley Periodicals, Inc. Head Neck 39: 1071-1077, 2017.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/hed.24691DOI Listing
June 2017

Multidisciplinary Approach to Management of Temporal Bone Giant Cell Tumor.

J Neurol Surg Rep 2016 Jul;77(3):e144-e149

Department of Otorhinolaryngology-Head and Neck Surgery, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.

 Giant cell tumors (GCTs) are rare osseous tumors that rarely appear in the skull.  We review the clinical course of a 28-year-old previously healthy woman with a complicated GCT.  The reviewed patient presented with a middle cranial fossa tumor acutely complicated by reactive mastoiditis. Left tympanomastoidectomy was performed for drainage of the mastoiditis and for biopsies of the tumor. Due to the challenging tumor location, the patient was treated with denosumab, a fully humanized monoclonal antibody against receptor activator of nuclear factor kappa-B ligand, for 7 months, which resulted in significant preoperative tumor shrinkage. Extensive temporal craniotomy and resection of the tumor followed utilizing a temporomandibular joint total endoprosthesis for reconstruction. A recurrence of the tumor was detected on computed tomography at 19 months after surgery and treated with transtemporal tumor resection, parotidectomy, and mandible re-reconstruction.  A multidisciplinary approach resulted in a good functional result and, finally, an eradication of the challengingly located middle cranial fossa tumor.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1055/s-0036-1592082DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5045306PMC
July 2016

[Neck lump--fine-needle aspiration biopsy specimen in diagnostics and planning of therapy].

Duodecim 2014 ;130(22-23):2405-12

HYKS, korva-, nenä- ja kurkkutautien klinikka.

In elucidating the cause of a non-tender neck lump, the age of the patient, location and finding on palpation of lumps, and clinical examination of ear, nose and throat disorders and possible other findings are crucial. Fine-needle aspiration biopsy specimen, most commonly obtained in connection with ultrasonic imaging, is a key method in diagnosing lumps of the neck and salivary gland region that are obviously noninflammatory. Ultrasonic imaging combined with a cytological specimen is primary in the case of otherwise normal clinical examination.
View Article and Find Full Text PDF

Download full-text PDF

Source
January 2015

Identification and validation of human papillomavirus encoded microRNAs.

PLoS One 2013 30;8(7):e70202. Epub 2013 Jul 30.

Institute of Biotechnology, University of Helsinki, Helsinki, Finland.

We report here identification and validation of the first papillomavirus encoded microRNAs expressed in human cervical lesions and cell lines. We established small RNA libraries from ten human papillomavirus associated cervical lesions including cancer and two human papillomavirus harboring cell lines. These libraries were sequenced using SOLiD 4 technology. We used the sequencing data to predict putative viral microRNAs and discovered nine putative papillomavirus encoded microRNAs. Validation was performed for five candidates, four of which were successfully validated by qPCR from cervical tissue samples and cell lines: two were encoded by HPV 16, one by HPV 38 and one by HPV 68. The expression of HPV 16 microRNAs was further confirmed by in situ hybridization, and colocalization with p16INK4A was established. Prediction of cellular target genes of HPV 16 encoded microRNAs suggests that they may play a role in cell cycle, immune functions, cell adhesion and migration, development, and cancer. Two putative viral target sites for the two validated HPV 16 miRNAs were mapped to the E5 gene, one in the E1 gene, two in the L1 gene and one in the LCR region. This is the first report to show that papillomaviruses encode their own microRNA species. Importantly, microRNAs were found in libraries established from human cervical disease and carcinoma cell lines, and their expression was confirmed in additional tissue samples. To our knowledge, this is also the first paper to use in situ hybridization to show the expression of a viral microRNA in human tissue.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0070202PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3728184PMC
April 2014

Detection rates of precancerous and cancerous cervical lesions within one screening round of primary human papillomavirus DNA testing: prospective randomised trial in Finland.

BMJ 2012 Nov 29;345:e7789. Epub 2012 Nov 29.

Mass Screening Registry, Finnish Cancer Registry, FI-00130 Helsinki, Finland.

Objective: To compare the detection rates of precancerous and cancerous cervical lesions by human papillomavirus (HPV) DNA testing and by conventional cytology screening.

Design: Prospective randomised trial. Two cohorts were followed over one screening round of five years, screened initially by primary HPV DNA testing or by primary Pap test.

Setting: Population based programme for cervical cancer screening in Finland.

Participants: Women aged 25-65 years invited for screening in 2003-07 (101,678 in HPV arm; 101,747 in conventional cytology arm).

Intervention: Women were randomly allocated (1:1) to primary HPV DNA screening followed by cytology triage if they had positive results, or to primary cytology screening. Screening method was disclosed at the screening visit. Trial personnel involved were aware of all test results.

Main Outcome Measures: Cumulative detection rates of cervical intraepithelial neoplasia (CIN), adenocarcinoma in situ (AIS), and invasive cervical cancer before the second screening (after five years) or before 31 December 2008. Lesions detected at screening and during the five year interval were included.

Results: 1010 and 701 precancerous or cancerous lesions were detected during an average follow-up of 3.6 years in the HPV and cytology arms, respectively. Among invited women, the hazard ratio was 1.53 (95% confidence interval l.28 to 1.84) for CIN grade 1, 1.54 (1.33 to 1.78) for CIN 2, 1.32 (1.09 to 1.59) for CIN 3 or AIS, and 0.81 (0.48 to 1.37) for cervical cancer. In 25-34 year old participants, the cumulative hazard (or cumulative detection rate) was 0.0057 (0.0045 to 0.0072) for HPV screening versus 0.0046 (0.0035 to 0.0059) for conventional screening; corresponding data for women aged 35 years and older were 0.0022 (0.0019 to 0.0026) and 0.0017 (0.0014 to 0.0021), respectively.

Conclusions: Primary HPV DNA screening detects more cervical lesions than primary cytology within one screening round of five years. Even if the detection rate of CIN 3 or AIS increased in the HPV arm in both age groups, the absolute difference in cumulative rates in women aged 35 years or older was small. By carefully selecting age groups and screening intervals, HPV screening could increase the overall detection rate of cervical precancerous lesions only slightly. However, these findings should be interpreted in the context of the high level of opportunistic screening that occurs in Finland.

Trial Registration: International Standard Randomised Controlled Trial ISRCTN23885553.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3509927PMC
http://dx.doi.org/10.1136/bmj.e7789DOI Listing
November 2012

The HPV test has similar sensitivity but more overdiagnosis than the Pap test--a randomised health services study on cervical cancer screening in Finland.

Int J Cancer 2013 May 12;132(9):2141-7. Epub 2012 Oct 12.

Finnish Cancer Registry, Helsinki, Finland.

We compared test sensitivity (in terms of prevented cancers) and overdiagnosis (in terms of non-progressive pre-invasive lesions) between the human papillomavirus test (HPV test, Hybrid Capture 2) and the traditional Pap test in routine screening for cervical cancer. The design was a randomised (1:1) health services study in Finland with intake between 2003 and 2007. We estimated sensitivity by the incidence method within one screening round. Overdiagnosis was based on the rate of cervical intraepithelial Grade 3 (CIN3) lesions diagnosed at screen and during the following interval. Out of 203,788 randomised women 132,298 attended (65% in both study arms) and 600,753 person-years accumulated among attenders up to the end of 2010. In all attenders, 34 invasive cervical cancers and 288 CIN3 lesions were diagnosed at screen or during the following interval. The interval cancer incidence was 2.5/10(5) person-years (sensitivity 0.87) and 1.4 (sensitivity 0.93) in the HPV arm and Pap test arm, respectively. The rate of CIN3 lesions was 57.1 and 38.8, respectively. In conclusion, sensitivity of HPV testing was similar to that of Pap testing but caused more overdiagnosis. Therefore, implementation of HPV testing needs to be reconsidered especially in countries with well organised programmes.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/ijc.27850DOI Listing
May 2013

Cell culture model predicts human disease: Altered expression of junction proteins and matrix metalloproteinases in cervical dysplasia.

BMC Clin Pathol 2012 Aug 3;12. Epub 2012 Aug 3.

Haartman Institute, Department of Virology, University of Helsinki, POB 21 (Haartmaninkatu 3), FIN-00014, Helsinki, Finland.

Background: Cervical cancer is necessarily caused by human papillomaviruses, which encode three oncogenes manifesting their functions by interfering with a number of cellular proteins and pathways: the E5, E6, and E7 proteins. We have earlier found in our microarray studies that the E5 oncogene crucially affects the expression of cellular genes involved in adhesion and motility of epithelial cells.

Methods: In order to biologically validate our previous experimental findings we performed immunohistochemical staining of a representative set of tissue samples from different grades of high-risk human papillomavirus associated cervical disease as well as normal squamous and columnar cervical epithelium. Three-dimensional collagen raft cultures established from E5-expressing and control epithelial cells were also examined. The expression of p16, matrix metalloproteinase (MMP) -7, MMP-16, cytokeratin (CK) 8/18, laminin, E-cadherin and beta-catenin was studied.

Results: In agreement with our previous microarray studies, we found intense staining for E-cadherin and beta-catenin in adherens junctions even in high-grade cervical lesions. Staining for MMP-16 was increased in severe disease as well. No significant change in staining for MMP-7 and cytokeratin 8/18 along with the grade of cervical squamous epithelial disease was observed.

Conclusions: Here we have confirmed, using tissue material from human papillomavirus associated lesions, some of the cellular gene expression modifications that we earlier reported in an experimental system studying specifically the E5 oncogene of papillomaviruses. These findings were partially surprising in the context of cervical carcinogenesis and emphasize that the complexity of carcinogenesis is not yet fully understood. Microarray approaches provide a wide overwiev of gene expression in experimental settings, which may yield biologically valid biomarkers for disease diagnostics, prognosis, and follow-up.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/1472-6890-12-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3495715PMC
August 2012

Adenoidectomy in young children and serum IgG antibodies to pneumococcal surface protein A and choline binding protein A.

Int J Pediatr Otorhinolaryngol 2012 Nov 24;76(11):1569-74. Epub 2012 Jul 24.

Department of Otorhinolaryngology, Helsinki University Central Hospital, Finland.

Objective: We have previously reported that surgical removal of the nasopharyngeal adenoid in young children resulted in increased risk of nasopharyngeal colonization by pneumococci. We now investigated whether adenoidectomy influences the development of serum IgG antibodies to pneumococcal choline-binding protein A (CbpA) and pneumococcal surface protein A (PspA).

Methods: Altogether 217 children aged 12-48 months who had recurrent or persistent otitis media were randomized to undergo or not to undergo adenoidectomy. All the children underwent insertion of tympanostomy tubes. 166 children were followed-up for 3 years. The main outcome measures were concentrations of serum IgG antibodies to CbpA and PspA three years after randomization. Nasopharyngeal colonization by pneumococci was assessed 1, 2, and 3 years after randomization.

Results: Adenoidectomy decreased concentrations of CbpA antibodies by ca. 25% independently of the observed increase in pneumococcal carriage (OR of log(10) transformed concentrations 0.74, 95% CI 0.58-0.94, P=0.016). Concentrations of PspA antibodies were lower and they seemed not to be influenced by adenoidectomy.

Conclusions: Adenoidectomy in young children causes a small but detectable impairment in the development of serum IgG antibodies to pneumococcal CbpA. The adenoid seems to have a role in augmenting systemic immunity against pneumococci.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ijporl.2012.07.013DOI Listing
November 2012

Detection of human papillomaviruses by polymerase chain reaction and ligation reaction on universal microarray.

PLoS One 2012 23;7(3):e34211. Epub 2012 Mar 23.

Institute of Biotechnology, University of Helsinki, Helsinki, Finland.

Sensitive and specific detection of human papillomaviruses (HPV) in cervical samples is a useful tool for the early diagnosis of epithelial neoplasia and anogenital lesions. Recent studies support the feasibility of HPV DNA testing instead of cytology (Pap smear) as a primary test in population screening for cervical cancer. This is likely to be an option in the near future in many countries, and it would increase the efficiency of screening for cervical abnormalities. We present here a microarray test for the detection and typing of 15 most important high-risk HPV types and two low risk types. The method is based on type specific multiplex PCR amplification of the L1 viral genomic region followed by ligation detection reaction where two specific ssDNA probes, one containing a fluorescent label and the other a flanking ZipCode sequence, are joined by enzymatic ligation in the presence of the correct HPV PCR product. Human beta-globin is amplified in the same reaction to control for sample quality and adequacy. The genotyping capacity of our approach was evaluated against Linear Array test using cervical samples collected in transport medium. Altogether 14 out of 15 valid samples (93%) gave concordant results between our test and Linear Array. One sample was HPV56 positive in our test and high-risk positive in Hybrid Capture 2 but remained negative in Linear Array. The preliminary results suggest that our test has accurate multiple HPV genotyping capability with the additional advantages of generic detection format, and potential for high-throughput screening.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0034211PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3311614PMC
August 2012

Exome sequencing reveals germline NPAT mutation as a candidate risk factor for Hodgkin lymphoma.

Blood 2011 Jul 11;118(3):493-8. Epub 2011 May 11.

Department of Medical Genetics, University of Helsinki, Helsinki, Finland.

A strong clustering of Hodgkin lymphoma in certain families has been long acknowledged. However, the genetic factors in the background of familial Hodgkin lymphoma are largely unknown. We have studied a family of 4 cousins with a rare subtype of the disease, nodular lymphocyte predominant Hodgkin lymphoma. We applied exome sequencing together with genome-wide linkage analysis to this family and identified a truncating germline mutation in nuclear protein, ataxia-telangiectasia locus (NPAT) gene, which segregated in the family. We also studied a large number of samples from other patients with Hodgkin lymphoma, and a germline variation leading to the deletion of serine 724 was found in several cases suggesting an elevated risk for the disease (odds ratio = 4.11; P = .018). NPAT is thus far the first gene implicated in nodular lymphocyte predominant Hodgkin lymphoma predisposition.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1182/blood-2011-03-341560DOI Listing
July 2011

Adenoidectomy and nasopharyngeal carriage of Streptococcus pneumoniae in young children.

Arch Dis Child 2010 Sep 26;95(9):696-702. Epub 2010 May 26.

Department of Otorhinolaryngology, Helsinki University Central Hospital, Finland.

Objective: The effect of adenoidectomy on nasopharyngeal colonisation of pathogens has not previously been evaluated. The authors studied the effect of adenoidectomy on nasopharyngeal colonisation by bacteria causing otitis media and the effect of adenoidectomy on the development of pneumococcal capsular polysaccharide antibodies.

Design: Randomised controlled study.

Setting: Tertiary care centre.

Patients: 217 children aged 12-48 months who had recurrent or persistent otitis media were randomised. 166 children were followed up for 3 years.

Intervention: Random allocation to undergo adenoidectomy or not to undergo adenoidectomy. All the children underwent insertion of tympanostomy tubes.

Main Outcome Measures: Nasopharyngeal colonisation by pneumococci, Haemophilus influenzae and Moraxella catarrhalis 1, 2 and 3 years after randomisation. Serum IgG antibodies against pneumococcal capsular polysaccharide serotypes 6B, 14, 19F and 23F 3 years after randomisation.

Results: After the first year of randomisation adenoidectomy increased nasopharyngeal carriage of pneumococci (RR, 1.47; 95% CI 1.04 to 2.07) but it did not influence the carriage of H influenzae or M catarrhalis. Among carriers of serotype 6B pneumococci, adenoidectomy resulted in lower concentrations of pneumococcal serotype 6B polysaccharide antibodies (ratio of geometric means of antibody concentrations, 0.37; 95% CI 0.16 to 0.85). Concentrations of serotype 14, 19F and 23F antibodies seemed not to be influenced by adenoidectomy. Despite this, adenoidectomy resulted in a significant increase in nasopharyngeal carriage of serotype 19F pneumococci.

Conclusions: Adenoidectomy increases the risk of nasopharyngeal carriage of pneumococci in children younger than 4 years of age. This may be independent of the development of serum IgG capsular polysaccharide antibodies.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1136/adc.2009.165654DOI Listing
September 2010

Rate of cervical cancer, severe intraepithelial neoplasia, and adenocarcinoma in situ in primary HPV DNA screening with cytology triage: randomised study within organised screening programme.

BMJ 2010 Apr 27;340:c1804. Epub 2010 Apr 27.

Mass Screening Registry of the Finnish Cancer Registry, Pieni Roobertinkatu 9, FIN-00130 Helsinki, Finland.

Objective: To assess the performance and impact of primary human papillomavirus (HPV) DNA screening with cytology triage compared with conventional cytology on cervical cancer and severe pre-cancerous lesions.

Design: Randomised trial.

Setting: Population based screening programme for cervical cancer in southern Finland in 2003-5.

Participants: 58 076 women, aged 30-60, invited to the routine population based screening programme for cervical cancer.

Interventions: Primary HPV DNA test (hybrid capture II) with cytology triage if the result was positive or conventional cytological screening (reference).

Main Outcome Measures: Rate of cervical cancer, cervical intraepithelial neoplasia (CIN) grade III, and adenocarcinoma in situ (as a composite outcome referred to as CIN III+) during 2003-7 through record linkage between files from the screening registry and the national cancer registry.

Results: In the HPV and conventional arms there were 95 600 and 95 700 woman years of follow-up and 76 and 53 cases of CIN III+, respectively (of which six and eight were cervical cancers). The relative rate of CIN III+ in the HPV arm versus the conventional arm was 1.44 (95% confidence interval 1.01 to 2.05) among all women invited for screening and 1.77 (1.16 to 2.74) among those who attended. Among women with a normal or negative test result, the relative rate of subsequent CIN III+ was 0.28 (0.04 to 1.17). The rate of cervical cancer between arms was 0.75 (0.25 to 2.16) among women invited for screening and 1.98 (0.52 to 9.38) among those who attended.

Conclusions: When incorporated into a well established organised screening programme, primary HPV screening with cytology triage was more sensitive than conventional cytology in detecting CIN III+ lesions. The number of cases of cervical cancer was small, but considering the high probability of progression of CIN III the findings are of importance regarding cancer prevention.

Trial Registration: Current Controlled Trials ISRCTN23885553.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3191726PMC
http://dx.doi.org/10.1136/bmj.c1804DOI Listing
April 2010

Plasma level of tissue inhibitor of matrix metalloproteinase-1 but not that of matrix metalloproteinase-8 predicts survival in head and neck squamous cell cancer.

Oral Oncol 2010 Jul 3;46(7):514-8. Epub 2010 Apr 3.

Department of Oral and Maxillofacial Diseases, Institute of Dentistry, University of Helsinki and Helsinki University Central Hospital, Helsinki, Finland.

Expression of matrix metalloproteinase-8 (MMP-8) in tongue cancer cells has been associated with an improved prognosis. MMP-8 is inhibited by tissue inhibitor of matrix metalloproteinase-1 (TIMP-1) and elevated levels of TIMP-1 in blood have been associated with poor prognosis in many cancers. We wished to evaluate the usefulness of peripheral blood MMP-8 and TIMP-1 levels as well as the genotypes of MMP8 and TIMP1 in predicting prognosis in head and neck squamous cell carcinoma (HNSCC). Plasma concentrations of MMP-8 and TIMP-1 were analyzed in 136 HNSCC patients. MMP8 and TIMP1 genotypes were determined by analysis of single nucleotide polymorphisms (SNP) in peripheral blood DNA. The mean follow-up time was 3.3years. We found that plasma MMP-8 level did not predict survival but that TIMP-1 level was associated with survival. The adjusted hazard ratio of death scored as a continuous variable on the log(10) scale was 23.2 (95% CI 1.88-286, P=0.01) and that of MMP-8 1.24 (95% CI 0.54-2.84, P=0.61). Immunohistochemical staining showed that TIMP-1 was expressed in vascular endothelium of tumor. TIMP-1 levels were associated with TIMP1 genotype in women but not in men. MMP8 genotype did not correlate with survival or MMP-8 level. Plasma TIMP-1 levels predict survival in HNSCC. TIMP-1 expression is genetically controlled in women. As TIMP-1 inhibits the activity of MMP-8 and it also functions as a growth factor, it may directly influence HNSCC progression.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.oraloncology.2010.03.002DOI Listing
July 2010

Acquired jugular vein aneurysm.

Int J Otolaryngol 2009 25;2009:535617. Epub 2009 Feb 25.

Department of Otorhinolaryngology, Kymenlaakso Central Hospital, 48210 Kotka, Finland.

Venous malformations of the jugular veins are rare findings. Aneurysms and phlebectasias are the lesions most often reported. We report on an adult patient with an abruptly appearing large tumorous mass on the left side of the neck identified as a jugular vein aneurysm. Upon clinical examination with ultrasound, a lateral neck cyst was primarily suspected. Surgery revealed a saccular aneurysm in intimate connection with the internal jugular vein. Histology showed an organized hematoma inside the aneurysmal sac, which had a focally thinned muscular layer. The terminology and the treatment guidelines of venous dilatation lesions are discussed. For phlebectasias, conservative treatment is usually recommended, whereas for saccular aneurysms, surgical resection is the treatment of choice. While an exact classification based on etiology and pathophysiology is not possible, a more uniform taxonomy would clarify the guidelines for different therapeutic modalities for venous dilatation lesions.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1155/2009/535617DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2809428PMC
July 2011

Age-specific evaluation of primary human papillomavirus screening vs conventional cytology in a randomized setting.

J Natl Cancer Inst 2009 Dec 9;101(23):1612-23. Epub 2009 Nov 9.

Mass Screening Registry, Finnish Cancer Registry, Pieni Roobertinkatu 9, FI-00130 Helsinki, Finland.

Background: Human papillomavirus (HPV) DNA testing has shown higher sensitivity than cytology for detecting cervical lesions, but it is uncertain whether the higher sensitivity is dependent on the age of the woman being screened. We compared the age-specific performance of primary HPV DNA screening with that of conventional cytology screening in the setting of an organized population-based cervical cancer screening program in Finland.

Methods: From January 1, 2003, to December 31, 2005, randomized invitations were sent to women aged 25-65 years for routine cervical cancer screening by primary high-risk HPV DNA testing (n = 54 207) with a Hybrid Capture 2 assay followed by cytology triage for women who were HPV DNA positive or by conventional cytology screening (n = 54 218). In both screening arms, cytology results of low-grade squamous intraepithelial lesion or worse triggered a referral for colposcopy. Relative rates (RRs) of detection to assess test sensitivity, specificity, and positive predictive values (PPVs) with 95% confidence intervals (CIs) were calculated for the histological endpoints of cervical intraepithelial neoplasia (CIN) grade 1 or higher (CIN 1+), CIN grade 2 or higher (CIN 2+), and CIN grade 3 or higher (CIN 3+). All statistical tests were two-sided.

Results: The overall frequency of colposcopy referrals was 1.2% in both screening arms. Women younger than 35 years were referred more often in the HPV DNA screening vs the conventional screening arm (RR = 1.27, 95% CI = 1.01 to 1.60). The prevalence of histologically confirmed CIN or cancer was 0.59% in the HPV DNA screening arm vs 0.43% in the conventional screening arm. The relative rates of detection for CIN 1, CIN 2, and CIN 3+ for HPV DNA screening with cytology triage vs conventional screening were 1.44 (95% CI = 0.99 to 2.10), 1.39 (95% CI = 1.03 to 1.88), and 1.22 (95% CI = 0.78 to 1.92), respectively. The specificity of the HPV DNA test with cytology triage was equal to that of conventional screening for all age groups (99.2% vs 99.1% for CIN 2+, P = .13). Among women aged 35 years or older, the HPV DNA test with cytology triage tended to have higher specificity than conventional screening. The PPVs for HPV DNA screening with cytology triage were consistently higher than those for conventional screening. In both screening arms, the test specificities increased with increasing age of the women being screening, whereas the highest PPVs were observed among the youngest women being screened. Overall, 7.2% of women in the HPV DNA screening arm vs 6.6% of women in the conventional screening arm were recommended for intensified follow-up, and the percentages were highest among 25- to 29-year-olds (21.9% vs 10.0%, respectively).

Conclusions: Primary HPV DNA screening with cytology triage is more sensitive than conventional screening. Among women aged 35 years or older, primary HPV DNA screening with cytology triage is also more specific than conventional screening and decreases colposcopy referrals and follow-up tests.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/jnci/djp367DOI Listing
December 2009

Test positivity cutoff level of a high risk human papillomavirus test could be increased in routine cervical cancer screening.

Int J Cancer 2008 Dec;123(12):2902-6

Mass Screening Registry, Finnish Cancer Registry, Helsinki, Finland.

We present data on test positivity, relative sensitivity, rates of detection and relative specificity for primary human papillomavirus (HPV) testing with different cutoff levels for test positivity, in comparison to conventional cytology. In 2003-2004, 18,438 women were screened primarily with Hybrid Capture 2 (HC 2) assay, a test for oncogenic HPV DNA, and 21,446 with conventional cytology within the organised screening programme in Finland. A cytological triage test was performed for the HPV positives. Women with cytology equal to low grade squamous intraepithelial lesion (LSIL) or worse were referred for colposcopy. The relative sensitivity measured as relative risk (RR) of any cervical intraepithelial neoplasia (CIN) or cancer was 1.58 for the HPV test at the relative light units (rlu) ratio cutoff 1.00, in comparison to cytology. With the cutoff 3.00, all CIN 2+ lesions were detected. With cutoff 10.00, 2 of the 22 CIN 3+ lesions were missed. Relative specificity for HPV screening for any CIN was 92.6% at cutoff 1.00, 94.6% at cutoff 3.00 and 96.3% at cutoff 10.00. For CIN 3+ specificity estimates for these cutoffs were 92.1%, 94.1% and 95.8%, respectively. Used for routine screening as the sole test, the HPV test cutoff can be increased from the level recommended for clinical use. With HC 2, the detection rate at rlu ratio cutoff 10.00 is still at the level of high-quality conventional screening. At that level, the false positive rate is reduced by about half and the specificity of the HPV test becomes equal to the average specificity of conventional cytology.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/ijc.23839DOI Listing
December 2008

Prevalence of oncogenic human papillomavirus infection in an organised screening population in Finland.

Int J Cancer 2008 Sep;123(6):1344-9

Mass Screening Registry, Finnish Cancer Registry, Pieni Roobertinkatu 9, FI-00130 Helsinki, Finland.

A persistent high-risk human papillomavirus (hrHPV) infection is a necessary condition for developing a cervical intraepithelial neoplasia and cervical cancer. The viral aetiology in cervical carcinogenesis has stimulated attempts to use HPV DNA detection in cervical cancer screening. In Finland there is an ongoing study assessing the benefits of primary HPV DNA testing in the setting of centrally organised mass screening for cervical cancer. Here we present the age-specific prevalence of hrHPV infection and associated sociodemographic factors of 16,895 women aged 25-65 years attending the 5-yearly cervical cancer screening between years 2003 and 2004. The overall hrHPV prevalence rate was 7.5%. The peak prevalence at the age group of 25-29 was 24.1% decreasing steadily thereafter to approximately 2.9% in women aged 65 years. Young age and marital status were the main determinants for oncogenic HPV types. Our study confirms the inverse relationship between age and hrHPV prevalence reported in many developed countries. As our prevalence rates and hence background risk for cervical cancer are not lower than in other European countries, it is likely that our lowest cervical cancer burden in Europe is due to health care actions justifying the organised cervical cancer screening.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/ijc.23670DOI Listing
September 2008

Screening with a primary human papillomavirus test does not increase detection of cervical cancer and intraepithelial neoplasia 3.

Eur J Cancer 2008 Mar 8;44(4):565-71. Epub 2008 Jan 8.

Mass Screening Registry, Finnish Cancer Registry, Liisankatu 21 B, FI-00170 Helsinki, Finland.

Aim: To determine cross-sectional validity of primary human papillomavirus (HPV) screening in comparison to cytological screening.

Methods: During 2003-2004, 61,149 women were individually randomised to screening with a test for oncogenic HPV DNA or to conventional cytological screening within the Finnish cervical screening programme.

Results: For HPV screening, cross-sectional relative sensitivity for cervical intraepithelial neoplasia (CIN) or cancer was 1.58 (95 % confidence interval 1.19-2.09) in comparison to cytology. At the level of CIN 3 or cancer no increase in relative sensitivity was observed. Cross-sectional specificity estimates for the screening arms were comparable, but the specificity of screening with sole HPV DNA test was clearly inferior.

Conclusions: Primary HPV screening with cytology triage finds more CIN lesions compared to conventional screening but mild lesions are overrepresented. This is likely to result in overdiagnosis since most mild lesions are regressive.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ejca.2007.12.002DOI Listing
March 2008

The prognostic role of blood lymphocyte subset distribution in patients with resected high-risk primary or regionally metastatic melanoma.

J Immunother 2007 Oct;30(7):773-9

Department of Oncology, HUSLAB, Helsinki University Central Hospital, Finland.

The aim of this study was to investigate whether the profile of peripheral blood lymphocyte subsets of patients with high-risk malignant melanoma is associated with prognosis. Blood samples were systematically obtained from 31 patients with high-risk melanoma eligible for the Nordic Melanoma Cooperative Group adjuvant interferon study. The frequencies of peripheral blood lymphocyte subsets were monitored by flow cytometry using CD3, CD4, CD8, CD56, and CD69 monoclonal antibodies. Patients with low proportions of CD3+CD4+CD69+ cells and of CD3+CD56+ cells before treatment had an improved disease-free survival compared to those with high proportions [77.7 vs. 16.8 mo, hazard ratio (HR) 0.25, confidence interval (CI) 0.09-0.71, P=0.005 and 77.2 vs. 16.0 mo, HR: 0.25, CI 0.086-0.73, P=0.001, respectively]. Low pretreatment levels of these cell populations also correlated with a better overall survival (79.2 vs. 22.6 mo, HR: 0.17, CI 0.05-0.52, P=0.0005 and 78.2 vs. 21.4 mo, HR: 0.2, CI 0.07-0.59, P=0.001, respectively). In the multivariate analysis both the pretreatment proportion of CD3+CD4+CD69+ cells (P=0.01, HR: 0.21, CI 0.07-0.67) and CD3+CD56+ cells (P=0.01, HR: 0.22, CI 0.062-0.65) were independent prognostic factors for overall survival. Our data show that both the proportions of CD3+CD4+CD69+ cells and of CD3+CD56+ cells seem to have a prognostic potential in the natural course of melanoma. These results need to be confirmed in larger studies.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/CJI.0b013e31814e0898DOI Listing
October 2007

Passive smoking after tympanostomy and risk of recurrent acute otitis media.

Int J Pediatr Otorhinolaryngol 2007 Aug 19;71(8):1305-10. Epub 2007 Jun 19.

Department of Otorhinolaryngology, Helsinki University Central Hospital, Helsinki, Finland.

Objective: Exposure to environmental tobacco smoke has been reported to be a risk factor for childhood otitis media. The effect of parental smoking on the risk of otitis media after the insertion of tympanostomy tubes is unknown. We evaluated the effect of parental smoking on the risk of recurrent otitis media in children who had received tympanostomy tubes.

Methods: We enrolled 217 children aged 1-4 years who underwent insertion of tympanostomy tubes because of middle ear disease. The children were followed-up for 12 months. Otitis media episodes were recorded in patient diaries by primary care physicians. Parental smoking habits were assessed by a questionnaire at the start of the trial and after the 12 month follow-up had ended. The main outcome measure was risk of recurrent otitis media as defined by four or more otitis media episodes after tympanostomy. Altogether 198 children completed the follow-up.

Results: Maternal smoking was associated with a highly increased risk of recurrent acute otitis media (OR 4.15, 95% CI 1.45-11.9) after the insertion of tympanostomy tubes.

Conclusion: Exposure to passive smoking is associated with four-fold risk of recurrent otitis media after tympanostomy. This finding should be used to encourage parents to stop smoking even after the insertion of tympanostomy tubes to their children.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ijporl.2007.05.010DOI Listing
August 2007

Retrospective evaluation of serum Epstein Barr virus DNA levels in 406 allogeneic stem cell transplant patients.

Haematologica 2007 Jun;92(6):819-25

Helsinki University Central Hospital, Department of Medicine, Helsinki, Finland.

Background And Objectives: An HLA-mismatched donor and a T-cell-depleted graft are known risk factors for Epstein-Barr virus (EBV) reactivation after stem cell transplantation. We studied the frequency and outcome of serum EBV DNA levels in patients transplanted with an unmanipulated graft from an HLA-identical donor.

Design And Methods: Overall, 5479 serial serum samples from 406 consecutive allogeneic stem cell transplant recipients were analyzed retrospectively for EBV DNA with quantitative polymerase chain reaction (PCR).

Results: EBV DNA was found in the serum of 56 of the 406 patients (14%). EBV positivity was seen in 9 % of the recipients of a graft from a sibling donor and in 29 % of those with an unrelated donor. EBV-PCR positivity resolved without specific treatment in a third of the cases, in another third the copy number increased progressively or was high in the last serum sample, and in the remaining third the copy numbers were low in all positive sera including the last sample. In multivariate analysis antithymocyte globulin given for any reason and grade III-IV acute graft-versus-host disease were the only statistically significant risk factors for EBV reactivation. Only 8/56 patients with EBV-DNA positivity were alive at the time of the present analysis. The outcome of EBV-PCR positivity could not be predicted by the copy number or the timing of the first positive sample.

Interpretation And Conclusions: EBV reactivation was a common phenomenon in allogenic stem cell transplant recipients. In many patients the viremia resolved without EBV-directed treatment. Severe acute graft-versus-host disease and antithymocyte globulin given for any reason were risk factors for EBV viremia.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3324/haematol.10751DOI Listing
June 2007

HPV DNA testing as an adjunct in the management of patients with low grade cytological lesions in Finland.

Acta Obstet Gynecol Scand 2007 ;86(3):367-72

Department of Pathology, Helsinki University Central Hospital, Finland.

Background: Patients with recurrent low grade cytological abnormalities are at increased risk for high grade lesions. We wanted to see whether these patients could be identified by HPV DNA and pap tests.

Methods: A prospective study of 663 patients referred for a colposcopy on the basis of ASC-US or LSIL cytology. High-risk HPV DNA positivity and cytology were compared with histology.

Results: In total 65.6% samples were positive for HC2, and the overall proportion of CIN2+ lesions was 14.6%. No CIN2+lesions were found in patients testing HC2-, pap-. There were 5/97 (5.2%) high grade lesions, which were HC2-negative but pap-positive, including 1 cervical adenocarcinoma in situ. The corresponding histological sections were all positive for p16INK in immunostaining. In further analysis by PCR, 3 samples were positive for HPV DNA. High-risk HPV type 67, which is not included in the HC2 probe cocktail, was found in 1 case, and 2 cases were HPV positive but could not be typed. One CIN3 and one AIS remained HPV negative. In these 5 cases, the concomitant pap smear showed ASC-USx1, LSILx1, HSILx2 and AGCx1. During 6-month follow-up, a relatively high number of CIN2+(28/557, 5.0%) emerged from the non-CIN-CIN1 group.

Conclusions: The HC2 test or pap test alone were not sensitive enough to detect all CIN2+lesions. A relatively high number of CIN2+cases emerged from the non-CIN-CIN1 group after 6 months. Adequate follow-up of patients with mild cytological abnormalities, including a repeat pap smear taken during colposcopy and control at 6 months is underscored. Combination of hrHPV DNA and pap test should be considered, since it had high negative predictive value.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/00016340601185343DOI Listing
April 2007