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High risk human papillomavirus (hrHPV) based screening provides the possibility of vaginal self‐sampling as a tool to increase screening attendance. In order to evaluate the impact and feasibility of opt‐in self‐sampling in the Finnish setting, we invited a randomized population of 5350 women not attending screening after age group invitation or after reminder, to attend HPV self‐sampling‐based screening in the autumn of 2018 in Helsinki. Out of those, 1282 (24.0%) expressed their interest and ordered the sampling package. Eventually 787 women (14.7% of the total invited population) took part in screening, 770 women by providing a vaginal sample within 2 months from invitation and 17 by providing a pap smear in the laboratory. Self‐taken samples were collected in Aptima Multitest vials and tested using the Aptima HPV mRNA assay. A high proportion, 158/770 (20.5%) of the samples were positive in the Aptima HPV assay. One hundred and forty‐one samples were further submitted to Aptima HPV Genotyping and extended genotyping by a Luminex based assay. Of those, 23 samples (16.3%) were HPV 16 positive and 7 (5.0%) were positive for HPV 18/45; extended genotyping revealed multiple high‐risk and low‐risk HPV genotypes. At follow‐up seven cases of high‐grade squamous intraepithelial lesion (HSIL) were diagnosed, which represents 4.4% of HPV positive women and 0.9% of screened women, whereas the rate was 0.5% in routine screening. Our findings suggest that self‐sampling with HPV mRNA testing is a feasible approach to improve screening efficacy in a high‐risk population among original nonattendees. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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 [ABSTRACT FROM AUTHOR]

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 2.5/105 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. [ABSTRACT FROM AUTHOR]

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. © 2008 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]

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-US×1, LSIL×1, HSIL×2 and AGC×1. 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. [ABSTRACT FROM AUTHOR]

The number of T cells that have undergone proliferation after antigen stimulation in vivo must be controlled to prevent excessive accumulation of T cells, autoimmunity, and T cell neoplasia. We describe here that primary human adenotonsillar memory phenotype CD45R0 CD4 T cells, but not adenotonsillar naive-phenotype CD45RA CD4 T cells, or peripheral blood naive or memory CD4 T cells, express high levels of activation-associated antigens CD38, CD69, CD71, and HLA-DR. These in vivo-activated CD45R0 CD4 T cells were susceptible to spontaneous and rapid apoptosis in vitro. Apoptosis could not be inhibited by the disruption of Fas-Fas ligand engagement or by the pan-caspase inhibitor ZVAD. Cross-linking of the T cell antigen receptor did not rescue cells from apoptosis. Apoptosis could be partially inhibited by the chemokine CXCL12/SDF-1, by IL-6, and by the IL-2 receptor common γ chain-signaling cytokines IL-2, -7, and -15. Inhibitors of phosphatidylinositol 3-kinase accelerated apoptosis. We conclude that after in vivo activation of CD45R0 CD4 T cells, the cells experience a period of intrinsically elevated sensitivity to apoptosis and that multiple external signals control their survival. [ABSTRACT FROM AUTHOR]

Mattila PS, Hammarén-Malmi S, Tarkkanen J, Saxen H, Pitkäniemi J, Karvonen M, Tuomilehto J. Adenoidectomy during early life and the risk of asthma. Pediatr Allergy Immunol 2003: 14: 358–362. © 2003 Blackwell Munksgaard The objective of the study was to evaluate the risk of asthma in children who had undergone an adenoidectomy, an operation frequently performed on children with glue ear or recurrent otitis media. Two surveys were carried out, a nation-wide questionnaire returned by 483 individuals (survey A) and a survey of hospital discharge records involving 1616 children who had undergone an adenoidectomy and 161 control children who had undergone probing of the nasolacrimal duct due to congenital obstruction (survey B). The questionnaire (survey A) showed that an adenoidectomy before the age of 4 years was associated with asthma (OR 3.19, 95% CI 1.25; 8.13) and with allergy to animal dust (OR 2.50, 95% CI 1.27; 4.95). In survey B, asthma diagnosis was retrieved from the national asthma register. It showed also that adenoidectomy at an early age was associated with an increased risk of asthma (OR 6.74, 95% CI 2.99; 15.2). There was an association between asthma and adenoidectomy, even before adenoidectomy had actually been performed. The risk of asthma was highest among children who had had adenoidectomy because of recurrent otitis media. The observed association between an adenoidectomy and asthma may be explained by an underlying factor predisposing to both recurrent otitis media and asthma. [ABSTRACT FROM AUTHOR]

Background: We conducted a quality improvement project in a cervical cancer screening programme in Helsinki in order to see if detection of precancerous lesions could be influenced by external (participation rate) and internal (laboratory praxis) quality measures.Methods: In order to increase the participation rate, a second personal invitation to Pap-test was mailed to nonparticipants of the first call. In order to improve the quality of screening, the cytotechnicians monitored their performance longitudinally by recording the number of slides reviewed per day, the pick-up rate of abnormal smears, the report of the consulting cytopathologist, and the number of histologically verified lesions detected from the cases that they had screened. Regular sessions were held to compare the histological findings with the cytological findings of all cases referred for colposcopy. No pressure was applied on the cytotechnicians to ensure that they felt comfortable with their daily workload.Results: A total of 110 000 smears were screened for cervical cancer at the Helsinki City Hospital during 1996-99. Initially, the overall participation rate increased from 62% to 71%. The number of histologically confirmed precancerous lesions (CIN 1-3) more than doubled and their detection rate increased from 0.32% to 0.72%.Conclusions: Continuous education and feedback from daily work performance were important, yet rather inexpensive means in increasing laboratory performance. Additional measures are needed to further increase the participation rate. Impact of the quality measures on cancer incidence needs to be assessed later on. [ABSTRACT FROM AUTHOR]

The presence of Epstein–Barr virus (EBV), human papilloma virus (HPV), and cytomegalovirus (CMV) was studied in 20 patients who developed malignancies after heart transplantation in the Helsinki University Central Hospital. The tumors were analyzed for the presence of HPV by polymerase chain reaction and for EBV by in situ hybridization. Clinical CMV infection was verified by immunochemical quantitation of CMV antigen in peripheral blood cells. HPV was detected in one of the eight epithelial malignant tumors studied. Three of the six lymphomas were positive for EBV. Two (67%) of 3 patients with EBV-positive lymphomas and one (33%) of the other three lymphomas but only 2 (14%) of 14 patients who developed other malignancies had a history of a manifest post-transplantation CMV infection prior to the development of malignancy. These results confirm the presence of EBV in lymphomas of heart transplant recipients and suggest that CMV might have a contributory role in the development of EBV-associated lymphomas. [ABSTRACT FROM AUTHOR]