This is the largest epidemiological study of AIH in a geographically defined region and demonstrates that the prevalence of AIH in the Netherlands is uncommon. Although familial occurrence of AIH is extremely rare, our twin data may point towards a genetic predisposition. The high percentage of patients with cirrhosis or fibrosis at diagnosis urges the need of more awareness for AIH.

No abstract

Human papillomavirus (HPV) infection has been etiologically linked to oropharyngeal squamous cell carcinoma (OPSCC). The prevalence of HPV-positive OPSCC varies between studies, ranging from 20 to 90%. This may be related to the lack of a standardized HPV detection assay as well as to the time period in which HPV prevalence is investigated, as rising incidence rates are reported over the last decades. Here, we validated our previously defined test algorithm for HPV detection in formalin-fixed paraffin-embedded (FFPE) tumor specimen consisting of p16 INK4A immunostaining followed by high-risk HPV DNA detection by GP51/61 PCR on the positive cases (Smeets et al., Int J Cancer 2007;121:2465-72). In addition, we analyzed HPV prevalence rates in OPSCCs in the years 1990-2010. The test algorithm was validated on a consecutive series of 86 OPSCCs collected during 2008-2011, of which both fresh frozen and FFPE samples were available. We performed HPV-E6 RT-PCR on the frozen samples as gold standard and applied the algorithm to the corresponding FFPE samples. The test algorithm showed an accuracy of 98%. Using the validated algorithm, we determined the presence of an oncogenic HPV infection in 240 OPSCCs of patients diagnosed in the years 1990-2010 at our center. A significant increase in the proportion of HPV-positive samples was observed, from 5.1% in 1990 to 29.0% in 2010 (p 5 0.001). In conclusion, we confirmed the accuracy of the test algorithm for HPV detection in FFPE tumor specimen and we found a significant increase in the prevalence of HPV in OPSCC over the last two decades at our center.Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer worldwide, accounting for $4% of all tumors. 1 Tobacco smoking and alcohol consumption are the main risk factors in the etiology of HNSCC. Over the last three decades, it has become clear that infection with high-risk human papillomavirus (HPV) is also etiologically linked to the development of HNSCCs, particularly those carcinomas that arise in the oropharyngeal region. HPV-positive oropharyngeal squamous cell carcinomas (OPSCCs) are considered to be a different tumor entity, based on prominent biological and epidemiological differences, when compared to the HPV-negative OPSCCs. 2 The biological characteristics of HPV-positive OPSCCs are distinct with respect to gene expression profiles, patterns of genetic changes, frequency of mutations in TP53 and expression of p16 INK4A (p16), encoded by the CDKN2A gene. 2,3 Epidemiologically, it has been reported that most patients with HPV-positive OPSCC are younger, are less likely to have a history of tobacco and alcohol use and have a higher number of sexual partners, in particular oral sex partners, than patients with HPV-negative OPSCC. 4-7 Furthermore, survival is markedly better for patients with an HPV-positive OPSCC, despite the fact that HPV-positive OPSCCs often present as poorly differentiated, aggressively growing tumors, that have already metastasized to the lymph nodes in the neck. [8][9][10][11]...

Histological subtyping of pulmonary adenocarcinoma has recently been updated based on predominant pattern, but data on reproducibility are required for validation. This study first assesses reproducibility in subtyping adenocarcinomas and then assesses further the distinction between invasive and non-invasive (wholly lepidic) pattern of adenocarcinoma, among an international group of pulmonary pathologists. Two ring studies were performed using a micro-photographic image-based method, evaluating selected images of lung adenocarcinoma histologic patterns. In the first study, 26 pathologists reviewed representative images of typical and ‘difficult’ histologic patterns. A total number of scores for the typical patterns combined (n = 94) and the difficult cases (n = 21) were 2444 and 546, respectively. The mean kappa score (± s.d.) for the five typical patterns combined and for difficult cases were 0.77 ± 0.07 and 0.38 ± 0.14, respectively. Although 70% of the observers identified 12–65% of typical images as single pattern, highest for solid and least for micropapillary, recognizing the predominant pattern was achieved in 92–100%, of the images except for micropapillary pattern (62%). For the second study on invasion, identified as a key problem area from the first study, 28 pathologists submitted and reviewed 64 images representing typical as well as ‘difficult’ examples. The kappa for typical and difficult cases was 0.55 ± 0.06 and 0.08 ± 0.02, respectively, with consistent subdivision by the same pathologists into invasive and non-invasive categories, due to differing interpretation of terminology defining invasion. In pulmonary adenocarcinomas with classic morphology, which comprise the majority of cases, there is good reproducibility in identifying a predominant pattern and fair reproducibility distinguishing invasive from in-situ (wholly lepidic) patterns. However, more precise definitions and better education on interpretation of existing terminology are required to improve recognition of purely in-situ disease, this being an area of increasing importance.

Tumor HPV status is a strong and independent prognostic factor for survival among patients with OPSCC. A prognostic risk model was proposed, based on our large, unselected cohort of patients with HPV status, comorbidity and nodal stage being the important prognostic factors. In addition, this study emphasizes the importance of performing an HPV DNA-specific test besides p16-immunostaining.