Increasing incidence of base of tongue cancers from 2000 to 2010 due to HPV: the largest demographic study of 210 Danish patients.

BACKGROUND: We assessed the development in the number of new base of tongue squamous-cell carcinoma (BSCC) cases per year in eastern Denmark from 2000 to 2010 and whether HPV may explain any observable increased incidence. METHODS: We performed HPV DNA PCR and p16 immunohistochemistry analysis for all (n=210) BSCCs registered in the Danish Head and Neck Cancer Group (DAHANCA) and the Danish Pathology Data Bank, and genotyped all HPV-positive specimens with amplicon-based next-generation sequencing. RESULTS: The overall crude incidence of BSCCs increased significantly (5.4% per year) during the study period. This was explained by a significant increase in the number of HPV-positive BSCCs (8.1% per year), whereas the number of HPV-negative BSCCs did not increase significantly. The overall HPV prevalence was 51%, with HPV16 as the predominant HPV type. CONCLUSIONS: The increased number of HPV-positive BSCCs may explain the increasing incidence of BSCCs in eastern Denmark, 2000-2010.

Human papilloma virus and p53 expression in carcinomas associated with sinonasal papillomas: a Danish Epidemiological study 1980-1998.

OBJECTIVES: To determine a putative role and relation between human papilloma virus (HPV) and p53 in the etiology of sinonasal carcinomas associated with papillomas. STUDY DESIGN: The study group consists of all patients with sinonasal carcinomas associated with papillomas diagnosed in Denmark from 1980 to 1998. After reviewing our national pathological files, tumor tissues from 36 patients were collected, comprising 15% of the total cases of sinonasal carcinomas. In 35 cases a squamous cell carcinoma was demonstrated and in one case an adenocarcinoma was evident. Inverted papilloma was associated with carcinoma in 31 cases and exophytic papillomas in 5 cases. The material was investigated for HPV using polymerase chain reaction analyses with two sets of consensus primers (GP5+/GP6+ and MY09/MY11). The HPV-positive cases were submitted to dot-blot hybridization to establish the HPV type. Using immunohistochemistry, the p53 expression was determined. A p53 overexpression is defined as positive staining in 10% or more of the tumor cells. RESULTS: Among 30 examined cases of carcinomas associated with inverted papillomas, 4 cases were HPV-positive (13%). P53 overexpression was not shown among the HPV-positive cases, whereas p53 overexpression was seen in 21 of the 24 (88%) examined HPV-negative cases. Among the 5 carcinomas associated with exophytic papillomas, HPV was demonstrated together with p53 overexpression in 3 cases (60%). In addition, one case more was with p53 overexpression. CONCLUSION: An inverse relation between HPV and p53 overexpression in sinonasal carcinomas associated with inverted papillomas appears to have been demonstrated. HPV and p53 might also have an etiological role among the carcinomas associated with exophytic papillomas.

Expression of p53 in normal nasal mucosa and in sinonasal papillomas with and without associated carcinoma and the relation to human papillomavirus (HPV).

The aim of the present study was to investigate the expression of p53 in sinonasal papillomas, carcinomas ex papillomas and normal nasal mucosa. Furthermore, we wanted to study the expression of p53 in relation to the presence of human papilloma virus (HPV). Immunohistochemical staining was performed on 37 formalin-fixed paraffin-embedded biopsies comprising seven biopsies from normal nasal mucosa, 13 papillomas of an exophytic growth pattern, 12 papillomas of an endophytic growth pattern and five carcinomas. The level of p53 overexpression was defined as more than 5% positive nuclei. The normal nasal mucosa showed no positive nuclei. The papillomas of both exophytic and endophytic growth patterns showed scattered positive nuclei, but in all cases this was less than 5%. p53 was overexpressed in three out of five carcinomas. In conclusion, we found an overexpression of p53 in carcinomas occurring in sinonasal papillomas but not in the benign tumours of the sinonasal mucosa. Thus, this report supports the concept that p53 may have a role in the carcinogenic process in head and neck tumours.

Carcinomas occurring in papillomas of the nasal septum associated with human papilloma virus (HPV).

Carcinomas arising in pre-existing sinonasal papillomas of the nasal septum are rare. To our knowledge only one case has been reported. We report two cases of carcinomas occurring in septal papillomas. In the first case a carcinoma developed in an exophytic papilloma 16 years after the first operation for a papilloma. In the second case a carcinoma was present at the first presentation within an inverted papilloma, and a metastasis had also developed. In the first case HPV type 6/11 was demonstrated by in-situ hybridisation and PCR in the original papilloma as well as in the recurrent papilloma and in the carcinoma. In the second case HPV type 18 was found in the nasal lesion as well as in the metastasis. All samples were examined for Epstein-Barr virus (EBV) by PCR, but with negative results. We believe that case one is the first reported case of carcinomatous transformation within an exophytic septal papilloma.

Comparison of the reproducibility of the WHO classifications of 1975 and 1994 of endometrial hyperplasia.

In a blinded, randomized design, six histopathologists with an interest in gynecological pathology examined the inter- and intraobserver variation of the histopathological diagnosis of endometrial hyperplasia according to the World Health Organization (WHO) classification of 1975 and the new WHO classification of 1994. On four occasions, the pathologists assessed hematoxylin/eosin-stained slides from 128 cases originally diagnosed and coded in the Snomed system as endometrial hyperplasia. In the first and third rounds, the slides were classified according to the 1975 classification and in the second and fourth rounds according to the 1994 classification. The overall interobserver agreement in the two rounds where the 1975 classification was used was 0.47 and 0.51, and the kappa values 0.24 [95% confidence interval (CI) 0.21-0.27] and 0.30 (95% CI 0.27-0.33). The overall interobserver agreement in the two rounds using the 1994 classification was 0.45 and 0.41 and the kappa values 0.25 (95% CI 0.23-0.28) and 0.20 (95% CI 0.17-0.22). Reducing the classification to two categories with clinical significance (atypical endometrial hyperplasia versus others in the 1975 classification, and atypical endometrial hyperplasia, complex versus others in the 1994 classification) increased the overall agreement of the 1975 classification in both rounds to 0.91 and of the 1994 classification to 0.92 and 0.90. The kappa values increased to 0.54 (95% CI 0.49-0.58) and 0.49 (95% CI 0.45-0.54) in the 1975 classification and to 0.59 (95% CI 0.54-0.63) and 0.42 (95% CI 0.37-0.46) in the 1994 classification. The intraobserver overall agreement for the 1975 classification ranged from 0.80 to 0.55 and the kappa values from 0.70 (95% CI 0.58-0.81) to 0.28 (95% CI 0.17-0.39). The intraobserver overall agreement for the 1994 classification ranged from 0.71 to 0.46 and the kappa values from 0.60 (95% CI 0.51-0.70) to 0.20 (95% CI 0.09-0.30). It is concluded that there is considerable inter- and intraobserver variation using both the 1975 and the 1994 classifications of endometrial hyperplasia. We propose that there is need for a specification and for a simplification of the classification.

Carcinoid tumour of the breast.

A case of primary carcinoid in the female breast is reported. The patient was treated by segmental mastectomy and is without local recurrence and signs of carcinoid tumour at any other site after 3 years of observation.

Sinonasal papillomas: a report of 82 cases in Copenhagen County, including a longitudinal epidemiological and clinical study.

The present epidemiological and clinical study comprises 82 patients with sinonasal papillomas diagnosed from 1975 to 1993. Histology showed 58 cases of inverted papillomas including 5 cases of associated carcinoma, 19 cases of exophytic papilloma, and 5 cases of columnar cell papilloma. The incidence of sinonasal papillomas in Copenhagen County was 0.74 per 100,000 inhabitants per year. The inverted and columnar cell papillomas were typically located in the middle meatus with a varying degree of involvement of the adjacent sinuses. The exophytic papillomas were predominantly located multicentrically on the nasal septum. Good results of treatment, especially with regard to inverted papillomas, were not correlated to the aggressiveness of surgery. A lateral rhinotomy with medial maxillectomy was performed as primary surgery in 28 patients. In 50% of these patients there were recurrences. The preliminary results of endonasal endoscopic surgery revealed a high success rate, i.e., no recurrences in 5 cases so far. The septal papillomas were typically resected by a simple endonasal procedure. There were recurrences in 66% of these cases. The midfacial degloving procedure may be advocated instead of or as a supplement to the lateral rhinotomy if the tumor cannot be visualized sufficiently by endoscopy. Smoking may dispose to sinonasal papillomas.

Human papillomavirus (HPV) in sinonasal papillomas: a study of 78 cases using in situ hybridization and polymerase chain reaction.

To determine the role of human papillomavirus (HPV) in the etiology of sinonasal papillomas, 57 inverted papillomas including 5 cases associated with carcinomas, 16 exophytic papillomas, and 5 cases of columnar cell papillomas were examined for the presence of HPV DNA by in situ hybridization and polymerase chain reaction (PCR). The genetic studies were performed on the formalin-fixed, paraffin-embedded material. In only 6% of the 52 benign inverted papillomas was HPV DNA identified, whereas 69% of the exophytic papillomas were infected by HPV DNA. In none of the 5 cases with columnar cell papillomas could HPV be demonstrated. HPV 6/11 was identified in all of these HPV-positive cases. In the carcinoma area, HPV was detected in 2 (1 HPV 6/11 and 1 HPV 18) of the 5 inverted papillomas associated with carcinomas. The findings confirm the presence of HPV DNA in sinonasal papillomas. The results also indicate that HPV 6/11 may be involved in the pathogenesis of, solely, exophytic papillomas. We found that in situ hybridization and PCR seem equally sensitive in detecting HPV in sinonasal papillomas.

Human papillomavirus and normal nasal mucosa: detection of human papillomavirus DNA in normal nasal mucosa biopsies by polymerase chain reaction and in situ hybridization.

To determine a possible etiological role of human papillomavirus (HPV) in sinonasal papillomas and squamous cell carcinomas, it is necessary to investigate normal nasal mucosa of healthy persons for the presence of HPV. The material in the present study consists of 21 biopsies taken from the inferior concha of 21 otherwise healthy persons who underwent surgery for nose fractures or nasoseptal deviations. In addition, five inferior conchae were obtained from persons who had died of non-neoplastic diseases. HPV was not detected in any of these specimens, either by polymerase chain reaction or by in situ hybridization. Histologic evaluation showed that squamous metaplasia was a common finding in the biopsies. The presence of HPV in sinonasal papillomas and carcinomas may indicate that HPV is an etiological factor in these lesions.

[Occurrence of lung cancer in Denmark 1943-1986. Reliability of the cancer registry]. / Forekomsten af lungekraeft i Danmark 1943-1986. Cancerregisterets pålidelighed.

A rise in the number of adenocarcinomas of the lung and a fall in squamous cell carcinomas are seen in Denmark since 1978; a change based on a growing number of lung cancers among women with an excess of adenocarcinomas. A fall in the frequency of autopsies in Denmark will entail the loss of an essential control of the quality of diagnosis of lung cancer, primary or secondary, and make future descriptive studies difficult to interpret. The validity of morphologic diagnosis of lung cancer as recorded by the Danish Cancer Registry during 1943-1986 was assessed. We extracted a stratified random sample of 5% of all recorded cases prior to 1978, these were then recorded according to the ICD-O classification. Cases after 1978 were originally coded in the Registry according to ICD-O, here we checked the coding against the original reports. The information on morphology prior to 1978 was too inprecise to merit evaluation of trends and proportionate distributions by morphology. After 1978 data was adequate, and after 1983 very precise.

Tracheobronchial involvement of laryngeal papillomatosis at onset.

A case of adult onset laryngeal papillomas with tracheal and bronchial involvement present at onset is presented. The presence of human papilloma virus (HPV) DNA type 6/11 is demonstrated by in situ hybridization.

The presence of human papillomavirus in sinonasal papillomas, demonstrated by polymerase chain reaction with consensus primers.

The frequency of human papillomavirus (HPV) in sinonasal papillomas seems to vary considerably. The highest frequencies have been reported by investigators using in situ DNA or RNA hybridization. Few studies have used polymerase chain reaction, and in these reports the frequency of HPV detection is rather low. We have investigated the presence of HPV in sinonasal papillomas using the polymerase chain reaction with a set of degenerated consensus primers, which amplify the vast majority of the known HPV types. Human papillomavirus was found in three of 14 papillomas. By in situ hybridization the same three papillomas were positive for HPV type 6/11.

Adenomatoid tumor of the uterus.

A case of adenomatoid tumor of the uterus of a 49-year-old woman is described. The tumor was unusually large and atypically located in the fundus of the uterus. Adenomatoid tumors in genitals are benign but may macroscopically resemble a malignant tumor. As recurrence does not occur simple excision is sufficient.

Aspergillus fumigatus fungaemia and myocarditis in a patient with acquired immunodeficiency syndrome.

Necrotizing myocarditis due to Aspergillus fumigatus was a contributory cause of death in a patient with acquired immunodeficiency syndrome and non-Hodgkin lymphoblastic malignant lymphoma of the Burkitt type. A transient remission of the lymphoma had been obtained by cytostatic treatment. A. fumigatus was isolated from blood two weeks before death, but myocarditis was not diagnosed until autopsy.

Longitudinal study of influence of Helicobacter pylori on current risk of duodenal ulcer relapse. The Hvidovre Ulcer Project Group.

Seventy-four patients with duodenal ulcer were followed up longitudinally for 2 years after initial ulcer healing. Endoscopy including biopsy of the antral mucosa was performed every 3rd month and whenever clinical symptoms of relapse occurred. The presence of Helicobacter pylori in the biopsy specimens was scored as 0 (none), 1 (sporadic occurrence), 2 (clusters), and 3 (numerous bacteria found diffusely in the mucus layer). The incidence rates of ulcer relapse per patient-month, grouped in accordance with these scores, were (with 95% confidence intervals) 0.073 (0.048-0.111), 0.083 (0.052-0.133), 0.123 (0.096-0.157), and 0.069 (0.041-0.116), respectively. No significant differences in incidence rates across H. pylori scores were observed when taking into account the observation period after healing of the first ulcer, number of ulcer recurrence (1st, 2nd, 3rd), sex, age, smoking habits, peak acid output, time of healing of the preceding ulcer, treatment of the present ulcer (cimetidine, antacids, or no treatment), or type and degree of gastritis. Thus, although H. pylori is prevalent in patients with duodenal ulcer disease, the present study indicates that H. pylori does not have a substantial note in the precipitation of active duodenal ulcer.

Hepatic effects of dietary weight loss in morbidly obese subjects.

This prospective study was carried out in order to evaluate the influence on liver morphology and function of a very-low-calorie formula diet. Fourty-one morbidly obese, non-alcoholic subjects had liver biopsy performed before and after a median weight loss of 34 kg. Fatty change improved (p less than 0.001), but 24% of the patients developed slight portal inflammation (p = 0.039) or slight portal fibrosis (p = 0.063). Patients developing portal fibrosis had a higher degree of fatty change at entry (p = 0.029), a more pronounced reduction of fatty change (p = 0.014) and a faster weight loss (p = 0.026). Liver biochemistry, which was of no individual diagnostic value, improved. It is concluded that morbidly obese subjects with a high degree of hepatic fatty change are at risk of developing portal inflammation and fibrosis when undergoing very fast dietary weight reductions.

AIDS-related lymphoma. Histopathology, immunophenotype, and association with Epstein-Barr virus as demonstrated by in situ nucleic acid hybridization.

To investigate the range of pathology shown by acquired immune deficiency syndrome (AIDS)-related lymphomas arising in an epidemiologically well-defined group of patients, all cases of lymphoma recognized in Danish human immunodeficiency virus (HIV)-infected individuals up to the end of 1988 were studied. Twenty-seven cases (26 high-grade non-Hodgkin's lymphoma [NHL], 1 Hodgkin's disease) were found, to give a cumulative incidence rate of 8% among Danish AIDS patients. Morphologically most NHL patients were classified into two groups: 1) high-grade tumors with a predominant population of immunoblasts, either monomorphic or more often polymorphic with plasmacytic differentiation; 2) Burkitt-type. Of 26 NHLs, 22 had a B-cell paraffin-section immunophenotype and 4 were non-B, non-T. Epstein-Barr virus (EBV) DNA was demonstrated in tumor cells of 12 of 24 cases (50%) using in situ nucleic acid hybridization with a 35S-labeled probe in paraffin sections. Epstein-Barr virus DNA was found in 65% of group 1 and 20% of group 2 tumors. This study suggests the existence of two main groups of AIDS-related lymphoma with different pathogeneses. First there are immunoblast-rich lesions, which usually are associated with EBV and morphologically resemble lymphomas described in immunosuppressed organ-transplantation patients. Second there are Burkitt-type tumors in which EBV sequences are less common and that may be pathogenetically analogous to sporadic Burkitt's lymphoma.

Flutamide-induced liver failure.

Two cases of clinically manifest liver failure in patients with metastatic prostatic cancer treated with the non-steroidal antiandrogen flutamide combined with a luteinizing hormone-releasing hormone analogue are described. One patient developed severe hepatic insufficiency with jaundice, ascites and hepatic coma. The condition reversed after discontinuation of flutamide. The other patient only became jaundiced with a biochemical cholestatic pattern. Previous reports of hepatic adverse reactions only include elevated transaminase levels without clinical manifestations. The morphological lesions in the liver biopsy and the clinical condition may be due to a reversible interaction with metabolic processes in the hepatocytes.

Alcoholic hepatitis in females.

In the period 1970-1984 alcoholic hepatitis was diagnosed by liver biopsy in 52 females. Thirty-six patients with cirrhosis were generally in a worse clinical and biochemical state than those without cirrhosis. Biochemical tests for liver function showed significant improvement from admission to the time of liver biopsy. At follow-up liver function tests were generally better in patients who had stopped drinking alcohol compared to those who continued to do so. The 5-year survival rate was 82% for females without cirrhosis, and 45% for those with cirrhosis (p less than 0.03). Considering the sex-related differences in alcohol abuse in the general population we found no evidence of increased susceptibility to the hepatotoxic effect of alcohol in females.