Detection of Human Papillomavirus Infection and p16 Immunohistochemistry Expression in Bladder Cancer with Squamous Differentiation

OBJECTIVES: To determine the potential association between HPV infection and the squamous cell component of urothelial carcinoma (UC) of the bladder and to validate p16 overexpression as a surrogate marker for HPV infection in these cancers among Koreans. METHODS: We analyzed the presence of HPV infection using an HPV-DNA chip and the expression of p16 using immunohistochemistry in 47 subjects between July 2001 and March 2011. The study group (n = 35) included patients with squamous differentiation of UC of the bladder. The control group (n = 12) included patients with squamous metaplasia of the bladder. RESULTS: Baseline characteristics of control and study groups were similar. HPV DNA detection rates were approximately 2-fold higher in the study than the control group (17.1% [6/35] versus 8.3% [1/12], respectively), but the difference was not statistically significant. P16 overexpression was detected in 16/35 (45.7%) study group and 1/12 (8.3%) control group samples (p = 0.034). Both HPV-positivity and p16 overexpression were present in 3/35 (8.8%) study group samples, but none of the control group (p = 0.295). In the study group, the percentage of HPV-positive cases who were non-smokers was 2-fold higher than the percentage of HPV-negative cases who were non-smokers (66.7% [4/6] versus 31.0% [9/29], respectively); however, statistical significance was not achieved due to the small sample size. CONCLUSIONS: HPV infection may be associated with UC of the bladder with squamous differentiation, especially in non-smokers. However, p16 expression does not appear to be a strong surrogate marker for evidence of HPV infection in this type of cancer

The Expression Patterns of p53 and p16 and an Analysis of a Possible Role of HPV in Primary Adenocarcinoma of the Urinary Bladder

BackgroundPrimary adenocarcinoma of the urinary bladder is rare. The molecular and cellular events leading to its pathogenesis are not well delineated. The goal of this study was to investigate p53 and p16 expression, as well as HPV status, in a relatively large series of primary bladder adenocarcinomas.Materials and methodsThirty six cases of urinary bladder adenocarcinoma were chosen from participating institutions. The diagnosis and available clinical history were reviewed in each case. Immunostains for p53, p16 and HPV and high-risk and low-risk HPV-ISH were performed on all tumors.ResultsPatients had an average age of 61 years with a male predominance (1.5 ∶ 1 male ∶ female ratio). The average tumor size in cystectomy specimens was 4.3 cm. Of the cases managed by transurethral resection, 40% were pT2 at the time of diagnosis. In cystectomy specimens, 77% were either pT3 or pT4. Strong nuclear p16 expression was seen in 67% of all cases and p53 expression was present in 58% of the cases. Expression of both markers was seen in 33% of cases. Expression of p16 or p53 alone was present in 12 (33%) and 9 (25%) cases, respectively. Neither marker was expressed in only 3 (8%) of the tumors. No significant correlation between clinical variables and any of the markers we studied was identified. No HPV infection was detected in any case.ConclusionsExpression of p53 and/or p16 is very common in urinary bladder adenocarcinoma. These findings implicate a high likelihood that alterations in these cell cycle proteins contribute to the pathogenesis of these tumors. Despite frequent immunohistochemical labeling for p16, no evidence of HPV infection was found

Human papillomavirus is not associated to non-small cell lung cancer: data from a prospective cross-sectional study

Background: The pathogenesis of lung cancer is triggered by a combination of genetic and environmental factors, being the tobacco smoke the most important risk factor. Nevertheless, the incidence of lung cancer in non-smokers is gradually increasing, which demands the search for different other etiological factors such as occupational exposure, previous lung disease, diet among others. In the early 80's a theory linked specific types of human papillomavirus (HPV) to lung cancer due to morphological similarities of a subset of bronchial squamous cell carcinomas with other HPV-induced cancers. Since then, several studies revealed variable rates of HPV DNA detection. The current study aimed to provide accurate information on the prevalence of HPV DNA in lung cancer. Methods: Biopsies were collected from 77 newly diagnosed non-small cell lung cancer (NSCLC) patients treated at the Thoracic Oncology Department at Barretos Cancer Hospital. The samples were formalin fixed and paraffin embedded (FFPE), histologic analysis was performed by an experienced pathologist. DNA was extracted from FFPE material using a commercial extraction kit and HPV DNA detection was evaluated by multiplex PCR and HPV16 specific real-time PCR. Results: HPV was not identified in any of the samples analysed (69). Conclusions: Our data demonstrated a lack of HPV DNA in a series of NSCL cancers.This work was funded by Conselho Nacional de Desenvolvimento Científico e Tencnológico (CNPq) [Grants number 401775/2012–7 to ALF; 573799/ 2008–3 to LLV]; Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) [Grants numbers 2014/23414–8 to EMS; 08/57889–1 to LLV]