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      Tumor risk markers in recurrent respiratory papillomatosis

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          Abstract

          Abstract Objectives: This study aims to investigate the pattern of immunoexpression of proteins p16, p53 and Ki-67 in RRP, as well as to evaluate its influence on the number of surgeries that patients have undergone to date and to analyze the benefit of immunohistochemistry in this disease. Methods: Clinical-demographic data and tumor samples were obtained from 33 patients with RRP. The expression of proteins p16, p53 and Ki-67 was analyzed by immunohistochemical method. Results: Most patients had already undergone more than one surgery. The p16 marker was negative in 24.2% of the cases, with little positivity in 27.3% of the cases, moderate in 36.4% and intense in 12.1%. The p53 marker was positive in all cases, with little immunoexpression in 39.4% of cases, moderate in 36.4% and intense in 24.2%. The Ki-67 marker showed nuclear positivity in all lesions, although in varying degrees, with a mean proliferative index ±SD (standard deviation) of 51.7±26. Conclusions: The papillomatous lesions had varying degrees of immunoexpression of proteins p16, p53 and Ki-67, but no specific immunohistochemical pattern was observed. It was found, with statistical difference, that the number of surgeries was higher in cases with greater intensity of p53 expression, without correlation with the other markers. The benefit of immunohistochemistry in recurrent respiratory papillomatosis may lie in the prognostic assessment. However, further studies are needed to evaluate the use of this technique for this purpose. Level of evidence:: 4.

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          Most cited references24

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          Human Papillomavirus and Rising Oropharyngeal Cancer Incidence in the United States

          Journal of Clinical Oncology, 29(32), 4294-4301
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            Human papillomavirus as a risk factor for the increase in incidence of tonsillar cancer.

            Smoking and alcohol are well-known etiological factors in tonsillar cancer. However, as in cervical cancer, human papillomavirus (HPV) is currently found in a sizable proportion of tonsillar cancer. Recent reports from the U.S. and Finland show an increase in the incidence of tonsillar cancer, without a parallel rise in smoking and alcohol consumption. This study investigates whether the incidence of tonsillar cancer has also changed in Sweden and whether a possible explanation of the increase is a higher proportion of HPV-positive tonsillar cancer. The incidence of tonsillar cancer between 1970 and 2002 in the Stockholm area was obtained from the Swedish Cancer Registry. In parallel, 203 pretreatment paraffin-embedded tonsillar cancer biopsies taken during 1970-2002 from patients in the Stockholm area were tested for presence of HPV DNA by PCR. The incidence of tonsillar cancer increased 2.8-fold (2.6 in men and 3.5 in women) from 1970 to 2002. During the same period, a significant increase in the proportion of HPV-positive tonsillar cancer cases was observed, as it increased 2.9-fold (p < 0.001). The distribution of HPV-positive cases was 7/30 (23.3%) in the 1970s, 12/42 (29%) in the 1980s, 48/84 (57%) in the 1990s and 32/47 (68%) during 2000-2002. We have demonstrated a highly significant and parallel increase both in the incidence of tonsillar cancer and the proportion of HPV-positive tumors. Hence, HPV may play an important role for the increased incidence of tonsillar cancer. This should definitely influence future preventive strategies as well as treatment for this type of cancer.
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              p16 positive oropharyngeal squamous cell carcinoma:an entity with a favorable prognosis regardless of tumor HPV status.

              In the human papillomavirus (HPV) era, the best way to assess oropharyngeal squamous carcinomas (SCC) for risk stratification is not clear. Many recommend use of both p16 immunohistochemistry and HPV in situ hybridization (ISH). A significant minority of tumors are p16 positive and HPV ISH negative, the significance of which is unclear. Two hundred thirty-nine oropharyngeal SCC were tested by immunohistochemistry for p16 and by ISH for high-risk HPV. For p16 positive, HPV ISH negative cases, PCR was conducted for HPV. The findings were correlated with pathologic and clinical findings. Of the 239 cases, 187 (78%) were positive for p16. Of these, 139 (74%) were positive for HPV by ISH. Of the remaining 48 cases, 45 had material for PCR. Nineteen were positive for HPV, leaving a group of 26 p16 positive and HPV undetectable SCCs. In the p16 positive cohort, there was no difference in survival between HPV ISH positive and negative cases. Comparing the HPV ISH positive and HPV ISH and PCR negative SCC, there was again no difference in survival. p16 positive, HPV negative SCC still had significantly better survival than p16 negative SCC in univariate and multivariate analysis. Outcomes for p16 positive, HPV negative oropharyngeal SCC are not significantly different from p16 positive, HPV positive tumors and are significantly better than for p16 negative tumors. These results suggest that p16 immunohistochemistry alone is the best test to use for risk stratification in oropharyngeal SCC.
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                Author and article information

                Journal
                bjorl
                Brazilian Journal of Otorhinolaryngology
                Braz. j. otorhinolaryngol.
                Associação Brasileira de Otorrinolaringologia e Cirurgia Cérvico-Facial. (São Paulo, SP, Brazil )
                1808-8694
                1808-8686
                April 2023
                : 89
                : 2
                : 285-291
                Affiliations
                [2] Curitiba PR orgnameHospital IPO orgdiv1Instituto Paranaense de Otorrinolaringologia orgdiv2Departamento de Otorrinolaringologia Brazil
                [3] Curitiba PR orgnameHospital IPO orgdiv1Instituto Paranaense de Otorrinolaringologia orgdiv2NEP Brazil
                [1] Curitiba Paraná orgnameUniversidade Federal do Paraná Brazil
                Article
                S1808-86942023000200285 S1808-8694(23)08900200285
                10.1016/j.bjorl.2022.10.049
                0cb88317-1f16-44a8-aa97-c7386a379d83

                This work is licensed under a Creative Commons Attribution 4.0 International License.

                History
                : 16 August 2022
                : 03 October 2022
                Page count
                Figures: 0, Tables: 0, Equations: 0, References: 24, Pages: 7
                Product

                SciELO Brazil

                Categories
                Original Articles

                Recurrent respiratory papillomatosis,Immunohistochemistry,Protein p16,Protein 53,Protein Ki-67

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