Larinks Skuamöz Hücreli Karsinomlarının Nüks ve Sağkalımında p16 Ekspresyonunun Rolü
Year 2024,
Volume: 9 Issue: 2, 175 - 183, 02.06.2024
Nuket Özkavruk Eliyatkın
,
Asuman Feda Bayrak
,
Hacer Sena Kılıç
,
Akif İşlek
Abstract
Amaç: Larinks karsinomlarında en sık görülen histolojik tip skuamöz hücreli karsinomdur. Son yıllarda temel nedensel faktörler arasında insan papilloma virüsü (Human Papilloma Virüs, HPV)’nün de etkili olabileceği bildirilmektedir. HPV enfeksiyonunu tanımlamada immunohistokimyasal olarak p16 proteini değerlendirilmektedir. Bu çalışmanın amacı, laringeal skuamöz hücreli karsinom hastalarında uzun süreli genel sağkalım, hastalıksız sağkalım ve hastalığa özgü hastalıksız sağkalım üzerindeki p16 ekspresyonunun prognostik rolünü değerlendirmektir.
Gereç ve Yöntem: Bu çalışmada 2013-2015 yılları arasında larinks skuamöz hücreli karsinom tanısı alan hastalar elektronik ortam verilerinden kayıt edildi ve arşiv preparatları yeniden değerlendirildi. Yeterli tümör dokusu içeren ve parafin bloklarına ulaşılan hastalar çalışmaya dahil edildi. Demografik veriler, histopatolojik bulgular, tümör nüksü, sağkalım takipleri değerlendirildi. Tanıtıcı tümör alanlarını içeren doku örneklerinde p16 immunohistokimyasal boyaması yapıldı. p16 boyama yoğunluğu negatif (0), zayıf (1), orta (2) veya güçlü (3) olarak değerlendirildi. Tüm klinikopatolojik parametreler ile p16 arasındaki ilişki değerlendirildi.
Bulgular: Evre T4 kanseri olan hastaların oranı T3 evresine göre anlamlı olarak daha sık p16 negatif olarak saptandı. Hastalıksız sağkalım ve toplam sağkalım p16 durumundan (4 grup) etkilenmedi. Ancak p16 durumu pozitif ve negatif olarak ele alındığında, p16 durumunun hastalıksız sağkalıma etkisi için saptanan p değeri anlamlılık sınırında saptandı.
Sonuç: p16 ekspresyonu ile ilgili olarak literatürde çok farklı sonuçlar vardır. Biz tam sağkalım ile p16 ekspresyonu arasında bir ilişki bulduk. Yeni büyük seriler ile yapılacak çalışmalara ihtiyaç vardır.
Supporting Institution
Yok
Project Number
İzmir Katip Çelebi Üniversitesi Girişimsel Olmayan Klinik Araştırmalar Etik Kurulu (22.10.2022 tarihli 0581 karar no ile) tarafından onaylanmıştır.
References
- Karatzanis AD, Psychogios G, Waldfahrer F, Kapsreiter M, Zenk J, Velegrakis GA, et al. Management of locally advanced laryngeal cancer. J Otolaryngol Head Neck Surg. 2014;43(1):4.
- Megwalu UC, Sikora AG. Survival outcomes in advanced laryngeal cancer. JAMA Otolaryngol Head Neck Surg. 2014;140(9):855–60.
- Talamini R, Bosetti C, La Vecchia C, Dal Maso L, Levi F, Bidoli E, et al. Combined effect of tobacco and alcohol on laryn-geal cancer risk: a case-control study. Cancer Causes Control. 2002;13:957-64.
- Moore CE, Wiatrak BJ, McClatchey KD, Koopmann CF, Thomas GR, Bradford CR, et al. High-risk human papillomavirus typesand squamous cell carcinoma in patients with respiratory papil-lomas. Otolaryngol Head Neck Surg. 1999;120:698-705.
- de Oliveira DE, Bacchi MM, Macarenco RS, Tagliarini JV, CordeiroRC, Bacchi CE. Human papillomavirus and Epstein-Barr virusinfection, p53 expression and cellular proliferation in laryngealcarcinoma. Am J Clin Pathol. 2006;126:284-93.
- Münger K, Baldwin A, Edwards EM, Hayakawa H. Mecha-nisms of human papillomavirus induced oncogenesis. J Virol. 2004;78:11451- 60.
- Halec G, Holzinger D, Schmitt M, Flechtenmacher C, Dyckhoff G, Lloveras B, et al. Biological evidence for a causal role of HPV16in a small fraction of laryngeal squamous cell carcinoma. Br J Cancer. 2013;109:172-83.
- Isayeva T, Li Y, Maswahu D, Brandwein-Gensler M. Humanpapillomavirus in non-oropharyngeal head and neck can-cers: a systematic literature review. Head Neck Pathol. 2012;6: 104- 20.
- Worden FP, Kumar B, Lee JS, Wolf GT, Cordell KG, Taylor JMG, et al. Chemoselection as a strategy for organ preservation in advanced oropharynx cancer: response and survival positively associated with HPV16 copy number. J Clin Oncol. 2008;26(19):3138-46.
- Ahmadi N, Ahmadi N, Chan MV, Huo YR, Sritharan N, Chin R. Laryngeal squamous cell carcinoma survival in the context of human papillomavirus: a systematic review and meta-analysis. Cureus. 2018;10(2):e2234.
- Dahm V, Haitel A, Kaider A, Stanisz I, Beer A, Lill C. Cancer stage and pack-years, but not p16 or HPV, are relevant for survival in hypopharyngeal and laryngeal squamous cell carcinomas. Eur Arch Oto-Rhino-Laryngol. 2018;275(7):1837-43.
- Siegel RL, Miller KD, Jemal A. Cancer statistics, 2019. CA Cancer J Clin. 2019;69(1):7-34.
- Xu Y, Liu S, Yi H, Wang J, Dong P, Li X, et al. Human papillomavirus infection in 674 chinese patients with laryngeal squamous cell carcinoma. Plos One. 2014;9:e115914.
- Salazar CR, Anayannis N, Smith RV, Wang Y, Haigentz M Jr, Garg M, et al. Combined p16 and human papillomavirus testing pre-dicts head and neck cancer survival. Int J Cancer. Head Neck Pathol. 2014;8:77-87.
- Shestakova A, Tarabay J, Burtsev A, Ibe I, Kim J, Chandan V, et al. Increased PD-L1 and p16 expression are common in oropharyngeal squamous cell carcinoma. Future Sci OA. 2021;7(9):FSO768.
- Li X, Gao L, Li H, Gao J, Yang Y, Zhou F, et all. Human papillomavirus infection and laryngeal cancer risk: a systematic review and meta-analysis. J Infect Dis. 2013;207(3):479-88.
- Dogantemur S, Ozdemir S, Uguz A, Surmelioglu O, Dagkiran M, Tarkan O, et all. Assessment of HPV 16, HPV 18, p16 expression in advanced stage laryngeal cancer patients and prognostic significance. Braz J Otorhinolaryngol. 2020;86(3):351-7.
- Allegra E, Bianco MR, Mignogna C, Caltabiano R, Grasso M, Puzzo L. Role of P16 Expression in the Prognosis of Patients With Laryngeal Cancer: A Single Retrospective Analysis. Cancer Control. 2021;28:10732748211033544.
- Hernandez BY, Goodman MT, Lynch CF, Cozen W, Unger ER, Steinau M, et all; HPV Typing of Cancer Workgroup. Human papillomavirus prevalence in invasive laryngeal cancer in the United States. PLoS One. 2014;9(12):e115931.
- Meshman J, Wang PC, Chin R, John MS, Abemayor E, Bhuta S, et all. Prognostic significance of p16 in squamous cell carcinoma of the larynx and hypopharynx. Am J Otolaryngol. 2017;38(1):31-7.
- Bussu F, Sali M, Gallus R, Vellone VG, Zannoni GF, Autorino R, et all. HPV infection in squamous cell carcinomas arising from different mucosal sites of the head and neck region. Is p16 immunohistochemistry a reliable surrogate marker? Br J Cancer. 2013;108(5):1157-62.
- Vazquez-Guillen JM, Palacios-Saucedo GC, Alanis-Valdez AY, Huerta-Escobedo A, Zavala-Pompa A, Rivera-Morales LG, et al. p16INK4a and pRb expression in laryngeal squamous cell carcinoma with and without infection by EBV or different genotypes of HPV: a retrospective study. Infect Agent Cancer. 2023;18(1):43.
- Sánchez Barrueco A, González Galán F, Villacampa Aubá JM, Díaz Tapia G, Fernández Hernández S, Martín-Arriscado Arroba C, et all. p16 Influence on laryngeal squamous cell carcinoma relapse and survival. Otolaryngol Head Neck Surg. 2019;160(6):1042-7.
- Young RJ, Urban D, Angel C, Corry J, Lyons B, Vallance N, et all. Frequency and prognostic significance of p16(INK4A) protein overexpression and transcriptionally active human papillomavirus infection in laryngeal squamous cell carcinoma. Br J Cancer. 2015;17;112(6):1098-104.
- Dahm V, Haitel A, Kaider A, Stanisz I, Beer A, Lill C. Cancer stage and pack-years, but not p16 or HPV, are relevant for survival in hypopharyngeal and laryngeal squamous cell carcinomas. Eur Arch Oto-Rhino-Laryngol. 2018;275(7):1837-43.
The Role of p16 Expression in Recurrence and Survival of Laryngeal Squamous Cell Carcinomas
Year 2024,
Volume: 9 Issue: 2, 175 - 183, 02.06.2024
Nuket Özkavruk Eliyatkın
,
Asuman Feda Bayrak
,
Hacer Sena Kılıç
,
Akif İşlek
Abstract
Objective: The most common histological type in laryngeal carcinomas is squamous cell carcinoma. In recent years, it has been reported that human papilloma virus may also be effective among the main causative factors. Immunohistochemically, p16 protein is evaluated in identifying HPV infection. The aim of this study was to evaluate the prognostic role of p16 expression on long-term overall survival, disease-free survival, and disease-specific ‘progression-free’ survival in patients with laryngeal squamous cell carcinomas.
Material and Method: In this study, patients diagnosed with laryngeal squamous cell carcinoma between 2013 and 2015 were recorded from electronic media data and archive preparations were re-evaluated. Patients with consisting of sufficient tumor tissue and reached paraffin blocks were included in the study. Demographic data, histopathological findings, recurrence and survival follow-up were evaluated. p16 immunohistochemical staining was performed on tissue samples containing introductory tumor areas. The p16 staining intensity was evaluated as negative (0), weak (1), moderate (2), or strong (3). The relationship between p16 and all clinicopathological parameters was evaluated.
Results: The proportion of patients with stage T4 cancer was found to be p16 negative significantly more frequently than stage T3. Disease-free survival and overall survival were not affected by p16 status (4 groups). However, when p16 status was considered as positive and negative, the p value determined for the effect of p16 status on disease-free survival was found at the limit of significance. Conclusion: There are very different results in the literature on p16 expression. We found an association between complete survival and p16 expression. Upcoming studies with new large series are needed.
Project Number
İzmir Katip Çelebi Üniversitesi Girişimsel Olmayan Klinik Araştırmalar Etik Kurulu (22.10.2022 tarihli 0581 karar no ile) tarafından onaylanmıştır.
References
- Karatzanis AD, Psychogios G, Waldfahrer F, Kapsreiter M, Zenk J, Velegrakis GA, et al. Management of locally advanced laryngeal cancer. J Otolaryngol Head Neck Surg. 2014;43(1):4.
- Megwalu UC, Sikora AG. Survival outcomes in advanced laryngeal cancer. JAMA Otolaryngol Head Neck Surg. 2014;140(9):855–60.
- Talamini R, Bosetti C, La Vecchia C, Dal Maso L, Levi F, Bidoli E, et al. Combined effect of tobacco and alcohol on laryn-geal cancer risk: a case-control study. Cancer Causes Control. 2002;13:957-64.
- Moore CE, Wiatrak BJ, McClatchey KD, Koopmann CF, Thomas GR, Bradford CR, et al. High-risk human papillomavirus typesand squamous cell carcinoma in patients with respiratory papil-lomas. Otolaryngol Head Neck Surg. 1999;120:698-705.
- de Oliveira DE, Bacchi MM, Macarenco RS, Tagliarini JV, CordeiroRC, Bacchi CE. Human papillomavirus and Epstein-Barr virusinfection, p53 expression and cellular proliferation in laryngealcarcinoma. Am J Clin Pathol. 2006;126:284-93.
- Münger K, Baldwin A, Edwards EM, Hayakawa H. Mecha-nisms of human papillomavirus induced oncogenesis. J Virol. 2004;78:11451- 60.
- Halec G, Holzinger D, Schmitt M, Flechtenmacher C, Dyckhoff G, Lloveras B, et al. Biological evidence for a causal role of HPV16in a small fraction of laryngeal squamous cell carcinoma. Br J Cancer. 2013;109:172-83.
- Isayeva T, Li Y, Maswahu D, Brandwein-Gensler M. Humanpapillomavirus in non-oropharyngeal head and neck can-cers: a systematic literature review. Head Neck Pathol. 2012;6: 104- 20.
- Worden FP, Kumar B, Lee JS, Wolf GT, Cordell KG, Taylor JMG, et al. Chemoselection as a strategy for organ preservation in advanced oropharynx cancer: response and survival positively associated with HPV16 copy number. J Clin Oncol. 2008;26(19):3138-46.
- Ahmadi N, Ahmadi N, Chan MV, Huo YR, Sritharan N, Chin R. Laryngeal squamous cell carcinoma survival in the context of human papillomavirus: a systematic review and meta-analysis. Cureus. 2018;10(2):e2234.
- Dahm V, Haitel A, Kaider A, Stanisz I, Beer A, Lill C. Cancer stage and pack-years, but not p16 or HPV, are relevant for survival in hypopharyngeal and laryngeal squamous cell carcinomas. Eur Arch Oto-Rhino-Laryngol. 2018;275(7):1837-43.
- Siegel RL, Miller KD, Jemal A. Cancer statistics, 2019. CA Cancer J Clin. 2019;69(1):7-34.
- Xu Y, Liu S, Yi H, Wang J, Dong P, Li X, et al. Human papillomavirus infection in 674 chinese patients with laryngeal squamous cell carcinoma. Plos One. 2014;9:e115914.
- Salazar CR, Anayannis N, Smith RV, Wang Y, Haigentz M Jr, Garg M, et al. Combined p16 and human papillomavirus testing pre-dicts head and neck cancer survival. Int J Cancer. Head Neck Pathol. 2014;8:77-87.
- Shestakova A, Tarabay J, Burtsev A, Ibe I, Kim J, Chandan V, et al. Increased PD-L1 and p16 expression are common in oropharyngeal squamous cell carcinoma. Future Sci OA. 2021;7(9):FSO768.
- Li X, Gao L, Li H, Gao J, Yang Y, Zhou F, et all. Human papillomavirus infection and laryngeal cancer risk: a systematic review and meta-analysis. J Infect Dis. 2013;207(3):479-88.
- Dogantemur S, Ozdemir S, Uguz A, Surmelioglu O, Dagkiran M, Tarkan O, et all. Assessment of HPV 16, HPV 18, p16 expression in advanced stage laryngeal cancer patients and prognostic significance. Braz J Otorhinolaryngol. 2020;86(3):351-7.
- Allegra E, Bianco MR, Mignogna C, Caltabiano R, Grasso M, Puzzo L. Role of P16 Expression in the Prognosis of Patients With Laryngeal Cancer: A Single Retrospective Analysis. Cancer Control. 2021;28:10732748211033544.
- Hernandez BY, Goodman MT, Lynch CF, Cozen W, Unger ER, Steinau M, et all; HPV Typing of Cancer Workgroup. Human papillomavirus prevalence in invasive laryngeal cancer in the United States. PLoS One. 2014;9(12):e115931.
- Meshman J, Wang PC, Chin R, John MS, Abemayor E, Bhuta S, et all. Prognostic significance of p16 in squamous cell carcinoma of the larynx and hypopharynx. Am J Otolaryngol. 2017;38(1):31-7.
- Bussu F, Sali M, Gallus R, Vellone VG, Zannoni GF, Autorino R, et all. HPV infection in squamous cell carcinomas arising from different mucosal sites of the head and neck region. Is p16 immunohistochemistry a reliable surrogate marker? Br J Cancer. 2013;108(5):1157-62.
- Vazquez-Guillen JM, Palacios-Saucedo GC, Alanis-Valdez AY, Huerta-Escobedo A, Zavala-Pompa A, Rivera-Morales LG, et al. p16INK4a and pRb expression in laryngeal squamous cell carcinoma with and without infection by EBV or different genotypes of HPV: a retrospective study. Infect Agent Cancer. 2023;18(1):43.
- Sánchez Barrueco A, González Galán F, Villacampa Aubá JM, Díaz Tapia G, Fernández Hernández S, Martín-Arriscado Arroba C, et all. p16 Influence on laryngeal squamous cell carcinoma relapse and survival. Otolaryngol Head Neck Surg. 2019;160(6):1042-7.
- Young RJ, Urban D, Angel C, Corry J, Lyons B, Vallance N, et all. Frequency and prognostic significance of p16(INK4A) protein overexpression and transcriptionally active human papillomavirus infection in laryngeal squamous cell carcinoma. Br J Cancer. 2015;17;112(6):1098-104.
- Dahm V, Haitel A, Kaider A, Stanisz I, Beer A, Lill C. Cancer stage and pack-years, but not p16 or HPV, are relevant for survival in hypopharyngeal and laryngeal squamous cell carcinomas. Eur Arch Oto-Rhino-Laryngol. 2018;275(7):1837-43.