THE RELATIONSHIP BETWEEN TUMOR AND LYMPHADENOPATHY CT HISTOGRAM PARAMETERS AND TUMOR STAGE AND HPV STATUS IN HEAD AND NECK SQUAMOUS CELL CARCINOMA

Öz

OBJECTIVE: This study aimed to evaluate the association between computed tomography (CT) histogram parameters of the tumor and lymphadenopathy and tumor stage and Human papillomavirus (HPV) status in head and neck squamous cell carcinoma (HNSCC).
MATERIAL AND METHODS: Data archive and CT images from the ‘HNSCC’ study, which are publicly available on ‘The Cancer Imaging Archive’ website, were used in this study. Patients who had a pretreatment contrast-enhanced neck CT examination with a slice thickness of 1.3 mm and whose HPV status were known were included in the study. Histogram analysis was performed on 215 tumors and 197 lymphadenopathies. Tumor and lymphadenopathy boundaries, including cystic and necrotic areas, were manually drawn from a single axial CT slice where the lesion size was the largest. Then, histogram parameters (mean, variance, skewness, kurtosis, 1st percentile (P), 10th P, 50th P, 90th P, 99th P) were calculated from the corresponding areas. Histogram parameters were compared with T (tumor), N (lymph node), and TNM (tumor-lymph node-metastasis) stage and HPV status of tumors.
RESULTS: 178 males and 37 females were included in this study (median age 57 years). There were significant differences in mean, variance, 10th P, 50th P, 90th P, and 99th P values of the tumor and skewness value of lymphadenopathy between T stages (p: 0.05, 0.038, 0.032, 0.047, 0.046, 0.022 ve 0.008, respectively). We found that the 10th P value of the tumor was significantly higher in the N0 stage than in the N3 stage (p:0.028). There were no significant differences in histogram parameters between TNM stages (p:0.073-0.792). Variance and 50th P values of the tumor were significantly lower in HPV positive tumors than in HPV negatives (p: 0.035 ve 0.048, respectively).
CONCLUSIONS: CT histogram parameters showed significant differences between T stage, N stage, and HPV status in HNSCC. Variance value reflecting the heterogeneity was found higher in HPV negative tumors and high T stages.

Anahtar Kelimeler

• Head and neck squamous cell carcinoma
• Computed tomography
• Histogram analysis

BAŞ VE BOYUN SKUAMÖZ HÜCRELİ KANSERİNDE TÜMÖR VE LENFADENOPATİ BT HİSTOGRAM PARAMETRELERİ İLE TÜMÖR EVRESİ VE HPV DURUMU ARASINDAKİ İLİŞKİ

Öz

AMAÇ: Bu çalışmada baş ve boyun skuamöz hücreli kanserinde (BBSHK) tümör ve metastatik lenfadenopati bilgisayarlı tomografi (BT) histogram parametreleri ile tümör evresi ve Human papilloma virüs (HPV) durumu arasındaki ilişkinin araştırılması hedeflenmiştir.
GEREÇ VE YÖNTEM: Çalışmamızda ‘Kanser Görüntüleme Arşivi’ veri tabanında kayıtlı ‘Baş ve Boyun Skuamöz Hücreli Kanseri’ isimli çalışmaya ait anonimize veri seti ve bu çalışmaya kayıtlı olguların anonimize BT görüntüleri kullanılmıştır. Tedavi öncesi 1.3 mm kesit kalınlığında kontraslı boyun BT incelemesi bulunan ve HPV durumu bilinen olgular çalışmaya dahil edilmiştir. 215 tümör ve 197 lenfadenopatiden histogram analizi gerçekleştirilmiştir. Lezyonların en geniş boyuta ulaştığı aksiyel kesit belirlenerek bu kesitte lezyon sınırları nekrotik-kistik alanları da içerecek şekilde çizilmiş ve bu alan üzerinden histogram parameterleri [ortalama, varyans, çarpıklık, kurtozis, 1.persentil (P), 10.P, 50.P, 90.P ve 99.P] hesaplanmıştır. Histogram parametreleri ile tümörlerin T (tümör), N (lenf nodu) ve TNM (tümör-lenf nodu-metastaz) evresi ve HPV durumu karşılaştırılmıştır.
BULGULAR: Çalışmaya 178 erkek, 37 kadın olgu dahil edilmiştir (medyan yaş 57 yıl). Tümör histogram parametrelerinden ortalama değer, varyans, 10.P, 50.P, 90.P ve 99.P değerleri ile lenfadenopati histogram parametrelerinden çarpıklık değeri farklı T evreleri arasında istatistiksel anlamlı fark göstermiştir (p değerleri sırasıyla 0.05, 0.038, 0.032, 0.047, 0.046, 0.022 ve 0.008). N0 evre kanserlerin tümör 10.P değerinin N3 evre kanserlerden istatistiksel anlamlı yüksek olduğu bulunmuştur (p:0.028). Tümör ve lenfadenopatiye ait histogram parametrelerinden hiçbiri farklı TNM evreleri arasında istatistiksel anlamlı fark göstermemiştir (p değerleri 0.073-0.792). Tümör varyans değeri ve 50.P değeri HPV pozitif tümörlerde HPV negatif tümörlere göre istatistiksel anlamlı düşük bulunmuştur (p değerleri sırasıyla 0.035 ve 0.048).
SONUÇ: BT histogram parametreleri farklı T evresi, N evresi ve HPV durumuna sahip BBSHK arasında istatistiksel anlamlı fark göstermiştir. Heterojeniteyi gösteren varyans değeri T evresi yüksek tümörler ile HPV negatif tümörlerde daha yüksek bulunmuştur

Anahtar Kelimeler

• Baş ve boyun skuamöz hücre karsinomu
• Human papilloma virüs
• Bilgisayarlı tomografi
• Histogram analizi
• Head and neck squamous cell carcinoma
• Computed tomography
• Histogram analysis

Kaynakça

1. 1. Sung H, Ferlay J, Siegel RL, et al. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J Clin. 2021;71(3):209-49.
2. 2. Marur S, Forastiere AA. Head and Neck Squamous Cell Carcinoma: Update on Epidemiology, Diagnosis, and Treatment. Mayo Clin Proc. 2016;91(3):386-96.
3. 3. Zanoni DK, Patel SG, Shah JP. Changes in the 8th Edition of the American Joint Committee on Cancer (AJCC) Staging of Head and Neck Cancer: Rationale and Implications. Curr Oncol Rep. 2019;21(6):52.
4. 4. Lassen P, Primdahl H, Johansen J, et al. Impact of HPV-associated p16-expression on radiotherapy outcome in advanced oropharynx and non-oropharynx cancer. Radiother Oncol. 2014;113(3):310-6.
5. 5. Ang KK, Harris J, Wheeler R, et al. Human papillomavirus and survival of patients with oropharyngeal cancer. N Engl J Med. 2010;363(1):24-35.
6. 6. Cantrell SC, Peck BW, Li G, Wei Q, Sturgis EM, Ginsberg LE. Differences in imaging characteristics of HPV-positive and HPV-Negative oropharyngeal cancers: a blinded matched-pair analysis. AJNR Am J
7. Neuroradiol. 2013;34(10):2005-9.
8. 7. Chan MW, Yu E, Bartlett E, et al. Morphologic and topographic radiologic features of human papillomavirus-related and -unrelated oropharyngeal carcinoma. Head Neck. 2017;39(8):1524-34.

9. 8. Goldenberg D, Begum S, Westra WH, et al. Cystic lymph node metastasis in patients with head and neck cancer: An HPV-associated phenomenon. Head Neck. 2008;30(7):898-903.
10. 9. Augustin JG, Lepine C, Morini A, et al. HPV Detection in Head and Neck Squamous Cell Carcinomas: What Is the Issue? Front Oncol. 2020;10:1751.
11. 10. Forghani R, Chatterjee A, Reinhold C, et al. Head and neck squamous cell carcinoma: prediction of cervical lymph node metastasis by dual-energy CT texture analysis with machine learning. Eur Radiol. 2019;29(11):6172-81.
12. 11. Ahn SJ, Choi SH, Kim YJ, et al. Histogram analysis of apparent diffusion coefficient map of standard and high B-value diffusion MR imaging in head and neck squamous cell carcinoma: a correlation study with histological grade. Acad Radiol. 2012;19(10):1233-40.
13. 12. Dang M, Lysack JT, Wu T, et al. MRI texture analysis predicts p53 status in head and neck squamous cell carcinoma. AJNR Am J Neuroradiol. 2015;36(1):166-70.
14. 13. Buch K, Fujita A, Li B, Kawashima Y, Qureshi MM, Sakai O. Using Texture Analysis to Determine Human Papillomavirus Status of Oropharyngeal Squamous Cell Carcinomas on CT. AJNR Am J Neuroradiol. 2015;36(7):1343-8.
15. 14. Fujita A, Buch K, Li B, Kawashima Y, Qureshi MM, Sakai O. Difference Between HPV-Positive and HPV-Negative Non-Oropharyngeal Head and Neck Cancer: Texture Analysis Features on CT. J Comput Assist Tomogr. 2016;40(1):43-7.
16. 15. Huang C, Cintra M, Brennan K, et al. Development and validation of radiomic signatures of head and neck squamous cell carcinoma molecular features and subtypes. EBioMedicine. 2019;45:70-80.
17. 16. Leijenaar RT, Bogowicz M, Jochems A, et al. Development and validation of a radiomic signature to predict HPV (p16) status from standard CT imaging: a multicenter study. Br J Radiol. 2018;91(1086):20170498.
18. 17. Mukherjee P, Cintra M, Huang C, et al. CT-based Radiomic Signatures for Predicting Histopathologic Features in Head and Neck Squamous Cell Carcinoma. Radiol Imaging Cancer. 2020;2(3):e190039.
19. 18. Wu W, Ye J, Wang Q, Luo J, Xu S. CT-Based Radiomics Signature for the Preoperative Discrimination Between Head and Neck Squamous Cell Carcinoma Grades. Front Oncol. 2019;9:821.
20. 19. Zhu Y, Mohamed ASR, Lai SY, et al. Imaging-Genomic Study of Head and Neck Squamous Cell Carcinoma: Associations Between Radiomic Phenotypes and Genomic Mechanisms via Integration of The Cancer Genome Atlas and The Cancer Imaging Archive. JCO Clin Cancer Inform. 2019;3:1-9.
21. 20. Fujima N, Homma A, Harada T, et al. The utility of MRI histogram and texture analysis for the prediction of histological diagnosis in head and neck malignancies. Cancer Imaging. 2019;19(1):5.
22. 21. Ren J, Tian J, Yuan Y, et al. Magnetic resonance imaging based radiomics signature for the preoperative discrimination of stage I-II and III-IV head and neck squamous cell carcinoma. Eur J Radiol. 2018;106:1-6.
23. 22. Romeo V, Cuocolo R, Ricciardi C, et al. Prediction of Tumor Grade and Nodal Status in Oropharyngeal and Oral Cavity Squamous-cell Carcinoma Using a Radiomic Approach. Anticancer Res. 2020;40(1):271-80.
24. 23. Parmar C, Leijenaar RT, Grossmann P, et al. Radiomic feature clusters and prognostic signatures specific for Lung and Head & Neck cancer. Sci Rep. 2015;5:11044.
25. 24. Bogowicz M, Riesterer O, Ikenberg K, et al. Computed Tomography Radiomics Predicts HPV Status and Local Tumor Control After Definitive Radiochemotherapy in Head and Neck Squamous Cell Carcinoma. Int J Radiat Oncol Biol Phys. 2017;99(4):921-28.
26. 25. Yu K, Zhang Y, Yu Y, et al. Radiomic analysis in prediction of Human Papilloma Virus status. Clin Transl Radiat Oncol. 2017;7:49-54.
27. 26. Ranjbar S, Ning S, Zwart CM, et al. Computed Tomography-Based Texture Analysis to Determine Human Papillomavirus Status of Oropharyngeal Squamous Cell Carcinoma. J Comput Assist Tomogr. 2018;42(2):299-305.
28. 27. Mungai F, Verrone GB, Pietragalla M, et al. CT assessment of tumor heterogeneity and the potential for the prediction of human papillomavirus status in oropharyngeal squamous cell carcinoma. Radiol Med. 2019;124(9):804-11.
29. 28. Grossberg AJ, Mohamed ASR, Elhalawani H, et al. Imaging and clinical data archive for head and neck squamous cell carcinoma patients treated with radiotherapy. Sci Data. 2018;5:180173.
30. 29. Clark K, Vendt B, Smith K, et al. The Cancer Imaging Archive (TCIA): maintaining and operating a public information repository. J Digit Imaging. 2013;26(6):1045-57.
31. 30. Sethi S, Ali-Fehmi R, Franceschi S, et al. Characteristics and survival of head and neck cancer by HPV status: a cancer registry-based study. Int J Cancer. 2012;131(5):1179-86.
32. 31. Upile NS, Shaw RJ, Jones TM, et al. Squamous cell carcinoma of the head and neck outside the oropharynx is rarely human papillomavirus related. Laryngoscope. 2014;124(12):2739-44.
33. 32. El-Mofty SK, Zhang MQ, Davila RM. Histologic identification of human papillomavirus (HPV)-related squamous cell carcinoma in cervical lymph nodes: a reliable predictor of the site of an occult head and neck primary carcinoma. Head Neck Pathol. 2008;2(3):163-8.