Correlation of PET-CT nodal SUVmax with p16 positivity in oropharyngeal squamous cell carcinoma

Journal of Otolaryngology-Head & Neck Surgery

Vincent L. Biron²  Hadi Seikaly¹  Jeffrey Harris¹  Daniel A. O’Connell¹  Tim Cooper¹  Han Zhang¹  Caroline C. Jeffery¹  Jessica Clark¹ 

[1] Faculty of Medicine and Dentistry, Department of Surgery, Division of Otolaryngology-Head and Neck Surgery, University of Alberta, Edmonton, Alberta, Canada;University of Alberta, Otolaryngology-Head and Neck Surgery, 1E4, Walter Mackenzie Centre, University of Alberta Hospital, 8440-112St, Edmonton T6G 2B7, Alberta, Canada

关键词: Human papillomavirus;    p16;    Standard uptake value;    Positron emission tomography;    Oropharyngeal cancer;   

Others  :  1225631
DOI  :  10.1186/s40463-015-0091-5

 received in 2015-06-04, accepted in 2015-09-02,  发布年份 2015

【 摘 要 】

Background

The incidence of human papillomavirus (HPV)-related oropharyngeal squamous cell carcinoma (OPSCC) has been rising in recent years. Given the clinical impact of HPV/p16 positivity in OPSCC, identifying surrogate markers of this disease early in the diagnostic work-up of these patients could improve patient care.

Methods

Demographic, pathologic, staging and PET-CT data from patients diagnosed with OPSCC from 2009–2014 were obtained from a prospectively collected provincial cancer registry. Tumor HPV/p16 status was correlated to the maximum standard uptake value (SUVmax) of the primary tumor and cervical nodes. Comparisons of means and multinomial regression models were used to determine associations between p16 status and SUVmax. A diagnostic odds ratio was calculated using a cut off value for predicting HPV/p16 positivity based on nodal SUVmax.

Results

PET-CT and HPV/p16 data was obtained for 65 patients treated surgically for OPSCC. Significantly higher nodal SUVmax was associated with HPV/p16 positive nodes (SUVmax 10.8 vs 7.9). No significant differences were seen between HPV/p16 positive vs negative primary tumor SUVmax (10.3 vs 13.7). In combination with other clinical parameters, higher nodal SUVmax was highly correlated with HPV/p16 positivity.

Conclusion

Elevated nodal SUVmax is a significant predictor of HPV/p16 positive disease.

【 授权许可】

   
2015 Clark et al.

【 图 表 】

Fig. 1.

Fig. 2.

【 参考文献 】

• [1]Hocking JS, Stein A, Conway EL, Regan D, Grulich A, Law M, Brotherton JML. Head and neck cancer in Australia between 1982 and 2005 show increasing incidence of potentially HPV-associated oropharyngeal cancers. Br J Cancer. 2011; 104:886-91.
• [2]Marur S, D’Souza G, Westra WH, Forastiere AA. HPV-associated head and neck cancer: a virus-related cancer epidemic. Lancet Oncol. 2010; 11:781-9.
• [3]Westra WH. The changing face of head and neck cancer in the 21st century: the impact of HPV on the epidemiology and pathology of oral cancer. Head Neck Pathol. 2009; 3:78-81.
• [4]Ang KK, Harris J, Wheeler R, Weber R, Rosenthal DI, Nguyen-Tân PF, Westra WH, Chung CH, Jordan RC, Lu C, Kim H, Axelrod R, Silverman CC, Redmond KP, Gillison ML. Human papillomavirus and survival of patients with oropharyngeal cancer. N Engl J Med. 2010; 363:24-35.
• [5]Gillison ML, Zhang Q, Jordan R, Xiao W, Westra WH, Trotti A, Spencer S, Harris J, Chung CH, Ang KK. Tobacco smoking and increased risk of death and progression for patients with p16-positive and p16-negative oropharyngeal cancer. J Clin Oncol. 2012; 30:2102-11.
• [6]Andrews E, Seaman WT, Webster-Cyriaque J. Oropharyngeal carcinoma in non-smokers and non-drinkers: a role for HPV. Oral Oncol. 2009; 45:486-91.
• [7]D’Souza G, Kreimer AR, Viscidi R, Pawlita M, Fakhry C, Koch WM, Westra WH, Gillison ML. Case–control study of human papillomavirus and oropharyngeal cancer. N Engl J Med. 2007; 356:1944-56.
• [8]Kumar B, Cordell KG, Lee JS, Worden FP, Prince ME, Tran HH, Wolf GT, Urba SG, Chepeha DB, Teknos TN, Eisbruch A, Tsien CI, Taylor JMG, D’Silva NJ, Yang K, Kurnit DM, Bauer JA, Bradford CR, Carey TE. EGFR, p16, HPV Titer, Bcl-xL and p53, sex, and smoking as indicators of response to therapy and survival in oropharyngeal cancer. J Clin Oncol. 2008; 26:3128-37.
• [9]Biron VLV, Mohamed AA, Hendzel MJM, Underhill DDA, Seikaly HH. Epigenetic differences between human papillomavirus-positive and -negative oropharyngeal squamous cell carcinomas. J Otolaryngol Head Neck Surg. 2012; 41 Suppl 1:S65-70.
• [10]van Kempen PM, Noorlag R, Braunius WW, Stegeman I, Willems SM, Grolman W. Differences in methylation profiles between HPV-positive and HPV-negative oropharynx squamous cell carcinoma: A systematic review. Epigenetics. 2014;9(2):194-203.
• [11]Cooper T, Biron V, Adam B, Klimowicz AC, Puttagunta L, Seikaly H. Prognostic utility of basaloid differentiation in oropharyngeal cancer. J Otolaryngol Head Neck Surg. 2013; 42:57. BioMed Central Full Text
• [12]Xu CC, Biron VL, Puttagunta L, Seikaly H. HPV Status and second primary tumours in Oropharyngeal Squamous Cell Carcinoma. J Otolaryngol Head Neck Surg. 2013; 42:36. BioMed Central Full Text
• [13]Seikaly H, Biron VL, Zhang H, O’Connell DA, Côté DWJ, Ansari K et al. The role of primary surgery in the treatment of advanced oropharyngeal cancer. Head Neck 2015. doi:10.1002/hed.24042.
• [14]Pfister DG, Ang K-K, Brizel DM, Burtness BA, Busse PM, Caudell JJ, Cmelak AJ, Colevas AD, Dunphy F, Eisele DW, Gilbert J, Gillison ML, Haddad RI, Haughey BH, Hicks WL, Hitchcock YJ, Kies MS, Lydiatt WM, Maghami E, Martins R, McCaffrey T, Mittal BB, Pinto HA, Ridge JA, Samant S, Schuller DE, Shah JP, Spencer S, Weber RS, Wolf GT et al.. Head and neck cancers, version 2.2013. Featured updates to the NCCN guidelines. J Natl Compr Canc Netw. 2013; 11:917-23.
• [15]Pentenero M, Cistaro A, Brusa M, Ferraris MM, Pezzuto C, Carnino R, Colombini E, Valentini MC, Giovanella L, Spriano G, Gandolfo S. Accuracy of 18 F-FDG-PET/CT for staging of oral squamous cell carcinoma. Head Neck. 2008; 30:1488-96.
• [16]Kurien G, Hu J, Harris J, Seikaly H. Cost-effectiveness of positron emission tomography/computed tomography in the management of advanced head and neck cancer. J Otolaryngol Head Neck Surg. 2011; 40:468-72.
• [17]Muylle K, Castaigne C, Flamen P. 18F-fluoro-2-deoxy-D-glucose positron emission tomographic imaging: recent developments in head and neck cancer. Curr Opin Oncol. 2005; 17:249-53.
• [18]Yoon DY, Hwang HS, Chang SK, Rho Y-S, Ahn HY, Kim JH, Lee IJ. CT, MR, US,18F-FDG PET/CT, and their combined use for the assessment of cervical lymph node metastases in squamous cell carcinoma of the head and neck. Eur Radiol. 2009; 19:634-42.
• [19]Lin DT, Cohen SM, Coppit GL, Burkey BB. Squamous cell carcinoma of the oropharynx and hypopharynx. Otolaryngol Clin North Am. 2005; 38:59-74.
• [20]Corey AS, Hudgins PA. Radiographic imaging of human papillomavirus related carcinomas of the oropharynx. Head Neck Pathol. 2012; 6 Suppl 1:S25-40.
• [21]Hoshikawa H, Yamamoto Y, Mori T, Kishino T, Fukumura T, Samukawa Y, Mori N, Nishiyama Y. Predictive value of SUV-based parameters derived from pre-treatment (18)F-FLT PET/CT for short-term outcome with head and neck cancers. Ann Nucl Med. 2014; 28:1020-6.
• [22]Arenz A, Ziemann F, Mayer C, Wittig A, Dreffke K, Preising S, Wagner S, Klussmann JP, Engenhart-Cabillic R, Wittekindt C. Increased radiosensitivity of HPV-positive head and neck cancer cell lines due to cell cycle dysregulation and induction of apoptosis. Strahlenther Onkol. 2014; 190:839-46.
• [23]Ziemann F, Arenz A, Preising S, Wittekindt C, Klussmann JP, Engenhart-Cabillic R, Wittig A. Increased sensitivity of HPV-positive head and neck cancer cell lines to x-irradiation ± Cisplatin due to decreased expression of E6 and E7 oncoproteins and enhanced apoptosis. Am J Cancer Res. 2015; 5:1017-31.
• [24]Kendi ATK, Magliocca K, Corey A, Nickleach DC, Galt J, Higgins K, Beitler JJ, El-Deiry MW, Wadsworth JT, Hudgins PA, Saba NF, Schuster DM. Do 18F-FDG PET/CT parameters in oropharyngeal and oral cavity squamous cell carcinomas indicate HPV status? Clin Nucl Med. 2015; 40:e196-200.
• [25]Tahari AK, Alluri KC, Quon H, Koch W, Wahl RL, Subramaniam RM. FDG PET/CT imaging of oropharyngeal squamous cell carcinoma: characteristics of human papillomavirus-positive and -negative tumors. Clin Nucl Med. 2014; 39:225-31.
• [26]Joo Y-H, Yoo I-R, Cho K-J, Park J-O, Nam I-C, Kim M-S. Preoperative 18F-FDG PET/CT and high-risk HPV in patients with oropharyngeal squamous cell carcinoma. Head Neck. 2014; 36:323-7.
• [27]O Connell D, Seikaly H, Murphy R, Fung C, Cooper T, Knox A, Scrimger R, Deutschmann M, Harris JR. Primary surgery versus chemoradiotherapy for advanced oropharyngeal cancers: a longitudinal population study. J Otolaryngol Head Neck Surg. 2013; 42:31. BioMed Central Full Text
• [28]Lau HY, Brar S, Klimowicz AC, Petrillo SK, Hao D, Brockton NT, Kong CS, Lees-Miller SP, Magliocco AM. Prognostic significance of p16 in locally advanced squamous cell carcinoma of the head and neck treated with concurrent cisplatin and radiotherapy. Head Neck. 2011; 33:251-6.
• [29]Begum S, Gillison ML, Ansari-Lari MA, Shah K, Westra WH. Detection of human papillomavirus in cervical lymph nodes: a highly effective strategy for localizing site of tumor origin. Clin Cancer Res. 2003; 9:6469-75.
• [30]Ho T, Zahurak M, Koch WM. Prognostic significance of presentation-to-diagnosis interval in patients with oropharyngeal carcinoma. Arch Otolaryngol Head Neck Surg. 2004; 130:45-51.
• [31]Fakhry C, Westra WH, Li S, Cmelak A, Ridge JA, Pinto H, Forastiere A, Gillison ML. Improved survival of patients with human papillomavirus-positive head and neck squamous cell carcinoma in a prospective clinical trial. J Natl Cancer Inst. 2008; 100:261-9.
• [32]Schmalbach CE, Miller FR. Occult primary head and neck carcinoma. Curr Oncol Rep. 2007; 9:139-46.
• [33]Mehta V, Johnson P, Tassler A, Kim S, Ferris RL, Nance M, Johnson JT, Duvvuri U. A new paradigm for the diagnosis and management of unknown primary tumors of the head and neck: a role for transoral robotic surgery. Laryngoscope. 2013; 123:146-51.
• [34]Karni RJ, Rich JT, Sinha P, Haughey BH. Transoral laser microsurgery: a new approach for unknown primaries of the head and neck. Laryngoscope. 2011; 121:1194-201.