To determine the frequency, associated factors, and prognosis of clinicopathologic stage discrepancy in oropharyngeal squamous cell carcinoma (OPSCC).
Study Design
Retrospective study using a national database.
Setting
National Cancer Database.
Subjects and Methods
Cases of OPSCC diagnosed between January 1, 2004, and December 31, 2013, with full clinical and pathologic staging information available were identified. Demographic, clinicopathologic, and treatment variables associated with overall stage discrepancy were identified by multivariate logistic regression analysis.
Results
In total, 7731 cases of OPSCC were identified. Overall stage discrepancy was present in 30.2% of cases (21.9% upstaging, 8.2% downstaging). A total of 13.1% of cases were T-upstaged, and 10.5% of cases were T-downstaged; 22.9% of cases were N-upstaged, and 8.6% of cases were N-downstaged. Upstaging by overall stage was associated with a high Charlson-Deyo score, high tumor grade, number of lymph nodes examined, and increasing tumor size. No factors were positively associated with downstaging. High tumor grade was negatively associated with downstaging. For stage II, III, and IVA tumors, upstaging was associated with poorer OS.
Conclusion
Clinicopathologic stage discrepancy is common in OPSCC and is likely attributable to insensitive clinical staging techniques as well as to intrinsic tumor biologic properties. Upstaging is associated with poorer prognosis, which is likely due to advancement of disease.
HelmanSNSchwedhelmTKadakiaSWangYSchiffBASmithRV.Transoral robotic surgery in oropharyngeal carcinoma. Arch Pathol Lab Med. 2015;139:1389-1397.
2.
SturgisEMCinciripiniPM.Trends in head and neck cancer incidence in relation to smoking prevalence: an emerging epidemic of human papillomavirus–associated cancers?Cancer. 2007;110:1429-1435.
3.
WarnakulasuriyaS.Global epidemiology of oral and oropharyngeal cancer. Oral Oncol. 2009;45:309-316.
4.
EisbruchAHarrisJGardenASet al. Multi-institutional trial of accelerated hypofractionated intensity-modulated radiation therapy for early-stage oropharyngeal cancer (RTOG 00-22). Int J Radiat Oncol Biol Phys. 2010;76:1333-1338.
5.
SooKCTanEHWeeJet al. Surgery and adjuvant radiotherapy vs concurrent chemoradiotherapy in stage III/IV nonmetastatic squamous cell head and neck cancer: a randomised comparison. Br J Cancer. 2005;93:279-286.
6.
ThariatJAngKKAllenPKet al. Prediction of neck dissection requirement after definitive radiotherapy for head-and-neck squamous cell carcinoma. Int J Radiat Oncol Biol Phys. 2012;82:e367-e374.
7.
SandulacheVCOwTJDaramSPet al. Residual nodal disease in patients with advanced-stage oropharyngeal squamous cell carcinoma treated with definitive radiation therapy and posttreatment neck dissection: association with locoregional recurrence, distant metastasis, and decreased survival. Head Neck. 2013;35:1454-1460.
8.
HanaiNKawakitaDOzawaTHirakawaHKodairaTHasegawaY.Neck dissection after chemoradiotherapy for oropharyngeal and hypopharyngeal cancer: the correlation between cervical lymph node metastasis and prognosis. Int J Clin Oncol. 2014;19:30-37.
9.
KresnikEMikoschPGallowitschHJet al. Evaluation of head and neck cancer with 18F-FDG PET: a comparison with conventional methods. Eur J Nucl Med. 2001;28:816-821.
10.
DahlstromKRCalzadaGHanbyJDet al. An evolution in demographics, treatment, and outcomes of oropharyngeal cancer at a major cancer center. Cancer. 2013;119:81-89.
11.
RossGShoaibTSoutarDSet al. The use of sentinel node biopsy to upstage the clinically N0 neck in head and neck cancer. Arch Otolaryngol Head Neck Surg. 2002;128:1287-1291.
12.
BottcherADommerichSSanderSet al. Nodal yield of neck dissections and influence on outcome in laryngectomized patients. Eur Arch Otorhinolaryngol. 2016;273:3321-3329.
13.
KordačPKalfeřtDSmatanováKet al. Discordance between clinical and pathological TNM classifications in patients with oropharyngeal cancer—influence on treatment and prognosis [in Czech]. Klin Onkol. 2015;29:122-126.
14.
BilimoriaKYStewartAKWinchesterDPKoCY.The National Cancer Data Base: a powerful initiative to improve cancer care in the United States. Ann Surg Oncol. 2008;15:683-690.
15.
FedewaSAWardEMStewartAKEdgeSB.Delays in adjuvant chemotherapy treatment among patients with breast cancer are more likely in African American and Hispanic populations: a national cohort study 2004-2006. J Clin Oncol. 2010;28:4135-4141.
16.
GardnerKHHillDEWrightACet al. Upstaging from melanoma in situ to invasive melanoma on the head and neck after complete surgical resection. Dermatol Surg. 2015;41:1122-1125.
17.
AlkureishiLWRossGLShoaibTet al. Does tumor depth affect nodal upstaging in squamous cell carcinoma of the head and neck?Laryngoscope. 2008;118:629-634.
18.
RossGLSoutarDSMacDonaldDGShoaibTCamilleriIGRobertsonAG.Improved staging of cervical metastases in clinically node-negative patients with head and neck squamous cell carcinoma. Ann Surg Oncol. 2004;11:213-218.
19.
KowalskiLPCarvalhoAL.Influence of time delay and clinical upstaging in the prognosis of head and neck cancer. Oral Oncol. 2001;37:94-98.
20.
DidierDPhilippeL.Characteristics of patients with upstaging by sentinel lymph node biopsy of the N0 neck in head and neck cancer. J Cancer Ther. 2011;2:285-287.
21.
GreenbergJSEl NaggarAKMoVRobertsDMyersJN.Disparity in pathologic and clinical lymph node staging in oral tongue carcinoma: implication for therapeutic decision making. Cancer. 2003;98:508-515.
22.
KochWMRidgeJAForastiereAManolaJ.Comparison of clinical and pathological staging in head and neck squamous cell carcinoma: results from Intergroup Study ECOG 4393/RTOG 9614. Arch Otolaryngol Head Neck Surg. 2009;135:851-858.
23.
BironVLO’ConnellDASeikalyH.The impact of clinical versus pathological staging in oral cavity carcinoma—a multi-institutional analysis of survival. J Otolaryngol Head Neck Surg. 2013;42:28.
24.
ShettyDJayadeBVJoshiSKGopalkrishnanK.Accuracy of palpation, ultrasonography, and computed tomography in the evaluation of metastatic cervical lymph nodes in head and neck cancer. Indian J Dent. 2015;6:121-124.
25.
WoolgarJABeirneJCVaughanEDLewis-JonesHGScottJBrownJS.Correlation of histopathologic findings with clinical and radiologic assessments of cervical lymph-node metastases in oral cancer. Int J Oral Maxillofac Surg. 1995;24:30-37.
26.
HaberalIÇelikHGöçmenHAkmansuHYörükMÖzeriC.Which is important in the evaluation of metastatic lymph nodes in head and neck cancer: palpation, ultrasonography, or computed tomography?Otolaryngol Head Neck Surg. 2004;130:197-201.
27.
LiaoLJLoWCHsuWLWangCTLaiMS.Detection of cervical lymph node metastasis in head and neck cancer patients with clinically N0 neck—a meta-analysis comparing different imaging modalities. BMC Cancer. 2012;12:236.
28.
KubicekGJChampCFoghSet al. FDG-PET staging and importance of lymph node SUV in head and neck cancer. Head Neck Oncol. 2010;2:19.
29.
PennI.Immunosuppression and cancer: importance in head and neck surgery. Arch Otolaryngol. 1975;101:667-670.
30.
PurginaBPantanowitzLSeethalaRR.A review of carcinomas arising in the head and neck region in HIV-positive patients. Patholog Res Int. 2011;2011:469150.
31.
BeachlerDCD’SouzaG.Oral HPV infection and head and neck cancers in HIV-infected individuals. Curr Opin Oncol. 2013;25:503-510.
32.
TongCCKaoJSikoraAG.Recognizing and reversing the immunosuppressive tumor microenvironment of head and neck cancer. Immunol Res. 2012;54:266-274.
33.
LinJLaiJBielMAXuYChenL.Immunosuppressive microenvironment in head and neck cancer. Contemporary Issues in Head and Neck Cancer Management. InTech; 2015;1:59-66.
34.
TsengKSLinCLinYSWengSF.Risk of head and neck cancer in patients with diabetes mellitus: a retrospective cohort study in Taiwan. JAMA Otolaryngol Head Neck Surg. 2014;140:746-753.
35.
Stott-MillerMChenCChuangSCet al. History of diabetes and risk of head and neck cancer: a pooled analysis from the international head and neck cancer epidemiology consortium. Cancer Epidemiol Biomarkers Prev. 2012;21:294-304.
36.
RosadoPChengHTWuCMWeiFC.Influence of diabetes mellitus on postoperative complications and failure in head and neck free flap reconstruction: a systematic review and meta-analysis. Head Neck. 2015;37:615-618.
HusainZAChenTCorsoCDet al. A comparison of prognostic ability of staging systems for human papillomavirus–related oropharyngeal squamous cell carcinoma. JAMA Oncol. 2017;3:358-365.
39.
KeaneFKChenYHNevilleBAet al. Changing prognostic significance of tumor stage and nodal stage in patients with squamous cell carcinoma of the oropharynx in the human papillomavirus era. Cancer. 2015;121:2594-2602.
40.
MarurSD’SouzaGWestraWHForastiereAA.HPV-associated head and neck cancer: a virus-related cancer epidemic. Lancet Oncol. 2010;11:781-789.
41.
HafkampHCManniJHaesevoetsAet al. Marked differences in survival rate between smokers and nonsmokers with HPV 16–associated tonsillar carcinomas. Int J Cancer. 2008;122:2656-2664.
42.
FakhryCWestraWHLiSet al. Improved survival of patients with human papillomavirus–positive head and neck squamous cell carcinoma in a prospective clinical trial. J Natl Cancer Inst. 2008;100:261-269.
43.
LydiattWMPatelSGO’SullivanBet al. Head and neck cancers—major changes in the American Joint Committee on cancer eighth edition cancer staging manual. CA Cancer J Clin. 2017;67:122-137.
44.
GrayPJLinCCJemalAet al. Clinical-pathologic stage discrepancy in bladder cancer patients treated with radical cystectomy: results from the National Cancer Data Base. Int J Radiat Oncol Biol Phys. 2014;88:1048-1056.
45.
BottMJPatelAPCrabtreeTDet al. Pathologic upstaging in patients undergoing resection for stage I non–small cell lung cancer: are there modifiable predictors?Ann Thorac Surg. 2015;100:2048-2053.
46.
RobertsTJColevasADHaraWHolsingerFCOakley-GirvanIDiviV.Number of positive nodes is superior to the lymph node ratio and American Joint Committee on Cancer N staging for the prognosis of surgically treated head and neck squamous cell carcinomas. Cancer. 2016;122:1388-1397.
47.
EbrahimiAGilZAmitMet al. Comparison of the American Joint Committee on Cancer N1 versus N2a nodal categories for predicting survival and recurrence in patients with oral cancer: time to acknowledge an arbitrary distinction and modify the system. Head Neck. 2016;38:135-139.
48.
NoorlagRBoeveKWitjesMJet al. Amplification and protein overexpression of cyclin D1: predictor of occult nodal metastasis in early oral cancer. Head Neck. 2017;39:326-333.
49.
TakesRPBaatenburgDeJongRJAllesMJet al. Markers for nodal metastasis in head and neck squamous cell cancer. Arch Otolaryngol Head Neck Surg. 2002;128:512-518.
50.
BuchbenderCHeusnerTALauensteinTCBockischAAntochG.Oncologic PET/MRI, part 1: tumors of the brain, head and neck, chest, abdomen, and pelvis. J Nucl Med. 2012;53:928-938.
51.
KimSGFriedmanKPatelSHagiwaraM.Potential role of PET/MRI for imaging metastatic lymph nodes in head and neck cancer. AJR Am J Roentgenol. 2016;207:248-256.
52.
PlatzekIBeuthien-BaumannBSchneiderMet al. PET/MRI in head and neck cancer: initial experience. Eur J Nucl Med Mol Imaging. 2013;40:6-11.
53.
von BuchwaldCBildeAShoaibTRossG. Sentinel node biopsy: the technique and the feasibility in head and neck cancer. ORL J Otorhinolaryngol Relat Spec. 2002;64:268-274.
54.
HoftSMauneSMuhleCet al. Sentinel lymph-node biopsy in head and neck cancer. Br J Cancer. 2004;91:124-128.
55.
CoughlinARestoVA.Oral cavity squamous cell carcinoma and the clinically N0 neck: the past, present, and future of sentinel lymph node biopsy. Curr Oncol Rep. 2010;12:129-135.
56.
MunroAJ.An overview of randomised controlled trials of adjuvant chemotherapy in head and neck cancer. Br J Cancer. 1995;71:83-91.
57.
El-SayedSNelsonN.Adjuvant and adjunctive chemotherapy in the management of squamous cell carcinoma of the head and neck region: a meta-analysis of prospective and randomized trials. J Clin Oncol. 1996;14:838-847.
58.
PignonJPBourhisJDomengeCDesigneL.Chemotherapy added to locoregional treatment for head and neck squamous-cell carcinoma: three meta-analyses of updated individual data. MACH-NC Collaborative Group. Meta-Analysis of Chemotherapy on Head and Neck Cancer. Lancet. 2000;355:949-955.
