Research Article| Volume 42, ISSUE 12, P1863-1868, August 2006

Meta-analysis of the prognostic significance of perinodal spread in head and neck squamous cell carcinomas (HNSCC) patients


      To assess the risk factor of capsular rupture for individual prognosis and potential therapeutic decision making, the present meta-analysis elaborated the prognostic significance of perinodal spread in a large group of patients suffering from head and neck squamous cell carcinomas (HNSCC). A review of the published literature was conducted, and fixed and random effects models were applied for estimation of the summarised odds ratio and 95% confidence intervals, including a test for homogeneity of the odds ratios. Study methodology allowed the enrollment of only nine studies of 115 published papers. Excluded studies lacked regarding primary tumour location, number and location of lymph node metastases, values on five-year survival, or adequate follow-up data. A summarised odds ratio of 2.7 leads to the conclusion that perinodal spread negatively impacts the five-year survival. The lower confidence limit of more than 2 also supports the concept that perinodal spread significantly reduces (doubled risk) the five-year-survival. These results support the conclusion that perinodal spread is a significant adverse risk factor for survival in patients with HNSCC.


      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'


      Subscribe to European Journal of Cancer
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect


        • Layland M.K.
        • Sessions D.G.
        • Lenox J.
        The influence of lymph node metastasis in the treatment of squamous cell carcinoma of the oral cavity, oropharynx, larynx, and hypopharynx: N0 versus N+.
        Laryngoscope. 2005; 115: 629-639
        • Toker C.
        Some observations on the deposition of metastatic carcinoma within cervical lymph nodes.
        Cancer. 1963; 16: 364-374
        • Carter R.L.
        • Barr L.C.
        • O’Brien C.J.
        • et al.
        Transcapsular spread of metastatic squamous cell carcinoma from cervical lymph nodes.
        Am J Surg. 1985; 150: 495-499
        • Jose J.
        • Coatesworth A.P.
        • MacLennan K.
        Cervical metastases in upper aerodigestive tract squamous cell carcinoma: histopathologic analysis and reporting.
        Head Neck. 2003; 25: 194-197
        • Brasilino de Carvalho M.
        Quantitative analysis of the extent of extracapsular invasion and its prognostic significance: a prospective study of 170 cases of carcinoma of the larynx and hypopharynx.
        Head Neck. 1998; 20: 16-21
        • Carter R.L.
        • Bliss J.M.
        • Soo K.-C.
        • et al.
        Radical neck dissections for squamous carcinomas: pathological findings and their clinical implications with particular reference to transcapsular spread.
        Int J Radiat Oncol Biol Phys. 1987; 13: 825-832
        • Carter R.L.
        The pathologist’s appraisal of neck dissections.
        Eur Arch Otorhinolaryngol. 1993; 250: 429-431
        • Snow G.B.
        • Annyas A.A.
        • Van Slooten E.A.
        • et al.
        Prognostic factors of neck node metastases.
        Clin Otolaryngol. 1982; 7: 185-192
        • Snyderman N.L.
        • Johnson J.T.
        • Schramm V.L.
        • et al.
        Extracapsular spread of carcinoma in cervical lymph nodes. Impact upon survival in patients with carcinoma of the supraglottic larynx.
        Cancer. 1985; 56: 1597-1599
        • Boysen M.
        • Lovdal O.
        • Natvig K.
        • et al.
        Combined radiotherapy and surgery in the treatment of neck node metastases from squamous cell carcinoma of the head and neck.
        Acta Oncol. 1992; 31: 455-460
        • Jose J.
        • Coatesworth A.P.
        • Johnston C.
        • et al.
        Cervical node metastases in squamous cell carcinoma of the upper aerodigestive tract: the significance of extracapsular spread and soft tissue deposits.
        Head Neck. 2003; 25: 451-456
        • Kokemüller H.
        • Brachvogel P.
        • Eckhardt A.
        • et al.
        Effectiveness of neck dissection in metastasizing mouth carcinoma. Uni- and multivariate analysis of factors of influence.
        Mund Kiefer Gesichtschir. 2002; 6: 91-97
        • Cole I.
        • Hughes L.
        The relationship of cervical lymph node metastases to primary sites of carcinoma of the upper aerodigestive tract: a pathological study.
        Aust NZ J Surg. 1997; 67: 860-865
        • Whitehead A.
        • Whitehead J.
        A general parametric approach to the meta-analysis of randomized clinical trials.
        Stat Med. 1991; 10: 1665-1677
        • Zelen M.
        The analysis of several 2 × 2 contingency tables.
        Biometrika. 1971; 58: 129-137
        • Mehta C.R.
        • Patel N.R.
        • Gray R.
        On computing an exact confidence interval for the common odds ratio in several 2 × 2 contingency tables.
        J Am Stat Assoc. 1985; 80: 969-973
        • Andersen P.E.
        • Warren F.
        • Spiro J.
        • et al.
        Results of selective neck dissection in management of the node-positive neck.
        Arch Otolaryngol Head Neck Surg. 2002; 128: 1180-1184
        • Hirabayashi H.
        • Koshii K.
        • Uno K.
        • et al.
        Extracapsular spread of squamous cell carcinoma in neck lymph nodes: prognostic factor of laryngeal cancer.
        Laryngoscope. 1991; 101: 502-506
        • Mamelle G.
        • Pampurik J.
        • Luboinski B.
        • et al.
        Lymph node prognostic factors in head and neck squamous cell carcinomas.
        Am J Surg. 1994; 168: 494-498
        • Myers J.N.
        • Greenberg J.S.
        • Mo V.
        • et al.
        Extracapsular spread. A significant predictor of treatment failure in patients with squamous cell carcinoma of the tongue.
        Cancer. 2001; 92: 3030-3036
        • Pinsolle J.
        • Pinsolle V.
        • Majoufre C.
        • et al.
        Prognostic value of histologic findings in neck dissections for squamous cell carcinoma.
        Arch Otolaryngol Head Neck Surg. 1997; 123: 145-148
        • Shingaki S.
        • Nomura T.
        • Takada M.
        • et al.
        The impact of extranodal spread of lymph node metastases in patients with oral cancer.
        Int J Oral Maxillofac Surg. 1999; 28: 228-279
        • Steinhart H.
        • Schroeder H.G.
        • Buchta B.
        • et al.
        Prognostic significance of extra-capsular invasion in cervical lymph node metastases of squamous epithelial carcinoma.
        Laryngorhinootologie. 1994; 73: 620-625
        • Woolgar J.A.
        • Rogers S.N.
        • Lowe D.
        • et al.
        Cervical lymph node metastasis in oral cancer: the importance of even microscopic extracapsular spread.
        Oral Oncol. 2003; 39: 130-137
        • Willis R.A.
        Epidermoid carcinoma of the head and neck, with special reference to metastasis.
        J Pathol Bacteriol. 1930; 33: 501-526
        • Bennett S.H.
        • Futrell J.W.
        • Roth J.A.
        • et al.
        Prognostic significance of histologic host response in cancer of the larynx or hypopharynx.
        Cancer. 1971; 28: 1255-1265
        • Wenzel S.
        • Kehrl W.
        • Bräsen J.-H.
        • et al.
        Ein neues Schema zur Beurteilung des metastatischen Lymphknotenbefalls beim Plattenepithelkarzinom im HNO- Gebiet.
        Laryngorhinootologie. 1998; 77: 657-662
        • Greenberg J.S.
        • Fowler R.
        • Gomez J.
        • et al.
        Extent of extracapsular spread (a critical prognosticator in oral tongue cancer).
        Cancer. 2003; 97: 1464-1470