Patterns of Nodal Metastases and Predictors of Occult Disease in HPV‐Associated Oropharynx Cancer

Abstract

Objective For human papilloma virus–associated oropharynx squamous cell carcinoma (HPV+ OPSCC), we evaluated the distribution of neck-level lymph node (LN) metastasis, based on postsurgical histopathology, and the incidence of and risk factors for occult LN metastases, as these patterns need clarification for this newer cancer subset. Study Design Retrospective cohort study. Setting National Cancer Database (NCDB). Methods We analyzed 2358 patients in the NCDB with HPV+ OPSCC who underwent neck dissection (ND) from 2010 to 2015. Incidence and distribution of LN metastases were calculated for neck levels I to V. Variables associated with occult LN metastasis were assessed by multivariate logistic regression. Results In therapeutic NDs (n = 1935), the following proportions of positive LNs were found: level I, 9.0% (n = 175); level II, 81.0% (n = 1568); level III, 29.6% (n = 573); level IV, 11.9% (n = 230); and level V, 4.9% (n = 95). In elective NDs (n = 423), occult-positive LNs were found in 35.8% (n = 152), with the following proportions by level: level I, 3.3% (n = 14); level II, 26.9% (n = 114); level III, 8.7% (n = 37); level IV, 4.0% (n = 17); and level V, 0.2% (n = 1). The presence of occult LNs was independently associated with a Charlson-Deyo score of 1 (odds ratio, 2.26; 95% CI, 1.18-4.31; P = .014) and lymphovascular invasion (odds ratio, 5.91; 95% CI, 3.21-11.18; P < .001). Occult LN metastases were not significantly associated with pT classification, primary site, or number of LNs resected. Conclusion For HPV+ OPSCC, occult nodal disease is common. Therapeutic NDs should encompass at least levels II, III, and IV and possibly I, whereas elective NDs could possibly encompass levels II and III. Level of Evidence 4.

Level IV neck dissection in cN0 HPV-negative oropharyngeal squamous cell carcinoma: A retrospective cohort study

“…Recently, focus has been on HPV-positive OPSCC due to its increasing incidence in Western countries; the majority of cases in the United States are potentially HPV positive, particularly among recent birth cohorts, perhaps resulting from changes in sexual behaviors. (9)(10)(11)(12). The majority of OPSCCs in some regions, such as China, are still HPV negative (13,14).…”

“…For patients who undergo END, only 4.0% (17/423) have occult lymph node metastasis at level IV. Hence, the authors considered that therapeutic neck dissection should encompass at least level II, III, and IV and that END encompassing level II-III is su cient for adequate pathologic staging and treatment of HPV-positive OPSCC(10) Nonetheless, research on level IV neck dissection in cN0 OPSCC remains controversial. Evidence to date largely relates to the distribution of cervical lymph node metastasis based on observational studies.…”

Rate of atypical nodal metastases in surgically treated HPV‐associated oropharyngeal squamous cell carcinoma

“…Current guidance recommends concurrent ipsilateral neck dissection of levels II–IV in all patients undergoing lateralized primary tumor surgical resection for OPSCC, regardless of HPV status 7 . Selective neck dissection (ND) in levels II–IV has been found to provide excellent disease control with low morbidity 8,9 . Cervical nodal levels I and V have demonstrated low (<10%) rates of positive cervical lymph nodes in this population 9 and thus are routinely excluded 10 .…”

“…Selective neck dissection (ND) in levels II–IV has been found to provide excellent disease control with low morbidity 8,9 . Cervical nodal levels I and V have demonstrated low (<10%) rates of positive cervical lymph nodes in this population 9 and thus are routinely excluded 10 . Recent studies have suggested that excision of levels II and III alone may be sufficient treatment in this patient population, particularly for those patients without clinical evidence of nodal disease 9,11 …”

“…10 Recent studies have suggested that excision of levels II and III alone may be sufficient treatment in this patient population, particularly for those patients without clinical evidence of nodal disease. 9,11 Despite advances in understanding differences in patterns of nodal involvement in HPV+ OPSCC tumors, the rates of atypical noncontiguous metastases (pathologic evidence of nodal disease in level II and a metastatic node in a noncontiguous level) or atypical skip metastases (pathologic lymph node(s) in the neck with the absence of disease in level II) have not been well described. 9,12,13 Similar to the concept of skip metastases for oral cavity SCC, 14 understanding the rates of atypical nodal and skip metastases in OPSCC may help deescalate elective NDs without compromising oncologic outcomes.…”