Key Points
Question
Is preoperative nodal core needle biopsy (CNB) associated with presence of extranodal extension (ENE) in final pathology analysis in patients with human papillomavirus (HPV)–associated oropharyngeal squamous cell carcinoma (OPSCC) targeted for primary surgical treatment?
Findings
In this cohort study of 106 patients with HPV-associated OPSCC targeted for primary surgery, preoperative nodal CNB was associated with pathologic ENE independent of preoperative node size.
Meaning
These findings support the possibility of an artifactual ENE component in patients with HPV-associated OPSCC who underwent preoperative nodal CNB.
This cohort study assesses whether preoperative nodal core needle biopsy is associated with presence of extranodal extension in final pathology findings among patients with human papillomavirus (HPV)–associated oropharyngeal squamous cell carcinoma targeted for primary surgical resection.
Abstract
Importance
Extranodal extension (ENE) is an adverse feature in human papillomavirus (HPV)–associated oropharyngeal squamous cell carcinoma (OPSCC) and is an indication for adjuvant treatment escalation. Preoperative core needle biopsy (CNB) may cause lymph node capsule disruption related to ENE development; however, evidence regarding this association in OPSCC is lacking.
Objective
To assess whether preoperative nodal CNB is associated with presence of ENE in final pathology findings among patients with HPV-associated OPSCC targeted for primary surgical resection.
Design, Setting, and Participants
This retrospective cohort study was conducted at a single academic tertiary care center from 2012 to 2022. All patients with OPSCC treated with transoral robotic surgery were assessed for eligibility, and primary surgical patients with HPV-associated OPSCC and node-positive disease confirmed on neck dissection were included in analyses. Data were analyzed from November 28, 2022, to May 21, 2023.
Exposure
Preoperative nodal CNB.
Main Outcomes and Measures
The primary outcome was presence of ENE in final pathology findings. Secondary outcomes included adjuvant chemotherapy and recurrence rates. Outcomes of interest were investigated against patient demographic, clinical, and pathologic features.
Results
Of 106 patients (mean [SD] age, 60.2 [10.9] years; 99 [93.4%] men) included in analyses, 23 patients (21.7%) underwent CNB. Mean (range) preoperative node size was 3.0 (0.9-6.0) cm. Pathologic node class was pN1 in 97 patients (91.5%) and pN2 in 9 patients (8.5%). A total of 49 patients (46.2%) had ENE identified in final pathology analysis. Of 94 patients who received adjuvant therapy, 58 (61.7%) underwent radiation therapy and 36 (38.3%) underwent chemoradiation therapy. There were 9 recurrences (8.5%). In univariate analysis, CNB was associated with ENE (odds ratio [OR], 2.70; 95% CI, 1.03-7.08), but there was no association in a multivariable model including pN class and preoperative node size (OR, 2.56; 95% CI, 0.97-7.27). Compared with pN1 class, pN2 class was associated with ENE (OR, 10.93; 95% CI, 1.32-90.80). There were no associations of ENE with preoperative node size, presence of cystic or necrotic nodes, fine needle aspiration, tobacco or alcohol exposure, pathologic T class, prior radiation, or age. Furthermore, use of CNB was not associated with macroscopic ENE, adjuvant chemotherapy, or recurrence.
Conclusions and Relevance
This cohort study of patients with HPV-associated OPSCC found that preoperative nodal CNB was strongly associated with ENE in final pathology, supporting the possibility of an artifactual ENE component in this population.
Introduction
The incidence of human papillomavirus (HPV)–associated oropharyngeal squamous cell carcinoma (OPSCC) has increased steadily in recent decades and now accounts for approximately 70% of all OPSCC in the US.1 Patients with OPSCC often present initially in the primary care setting with a persistent neck mass as their chief concern.2,3 Minimally invasive options for tissue diagnosis include fine needle aspiration (FNA) or core needle biopsy (CNB). A larger needle is required for CNB than for FNA, with sizes ranging from 14-gauge to 20-gauge (2.1 mm to 0.91 mm outer diameter) compared with at least 22-gauge (≤0.72 mm outer diameter) for FNA.4,5 In CNB, tissue is obtained with a spring-loaded cutting needle that cores out cellular material, while FNA relies on intrinsic capillary action of the needle.5 Core needle biopsy yields more tissue, allows for tumor architecture preservation, and facilitates accurate immunohistochemical analysis, including p16 testing, but theoretically carries an increased risk of either seeding the biopsy track with tumor cells directly or creating a pathway for subsequent tumor ingrowth.5,6
Extranodal extension (ENE) refers to growth of tumor cells from within a lymph node out into the perinodal connective tissue. A diagnosis of ENE is classified as microscopic when extension is 2 mm or less or macroscopic when extension is greater than 2 mm beyond the capsule.7,8 Among patients with upper aerodigestive tract cancers, including HPV-associated OPSCC, ENE is associated with increased distant disease recurrence rates and worse overall survival.9,10 The presence of ENE on final pathology is considered an adverse feature and is an indication to consider adding concurrent chemotherapy to adjuvant radiation in patients undergoing surgical treatment.9,10,11
In other cancer types, CNB has been associated with primary tumor or lymph node capsular disruption, as well as an increased rate of distant metastasis compared with FNA.12,13,14,15 However, the association between needle biopsy type and presence of ENE in OPSCC has not been fully explored in the literature. In this study, we examined the association between nodal CNB and presence of ENE in final pathology findings in a cohort of patients with HPV-associated OPSCC treated with primary surgical resection followed by adjuvant therapies at a single tertiary care academic center.
Methods
This cohort study was approved by the University of Iowa Institutional Review Board with a waiver of informed consent because of the retrospective nature of the review using existing data with no additional data or patient interaction needed. This study adhered to the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) reporting guideline.
We performed a retrospective review of patients with OPSCC who were treated at the University of Iowa Hospitals and Clinics from 2012 to 2022 and underwent transoral robotic surgery (TORS)–assisted resection and neck dissection during that period. Patients are offered TORS at our institution if their primary tumors are amenable to TORS exposure and resection with a realistic chance at negative surgical margins and they have no clinical evidence of ENE or other preoperative indications for adjuvant chemotherapy.
Eligible patients for this study were identified from our institutional tumor registry. Clinical notes, operative notes, preoperative imaging, radiology reports, pathology reports, and tumor registry data were reviewed. Patients with p16-negative or unknown p16 tumors were excluded. Patients who did not undergo neck dissection or who had node-negative disease in final pathology findings were also excluded. A diagram of study patient selection is detailed in the Figure.
Figure. Flowchart of Study Patient Selection.
OPSCC indicates oropharyngeal squamous cell carcinoma; TORS, transoral robotic surgery.
The primary outcome of interest was ENE identified on final pathologic analysis of neck dissection nodal specimens. Secondary outcomes included receipt of adjuvant chemotherapy and recurrence. The ENE was categorized into macroscopic or microscopic as classified on the surgical pathology report. Recurrence and adjuvant treatment data were obtained from the institutional tumor registry and verified through electronic health record (EHR) review. Recurrence was categorized into local, regional, or distant disease. Local recurrence was defined as return of cancer at or contiguous to the site of the original primary tumor before the study end date of March 7, 2022. The same period was used for regional and distant recurrence. To qualify as having regional or distant recurrence, patients had to be free of a simultaneous upper aerodigestive tract primary cancer.
Based on review of EHRs, patients were categorized as having undergone CNB or as not having CNB exposure. Patients who underwent both FNA and CNB were included in the CNB group. Potential confounding variables that we investigated included age at diagnosis, tobacco exposure, alcohol exposure, prior radiation history, preoperative node size and characteristics (cystic vs solid), and pathologic T- and N-classification (American Joint Committee on Cancer, 8th edition). Preoperative node size was measured as the greatest dimension of the largest cervical node on initial preoperative imaging. Patients were classified as having cystic or necrotic nodes if any lymph node was deemed cystic or necrotic on preoperative imaging by the radiology team. They were classified as having solid nodes if the radiology team found no cystic or necrotic nodes.
Statistical analysis was performed using SAS statistical software version 9.4 (SAS Institute). Odds ratios (ORs) and 95% CIs for associations between independent variables and the outcome variables were calculated by univariate logistic regression analysis. Independent variables associated with ENE along with those that might reasonably confound the association between CNB and ENE were then entered into a multivariate logistic regression model. P values were 2-sided, and statistical significance was set at P = .05. Data were analyzed from November 28, 2022, to May 21, 2023.
Results
Of 193 patients with OPSCC treated with TORS, 106 patients (mean [SD] age, 60.2 [10.9] years; 99 [93.4%] men) were included in analyses. Demographics, clinical characteristics, surgical pathology results, and adjuvant treatment regimens are described in Table 1. Most patients (72 patients [67.9%]) reported current or previous tobacco use, and 48 patients (45.3%) reported current or previous alcohol use. Only 3 patients (2.8%) had a history of prior head and neck radiation. The mean (range) size of the largest node on preoperative imaging was 3.0 (0.9-6.0) cm. Suspicious lymphadenopathy was purely solid on imaging in 37 patients (34.9%), while 69 patients (65.1%) presented with a cystic or necrotic node.
Table 1. Patient Demographic and Clinicopathologic Characteristics.
| Characteristic | Patients, No. (%) | |
|---|---|---|
| Core needle biopsy (n = 23) | No core needle biopsy (n = 83) | |
| Age, mean (SD), y | 62.7 (10.9) | 59.5 (9.7) |
| Gender | ||
| Men | 20 (87.0) | 79 (95.2) |
| Women | 3 (13.0) | 4 (4.8) |
| Carcinogen exposure | ||
| Active or history of tobacco | 17 (73.9) | 56 (67.5) |
| Active or history of alcohol | 7 (30.4) | 41 (49.4) |
| Prior head or neck radiation | 0 | 3 (3.6) |
| Node characteristics | ||
| Size, mean (SD), cm | 2.8 (1.0) | 3.0 (1.0) |
| Cystic or necrotic | 14 (60.9) | 55 (66.3) |
| Solid | 9 (39.1) | 28 (33.7) |
| Pathologic T class | ||
| T0 | 1 (4.3) | 3 (3.6) |
| T1 | 15 (65.2) | 43 (51.8) |
| T2 | 6 (26.1) | 35 (42.2) |
| T3 | 1 (4.3) | 2 (2.4) |
| Pathologic N class | ||
| N1 | 20 (87.0) | 77 (92.8) |
| N2 | 3 (13.0) | 6 (7.2) |
| ENE identified | 15 (65.2) | 34 (41.0) |
| Macroscopic | 11 (73.3) | 20 (58.8) |
| Microscopic | 4 (26.7) | 11 (32.4) |
| Not classified | 0 | 3 (8.8) |
| Adjuvant therapy | ||
| None | 4 (17.4) | 8 (9.6) |
| Radiation only | 9 (39.1) | 49 (59.0) |
| Chemoradiation | 10 (43.5) | 26 (31.3) |
Abbreviation: ENE, extranodal extension.
Fifty-eight patients (54.7%) underwent FNA and 18 patients (17.0%) underwent CNB. Five patients (4.7%) underwent both FNA and CNB, and 25 patients (23.6%) underwent either excisional biopsy or were diagnosed via primary site tissue sampling. All patients in the CNB group received their initial biopsies at community facilities prior to being evaluated at the University of Iowa. None of the referring clinicians explicitly requested CNB, but it was the initial biopsy method chosen by the performing clinicians in 21 of 23 patients (91.3%) who underwent CNB. The reason for initial CNB in these patients was not stated in biopsy procedure reports and could not be inferred from clinician notes. Only 2 patients who underwent CNB were reported to receive CNB due to an initial nondiagnostic FNA.
Pathologic neck staging was pN1 in 97 patients (91.5%) and pN2 in 9 patients (8.5%). Final pathology analysis reported ENE was present in 49 patients (46.2%). On surgical pathology analysis, 31 patients were identified to have macroscopic ENE, 15 patients had microscopic ENE, and 3 patients had unspecified ENE classifications. Twelve (11.3%) patients did not receive any adjuvant treatment. Of 94 patients who proceeded with adjuvant therapy, 58 (61.7%) underwent adjuvant radiation therapy and 36 (38.3%) underwent adjuvant chemoradiation therapy. Overall survival in our study population at the end of the study period was 87.7% (93 patients). There were 9 recurrences (8.5%), including 2 local recurrences, 3 regional recurrences, and 4 distant recurrences.
We did not find that CNB was preferentially selected for patients with cystic or necrotic nodes compared with solid nodes (OR, 0.79; 95% CI, 0.31-2.05) or with increasing preoperative node size (OR per 1-cm increase, 0.78; 95% CI, 0.49-1.26) (Table 2). In univariate analysis, CNB was associated with an increased likelihood of ENE in final pathology findings (OR, 2.70; 95% CI, 1.03-7.08). No association with ENE was found for FNA without CNB, preoperative size of the largest presenting node, or having cystic nodes on presentation. Pathologic N2 classification was associated with higher likelihood of ENE compared with pathologic N1 classification (OR, 10.93; 95% CI, 1.32-90.80). Tobacco exposure, alcohol exposure, pathologic T classification, prior radiation, and age were not associated with ENE. The multivariable model included pathologic N classification, CNB, and size of largest node, with the latter included due to the a priori consideration that CNB may have been more likely used for larger nodes. Multivariate analysis did not find an association between CNB and ENE (OR, 2.65; 95% CI, 0.97-7.27). Pathologic N classification remained independently associated with ENE (OR, 10.60; 95% CI, 1.25-90.10). There was no association with node size (OR, 1.05; 95% CI, 0.70-1.58), and node size did not confound the associations of CNB or pN class with ENE.
Table 2. Potential Risk Factors for ENE.
| Factor | Odds ratio (95% CI) | |
|---|---|---|
| Univariate | Multivariate | |
| CNB | 2.70 (1.03-7.08) | 2.65 (0.97-7.27) |
| FNA without core | 0.84 (0.32-2.16) | NA |
| Tobacco smoking | ||
| None | 1 [Reference] | NA |
| Current | 1.93 (0.68-5.42) | NA |
| Quit <10 y | 0.76 (0.22-2.72) | NA |
| Quit >10 y | 1.20 (0.46-3.16) | NA |
| Alcohol | ||
| None | 1 [Reference] | NA |
| Current | 1.43 (0.48-4.27) | NA |
| Quit <10 y | 0.67 (0.10-4.29) | NA |
| Quit >10 y | 0.45 (0.17-1.18) | NA |
| Prior head or neck radiation | 0.57 (0.05-6.52) | NA |
| Age, per 1-y increase | 1.01 (0.97-1.05) | NA |
| Pathologic T class | ||
| T3 | 6.00 (0.22-162.50) | NA |
| T2 | 2.59 (0.25-27.00) | NA |
| T1 | 2.61 (0.26-26.60) | NA |
| T0 | 1 [Reference] | NA |
| Pathologic class N2 (vs N1) | 10.93 (1.32-90.8) | 10.60 (1.25-90.10) |
| Cystic or necrotic node | 1.43 (0.64-3.20) | NA |
| Preoperative node size, per 1-cm increase | 0.99 (0.68-1.44) | 1.05 (0.70-1.58) |
Abbreviations: CNB, core needle biopsy; ENE, extranodal extension; FNA, fine needle aspiration; NA, not applicable.
Among 49 patients with ENE, CNB exposure was not associated with a higher likelihood of macroscopic ENE (OR, 1.21; 95% CI, 0.33-4.39) (Table 3). Patients who underwent CNB were not more likely to undergo chemotherapy compared with those who did not undergo CNB (OR, 1.69; 95% CI, 0.65-4.34). There was no association of CNB with recurrence (OR, 1.03; 95% CI, 0.20-5.35) (Table 3).
Table 3. Univariate Analysis Between Core Needle Biopsy and Outcome Variables.
| Factor | Patients, No. | Odds ratio (95% CI) | |
|---|---|---|---|
| Core needle biopsy (n = 23) | No core needle biopsy (n = 83) | ||
| ENE findings | |||
| ENE | 15 | 34 | 2.70 (1.03-7.08) |
| No ENE | 8 | 49 | 1 [Reference] |
| ENE size | |||
| Macroscopic | 11 | 20 | 1.21 (0.33-4.39) |
| Microscopic | 5 | 11 | 1 [Reference] |
| Adjuvant chemotherapy | |||
| Yes | 10 | 26 | 1.69 (0.65-4.34) |
| No | 13 | 57 | 1 [Reference] |
| Recurrence | |||
| Any | 2 | 7 | 1.03 (0.20-5.35) |
| No | 21 | 76 | 1 [Reference] |
Abbreviation: ENE, extranodal extension.
Discussion
In this cohort study, we investigated the association of cervical lymph node needle biopsy type with the presence of ENE in final pathology findings in patients with HPV-associated OPSCC treated with primary surgical resection. We found preoperative CNB to be associated with a higher likelihood of ENE in univariate analysis but not multivariate analysis, while preoperative node size, cystic nodes at presentation, FNA, age, prior carcinogen exposure, and pathologic T classification were not associated with ENE. Higher pathologic N classification was associated with ENE. Use of CNB was not significantly associated with larger or cystic nodes at presentation, macroscopic ENE (vs microscopic ENE), the addition of adjuvant chemotherapy, or recurrence rates.
The risk of iatrogenic tumor seeding or ingrowth along needle biopsy tracks has been a concern for almost a century.16 There is evidence that CNB carries a much higher risk of seeding compared with FNA in cancers throughout the body, although estimated incidence of seeding in head and neck lesions is extremely low for both biopsy methods.6 The large needle diameter and high velocity punctures delivered by conventional spring-loaded core biopsy tools are both factors implicated in the increased risk associated with CNB.6,17 Taking multiple passes with the biopsy needle has also been associated with increased seeding incidence.6 A 2002 case series by Douglas-Jones and Verghese13 reported 2 cases of papillary carcinoma of the breast in which artifactual extracapsular tumors were found on histological examination of excised specimens after preoperative CNB of the primary sites. A study by Claro et al12 found a significantly higher incidence of ENE in patients who underwent diagnostic percutaneous needle biopsy of lymph nodes in melanoma compared with those who underwent open excisional biopsy. Our findings regarding the risk of extranodal tumor extension in association with CNB in OPSCC cervical nodal disease concur with the trend seen in other cancer types, which, to our knowledge, has not been previously reported in the literature.
Due to correlation with increased distant disease recurrence and worse overall survival, ENE is considered a high-risk feature in HPV-associated OPSCC.7,9,10,18 Current National Comprehensive Cancer Network treatment guidelines recommend chemotherapy in addition to adjuvant radiation after upfront surgical resection when ENE is identified on surgical pathology. However, adjuvant chemotherapy causes significant acute and late toxic effects, and the survival benefit of adding chemotherapy to adjuvant regimens in patients with ENE has been called into question.19,20 The overall improved prognosis and longer life expectancy of patients with HPV-associated OPSCC magnifies the relative impact of adjuvant treatment–related toxic effects and has led to a call for treatment deescalation efforts in appropriate patients.21
Higher clinical N classification has been associated with increased odds of pathologic ENE in other studies.22,23 In our study, increased preoperative node size was not found to be associated with ENE on univariate analysis or in a multivariate model including CNB or number of positive nodes in final pathology findings, suggesting an association between CNB and ENE that is independent of clinical nodal disease burden. There was no association between preoperative node size and CNB, making it unlikely that larger nodes at presentation influenced initial biopsy choice. The association between pathologic N classification and ENE that we found is not surprising, as both are histopathologic features of more advanced regional disease. Given that preoperative CNB precedes both pathologic N and ENE and pathologic N and ENE are simultaneous findings in surgical pathology analysis, the association between pathologic N and ENE does not weaken or confound the CNB-ENE association. Additional studies with more diverse cohorts and a larger study population are necessary to investigate the exact interactions among pathologic N classification, ENE, and CNB in HPV-associated OPSCC.
While this study does not establish a causal relationship between CNB and ENE, our results support the possibility of an artifactual or iatrogenic component of ENE in patients who have undergone preoperative nodal CNB. If future studies confirm our findings, the surgical pathology findings of ENE for these patients may not be an accurate reflection of biologic tumor behavior, and thus conventional recommendations for adjuvant treatment escalation with concurrent chemotherapy may be too aggressive. We did not find CNB to be associated with increased regional or distant recurrence rates in our study population, suggesting that the associated ENE that we identified may not carry oncologic significance.
Limitations
This study has some limitations. The retrospective nature of this study and limited cohort size carry intrinsic biases in data collection and interpretation. Institutional-specific surgical eligibility criteria for TORS limit the generalizability of our results. Precise biopsy targets, the specific nodes positive for ENE, and ENE extent were not always defined in pathology reports; thus, we were unable to establish whether ENE in final pathology findings was identified in the same node that underwent preoperative CNB. Additionally, the number of passes performed to obtain needle biopsies was inconsistently reported in procedure notes and could not be included in our analysis. As many pathologic factors associated with prognosis in head and neck cancers are still being identified, we advocate for the implementation of standardized and specific surgical pathology reporting systems, both for improved clinical communication as well as for research interests. Future multi-institutional prospective studies are needed to better define the associations between preoperative CNB and nodal surgical pathology findings, as well as to establish the oncologic significance of these pathologic features.
Conclusions
The findings of this cohort study suggest preoperative CNB of cervical lymph nodes was associated with ENE in final pathology findings in patients with HPV-associated OPSCC, independent of preoperative lymph node size. Patients with HPV-associated OPSCC often have a good prognosis with a multidisciplinary approach. Additional research is needed to explore this association more thoroughly and establish its relevance in adjuvant treatment discussions.
Data Sharing Statement.
References
- 1.Roman BR, Aragones A. Epidemiology and incidence of HPV-related cancers of the head and neck. J Surg Oncol. 2021;124(6):920-922. doi: 10.1002/jso.26687 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 2.Khalid MB, Ting P, Pai A, et al. Initial presentation of human papillomavirus-related head and neck cancer: a retrospective review. Laryngoscope. 2019;129(4):877-882. doi: 10.1002/lary.27296 [DOI] [PubMed] [Google Scholar]
- 3.McIlwain WR, Sood AJ, Nguyen SA, Day TA. Initial symptoms in patients with HPV-positive and HPV-negative oropharyngeal cancer. JAMA Otolaryngol Head Neck Surg. 2014;140(5):441-447. doi: 10.1001/jamaoto.2014.141 [DOI] [PubMed] [Google Scholar]
- 4.Novoa E, Gürtler N, Arnoux A, Kraft M. Role of ultrasound-guided core-needle biopsy in the assessment of head and neck lesions: a meta-analysis and systematic review of the literature. Head Neck. 2012;34(10):1497-1503. doi: 10.1002/hed.21821 [DOI] [PubMed] [Google Scholar]
- 5.VanderLaan PA. Fine-needle aspiration and core needle biopsy: an update on 2 common minimally invasive tissue sampling modalities. Cancer Cytopathol. 2016;124(12):862-870. doi: 10.1002/cncy.21742 [DOI] [PubMed] [Google Scholar]
- 6.Shah KS, Ethunandan M. Tumour seeding after fine-needle aspiration and core biopsy of the head and neck—a systematic review. Br J Oral Maxillofac Surg. 2016;54(3):260-265. doi: 10.1016/j.bjoms.2016.01.004 [DOI] [PubMed] [Google Scholar]
- 7.Beltz A, Zimmer S, Michaelides I, et al. Significance of extranodal extension in surgically treated HPV-positive oropharyngeal carcinomas. Front Oncol. 2020;10:1394. doi: 10.3389/fonc.2020.01394 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 8.Bullock MJ, Beitler JJ, Carlson DL, et al. Data set for the reporting of nodal excisions and neck dissection specimens for head and neck tumors: explanations and recommendations of the guidelines from the International Collaboration on Cancer Reporting. Arch Pathol Lab Med. 2019;143(4):452-462. doi: 10.5858/arpa.2018-0421-SA [DOI] [PubMed] [Google Scholar]
- 9.Bauer E, Mazul A, Chernock R, et al. Extranodal extension is a strong prognosticator in HPV-positive oropharyngeal squamous cell carcinoma. Laryngoscope. 2020;130(4):939-945. doi: 10.1002/lary.28059 [DOI] [PubMed] [Google Scholar]
- 10.Benchetrit L, Torabi SJ, Givi B, Haughey B, Judson BL. Prognostic significance of extranodal extension in HPV-mediated oropharyngeal carcinoma: a systematic review and meta-analysis. Otolaryngol Head Neck Surg. 2021;164(4):720-732. doi: 10.1177/0194599820951176 [DOI] [PubMed] [Google Scholar]
- 11.National Comprehensive Cancer Network . NCCN clinical practice guidelines in oncology: head and neck cancers version 2. 2018. Accessed March 5, 2023. https://www.nccn.org/professionals/physician_gls/pdf/head-and-neck.pdf
- 12.Claro G, Meyer N, Meresse T, Gangloff D, Grolleau JL, Chaput B. Does needle biopsy cause an increased risk of extracapsular extension in the diagnosis of metastatic lymph node in melanoma? Int J Dermatol. 2018;57(4):410-416. doi: 10.1111/ijd.13936 [DOI] [PubMed] [Google Scholar]
- 13.Douglas-Jones AG, Verghese A. Diagnostic difficulty arising from displaced epithelium after core biopsy in intracystic papillary lesions of the breast. J Clin Pathol. 2002;55(10):780-783. doi: 10.1136/jcp.55.10.780 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 14.Fu Y, Guo F, Chen H, et al. Core needle biopsy promotes lung metastasis of breast cancer: an experimental study. Mol Clin Oncol. 2019;10(2):253-260. doi: 10.3892/mco.2018.1784 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 15.Sennerstam RB, Franzén BSH, Wiksell HOT, Auer GU. Core-needle biopsy of breast cancer is associated with a higher rate of distant metastases 5 to 15 years after diagnosis than FNA biopsy. Cancer Cytopathol. 2017;125(10):748-756. doi: 10.1002/cncy.21909 [DOI] [PubMed] [Google Scholar]
- 16.Martin HE, Ellis EB. Biopsy by needle puncture and aspiration. Ann Surg. 1930;92(2):169-181. doi: 10.1097/00000658-193008000-00002 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 17.Janssens JP, Rotenberg L, Sentis M, Motmans K, Schulz-Wendtland R. Caution with microbiopsies of the breast: displaced cancer cells and ballistics. Eur J Cancer Prev. 2006;15(6):471-473. doi: 10.1097/CEJ.0b013e3280126b77 [DOI] [PubMed] [Google Scholar]
- 18.Han M, Stanford-Moore GB, Larson AR, et al. Predictors of mortality in HPV-associated oropharynx carcinoma treated with surgery alone. Laryngoscope. 2020;130(7):E423-E435. doi: 10.1002/lary.28344 [DOI] [PubMed] [Google Scholar]
- 19.O’Neill CB, Baxi SS, Atoria CL, et al. Treatment-related toxicities in older adults with head and neck cancer: a population-based analysis. Cancer. 2015;121(12):2083-2089. doi: 10.1002/cncr.29262 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 20.An Y, Park HS, Kelly JR, et al. The prognostic value of extranodal extension in human papillomavirus-associated oropharyngeal squamous cell carcinoma. Cancer. 2017;123(14):2762-2772. doi: 10.1002/cncr.30598 [DOI] [PubMed] [Google Scholar]
- 21.Bigelow EO, Seiwert TY, Fakhry C. Deintensification of treatment for human papillomavirus-related oropharyngeal cancer: current state and future directions. Oral Oncol. 2020;105:104652. doi: 10.1016/j.oraloncology.2020.104652 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 22.Zebolsky AL, George E, Gulati A, et al. Risk of pathologic extranodal extension and other adverse features after transoral robotic surgery in patients with HPV-positive oropharynx cancer. JAMA Otolaryngol Head Neck Surg. 2021;147(12):1080-1088. doi: 10.1001/jamaoto.2021.2777 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 23.Ochoa E, Stanford-Moore G, Fakhry C, Ryan WR. Predicting adverse histopathology and need for postsurgical adjuvant therapy for human papilloma virus–associated oropharynx carcinoma. Otolaryngol Head Neck Surg. 2021;165(2):309-316. doi: 10.1177/0194599820982913 [DOI] [PubMed] [Google Scholar]
Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Supplementary Materials
Data Sharing Statement.
