Lymphatic Spread Patterns in HPV+ vs. HPV- Oropharyngeal Squamous Cell Carcinoma: A Multi-Center European Analysis
- 1UniversityHospital Zurich
Abstract
BackgroundHuman papillomavirus (HPV)-positive oropharyngeal squamous cell carcinoma (OPSCC) shows higher prevalence of lymph node metastases than HPV-negative OPSCC. It remains unclear whether HPV-positive and HPV-negative OPSCC differ in occult metastasis risk, which is relevant to personalize elective nodal treatment volumes.
MethodsWe performed a retrospective analysis of 780 untreated OPSCC patients from four European centers. Patterns of lymph node level involvement (LNLs I, II, III, IV, V, VII) were assessed using a consensus diagnosis integrating imaging (CT, MRI, PET) and pathological findings from surgically treated patients. Occult metastases were assessed in 288 surgical patients with paired clinical and pathological information.
ResultsHPV-positive patients more frequently presented with ipsilateral LNL II involvement, particularly in early T-stage disease (80.6% [75.6-84.8] vs. 54.8% [47.2-62.2]). However, the probability of downstream involvement in LNLs III and IV conditioned on upstream LNL involvement was similar between HPV-positive and HPV-negative patients. Similarly, contralateral involvement conditioned on midline extension of the primary tumor was similar. The overall proportion of occult metastases, defined as clinically false-negative LNLs divided by pathologically positive LNLs, was lower in HPV-positive patients (24.7% [19.7-30.1] vs. 48.7% [39.7-57.8]).
ConclusionsHPV-positive OPSCC showed higher prevalence of LNL involvement, especially in ipsilateral LNL II and early T-stage tumors. The data to directly compare occult metastasis risk has important limitations and does not allow definitive conclusions. However, the presented data suggests that higher prevalence likely does not translate into higher risk of occult metastases for the most common clinical diagnoses and therefore does not support larger elective nodal treatment volumes compared with HPV-negative tumors.
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- Clinical Profile and Survival of Oropharyngeal Squamous-Cell Carcinoma in a Region of Northern Spain with a Low HPV-Attributable Fraction: A Retrospective Cohort Study
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BibTeX
@misc{haas2026lymphatic,
title = {{Lymphatic Spread Patterns in HPV+ vs. HPV- Oropharyngeal Squamous Cell Carcinoma: A Multi-Center European Analysis}},
author = {Y. Perez Haas and R. Ludwig and E. L. Looman and P. Balermpas and S. Benavente and A. Schubert and D. Barbatei and L. Bauwens and O. Elicin and R. Giger and V. Gregoire and J. Unkelbach},
howpublished = {medRxiv},
year = {2026},
month = sep,
doi = {10.64898/2026.09.29.26364302},
url = {https://www.medrxiv.org/content/10.64898/2026.09.29.26364302v1},
note = {CC BY-NC-ND},
}
RIS
TY - UNPB
TI - Lymphatic Spread Patterns in HPV+ vs. HPV- Oropharyngeal Squamous Cell Carcinoma: A Multi-Center European Analysis
AU - Y. Perez Haas
AU - R. Ludwig
AU - E. L. Looman
AU - P. Balermpas
AU - S. Benavente
AU - A. Schubert
AU - D. Barbatei
AU - L. Bauwens
AU - O. Elicin
AU - R. Giger
AU - V. Gregoire
AU - J. Unkelbach
PY - 2026
DA - 2026/09/29
PB - medRxiv
DO - 10.64898/2026.09.29.26364302
UR - https://www.medrxiv.org/content/10.64898/2026.09.29.26364302v1
AB - BackgroundHuman papillomavirus (HPV)-positive oropharyngeal squamous cell carcinoma (OPSCC) shows higher prevalence of lymph node metastases than HPV-negative OPSCC. It remains unclear whether HPV-positive and HPV-negative OPSCC differ in occult metastasis risk, which is relevant to personalize elective nodal treatment volumes. MethodsWe performed a retrospective analysis of 780 untreated OPSCC patients from four European centers. Patterns of lymph node level involvement (LNLs I, II, III, IV, V, VII) were assessed using a consensus diagnosis integrating imaging (CT, MRI, PET) and pathological findings from surgically treated patients. Occult metastases were assessed in 288 surgical patients with paired clinical and pathological information. ResultsHPV-positive patients more frequently presented with ipsilateral LNL II involvement, particularly in early T-stage disease (80.6% [75.6-84.8] vs. 54.8% [47.2-62.2]). However, the probability of downstream involvement in LNLs III and IV conditioned on upstream LNL involvement was similar between HPV-positive and HPV-negative patients. Similarly, contralateral involvement conditioned on midline extension of the primary tumor was similar. The overall proportion of occult metastases, defined as clinically false-negative LNLs divided by pathologically positive LNLs, was lower in HPV-positive patients (24.7% [19.7-30.1] vs. 48.7% [39.7-57.8]). ConclusionsHPV-positive OPSCC showed higher prevalence of LNL involvement, especially in ipsilateral LNL II and early T-stage tumors. The data to directly compare occult metastasis risk has important limitations and does not allow definitive conclusions. However, the presented data suggests that higher prevalence likely does not translate into higher risk of occult metastases for the most common clinical diagnoses and therefore does not support larger elective nodal treatment volumes compared with HPV-negative tumors.
ER -