The prognostic significance of the ‘Worst Pattern of Invasion’ in oral cancers−an international collaborative multicentre analysis
Worst pattern of invasion (WPOI) has been evaluated in many single-institute cohorts. Our goal was to perform a large multicentre evaluation of WPOI as a prognostic marker in oral squamous cell carcinoma (OSCC). Retrospective pathology data was collated from 14 institutions and compared with clinical outcome in 1374 OSCC patients with upfront curative resection. Most cases were of oral tongue (n = 645, 47%); T2 (33%) and N0 (59%). WPOI 1-3 frequency was 29.4%, WPOI 4 47% and WPOI 5 22%. On univariable analysis, the 3-year disease free survival (DFS) was 54.2% for WPOI 5 vs. 69.7% for WPOI 1-4 (p < 0.001). The locoregional control (LRC) was 68.9% vs 79.2% (p = 0.001), and overall survival (OS) 68.4% vs 83.8% (p < 0.001). On multivariable Cox-regression in the entire cohort, WPOI 4 or 5 was strongly correlated with other known poor prognostic factors and not an independent predictor of OS (HR 1.10, 95% CI 0.92-1.52), LRC or DFS. However, in early-stage (pT1-2 N0) patients treated with surgery alone without adjuvant radiotherapy, WPOI 5 was a robust independent predictor of DFS (HR 4.36, 95% CI 1.54-12.32, p = 0.006), OS (HR 3.69, 95% CI 1.23-11.1, p = 0.020) and LRC (HR 3.52, 95% CI 2.13-5.82, p <0.001) after applying inverse probability weighting to correct for selection bias. Furthermore, in the entire cohort of early-stage patients, interaction modeling showed that adjuvant radiotherapy significantly reduces the risk for both DFS and LRC for those with WPOI-5 (Interaction p = 0.002). Therefore, it may act as a predictive biomarker for the benefit of adjuvant radiotherapy. The prognostic and predictive role of WPOI-5 should be validated in prospective trials.
Authors
- Christina Wiedmer
- Cessal Thomas
- Shivani Sarkar
- K.R. Anila
- Reshma Kurian (ORCID: https://orcid.org/0000-0002-7179-6531)
- Shanthi Velusamy
- Akhila Gopakumar
- Pattatheyil Arun
- Shaji Thomas (ORCID: https://orcid.org/0000-0002-8454-208X)
- Poonam Abhay Elhence (ORCID: https://orcid.org/0000-0002-4660-389X)
- Anand Bardia (ORCID: https://orcid.org/0000-0003-1543-6133)
- Indranil Mallick (ORCID: https://orcid.org/0000-0002-5567-9204)
- Sanjoy Chatterjee (ORCID: https://orcid.org/0000-0001-7402-8645)
- Jenny Tung Hiong Lee (ORCID: https://orcid.org/0009-0004-7967-9278)
- Rajsekhar Shantappa
- Aanchal Kakkar
- Ruta Gupta
- Daphne Fonseca
- Nidhi Anand
- Indu Arun
- Jerry Z. Liu
- Megha Shantveer Uppin
- Paromita Roy
- Ritu Srivastava
- Sahithi Shilpa Arya
- Tsu-Hui Hubert Low
- Meera Thomas
- Rekha V. Kumar
- Meenakshi Kamboj
- Shantveer G. Uppin
- Suvradeep Mitra
- Amanjit Bal
- Mark Urken
- R. Chitra
- Pramod Kumar Pamu
- Munita Bal
- Shubhada V. Kane
- Margaret Brandwein Weber
- Sunil Pasricha
- Asawari Patil
- Jeevan Ram Vishnoi
- Kapila Manikantan
- Deepa Nair
- Nuzhat Husain
Institutions
- Nizam's Institute of Medical Sciences (IN)
- Christian Medical College, Vellore (IN)
- Homi Bhabha National Institute (IN)
- All India Institute of Medical Sciences Jodhpur (IN)
- Royal Prince Alfred Hospital (AU)
- Regional Cancer Center, Thiruvananthapuram (IN)
- Jaslok Hospital (IN)
- Tata Medical Center (IN)
- Rajiv Gandhi Cancer Institute and Research Centre (IN)
- Basavatarakam Indo American Cancer Hospital and Research Institute (IN)
- Cancer Hospital and Research Institute (IN)
- Dr. Ram Manohar Lohia Institute of Medical Sciences (IN)
- Post Graduate Institute of Medical Education and Research (IN)
- All India Institute of Medical Sciences (IN)
- Icahn School of Medicine at Mount Sinai (US)
- Macquarie University (AU)
Publication Details
- Journal
- Oral Oncology
- Published
- 2026-02-03
- DOI
- https://doi.org/10.1016/j.oraloncology.2026.107874
- Primary Topic
- Head and Neck Cancer Studies
- Type
- article
- Field-Weighted Citation Impact
- 0.00