September23, Unitedkingdom  2021 


Abstract Volume: 2 Issue: 2 ISSN:

Worst Pattern of Invasion: An Emerging Trend

                 Dr. Sachender Pal Singh*, Dr. Karan Chanchlani1, Dr. Gaurav Jaswal2

1. Consultant Radiation Oncologist, Optimus Oncology, Solapur Cancer Centre, Maharashtra, India

2. Department of Oncology, Consultant and In-charge, OncoLife Care Cancer Center, Chiplun, Maharashtra, India.,

Corresponding Author:  Dr. Sachender Pal Singh, Consultant Head and Neck Oncosurgeon, HCG Cancer Hospital, Ranchi, Editor MAR Oncology Journal

Copy Right: © 2021 Sachender Pal Singh. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Received Date: July 28, 2021

Published date: August 01, 2021

DOI: 10.1027/maroy.2021.130

Worst Pattern of Invasion: An Emerging Trend

Although we have experienced great deal of advancement in technology and guidelines, the 5year disease-specific survival has remained unchanged in early head & neck squamous cell carcinoma (SCC). When local surgery is used alone, up to 25% (stage I) and 37% (stage II) of patients with low-stage tumors develop local recurrence and/or regional lymph node metastasis during follow-up, associated with disease-related mortality1.Upwards of 30% such early-stage diseases have a high risk of regional metastasis2,3. This portends the problem of whether to proceed with an elective neck dissection, which can amount to overtreatment for many patients. According to D’Cruz et al3, 8 patients would need to be treated with elective neck dissection to prevent one death, and four patients would need to be treated to prevent one nodal relapse. Elective nodal radiotherapy (RT) in undissected cases can be considered but this also comes along with its own long term toxicity and morbidity. Moreover, regardless of a clear margin, the treatment failure rate for early-stage oral cavity squamous cell carcinoma is in the range of 10–40%4. These numbers force us to ponder about some parameter which could redefine guidelines and optimize them further. Amongst the emerging factors are tumor budding, lymphocytic interface and pattern of invasion at the tumor front.

Despite the inherent differences in tumor biology, contemporary practices for early-stage oral cavity squamous cell carcinoma continues to be surgical resection and often with no adjuvant therapy5. The definitive indications for adjuvant RT are close/positive margins and positive lymphnode status. Various other “soft” criteria are considered to judge the aggressiveness of tumor biology and include lymphovascular embolism (LVE), perineural invasion (PNI), grade of the tumor and depth of Invasion (DOI) to mention among the few. Traditionally, the grade of the tumor was considered to be the most predominant parameter defining treatment approach. However, the histologic grading of the deep invasive front of oral carcinomas had been shown to correlate more accurately with survival6,7.

Pattern of invasion (POI) is of 5 types out of which POI 1,2 & 3 comes under non-aggressive category and POI 4 & 5 are defined as aggressive. Brandwein-Gansler et al, proposed a scoring system (HRS) comprising of the sum of the specimen Lymphocytic Host Response (LHR), Worst Pattern of Invasion (WPOI) and PNI8,9. Various studies have validated and corroborated the impact of HRS score in prognostication. However, certain contrasting studies have failed to correlate HRS as a prognostic index but have validated WPOI as an independent prognostic marker for locoregional recurrence and death10,11. Suresh at al12 reported that oral SCCs with poorly differentiated invasive fronts showed localized low levels of expression of E-cadherin and increased incidence of lymph node metastases. The histologic pattern of invasion, a reflection of cell cohesion, correlates with in vitro markers of malignancy such as loss of contact inhibition, tumor cell motility, and secretion of proteolytic enzymes13.Worst POI has been found to be strongly associated with mortality14 and several studies have previously confirmed the relationship of unfavorable WPOI with poor prognosis in oral SCC15,16,17.Recently, a correlation between worst pattern of invasion type 5 (WPOI-5) and occult cervical metastases has been demonstrated18. Extratumoral PNI, and angiolymphatic invasion also count as WPOI-519. WPOI has been validated on multivariate analysis in oral tumors, specifically in low stage tumors20. It is an emerging trend amongst the researchers and looks promising. Even AJCC Cancer Staging Manual, 8th edition, guidelines have emphasized for the reporting of WPOI-5.

WPOI appears to be significant  if DOI<4mm21. For DOI >/=4mm, there is a significant risk of locoregional failure and death and  is more likely to be associated with other high risk factors like WPOI=5, PNI etc. As such, these patients are often considered for adjuvant treatment irrespective of margin and nodal status. Lastly, there may be a correlation between Biopsy pattern of invasion (BPOI) and the subsequent histological WPOI and DOI. Whether, BPOI can predict WPOI and DOI >/= 4mm and modify surgical decision making while addressing the primary tumor surgically needs to be further explored and validated.

To conclude, as it is well known that most aggressive cells reside at the invasive front of tumors, pattern of invasion could serve as an individual prognostic marker. WPOI alone or in combination with other histological factors it may justify the adjuvant radiotherapy/chemoradiotherapy in early as well as advanced oral cavity squamous cell carcinoma. Moreover, it can be a guide to select patient for neck dissection in early-stage tongue carcinoma with depth of invasion <4mm and therefore may not need to do neck dissections on each and every patient decreasing the morbidity of the treatment. Additionally, at this point of time we need to find out what could be the best possible course of action for patients with worst pattern of invasion 4 and 5 and no other high-risk factors. Whether such patients could benefit simply from addition of adjuvant radiotherapy to treatment protocol, or could this disease be so aggressive that adjuvant radiotherapy will have no impact on outcome and we may need to consider for adjuvant chemo-radiotherapy or even a change in surgical approach altogether. It also needs to be explored in tumors with DOI>/= 4mm, whether WPOI contributes to additional biological aggressiveness and affects the outcomes, thereby building the case for escalating adjuvant treatment. The logical next step would be to take all these points into consideration and conduct a multi-arm prospective randomized controlled trial.



1. Sessions DG, Spector GJ, Lenox J, et al. Analysis of treatment results for oral tongue cancer. Laryngoscope. 2002;112:616–25.

2. Layland MK, Sessions DG, 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(4):629–639. PMID: 15805872

3. D’Cruz AK, Vaish R, Kapre N, Dandekar M, Gupta S, Hawaldar R, et al. Elective versus therapeutic neck dissection in node-negative oral cancer. N Engl J Med 2015; 373(6):521–529. 1056/NEJMoa1506007 PMID: 26027881.

4. Khafif RA, Gelbfish GA, Tepper P, et al. Elective radical dissection in epidermoid cancer of the head and neck: a retrospective analysis of 853 cases of mouth, pharynx, and larynx cancer. Cancer. 1991;67:67–71.

5. Sutton DN, Brown JS, Rogers SN, et al. The prognostic implications of the surgical margin in oral squamous cell carcinoma. Int J Oral Maxillofac Surg 2003;32:30–34.

6. Yamamoto E, Miyakawa A, Kohama G. Mode of invasion and lymph node metastasis in squamous cell carcinoma of the oral cavity. Head Neck Surg 1984; 6:938-47.

7. Bryne M, Koppang HS, Lilleng R, Kjaerheim A. Malignancy grading of the deep invasive margins of oral squamous cell carcinomas has high prognostic value. ] Pafhol 1992; 166:375-81.

8. Brandwein-Gensler M, Teixeira MS, Lewis CM, et al. Oral squamous cell carcinoma: histologic risk assessment, but not margin status, is strongly predictive of local disease free and overall survival. Am J SurgPathol. 2005;29(2):167–78.

9. Brandwein–Gensler M, Smith RV, Wang B, et al. Validation of the histologic risk model in a new patient cohort with primary head and neck squamous cell carcinoma. Am J SurgPathol 2010;34:676–688.

10. Almangush et al Depth of invasion, tumor budding, and worst pattern of invasion: Prognostic indicators in early-stage oral tongue cancer. Head and Neck 2014.

11. Almangush A, Bello IO, Coletta RD, et al. For early-stage oral tongue cancer, depth of invasion and worst pattern of invasion are the strongest pathological predictors for locoregional recurrence and mortality. Virchows Arch. 2015;467(1):39-46.

12. Suresh TN, Hemalatha A, Harendra Kumar ML, Azeem Mohiyuddin SM. Evaluation of histomorphological and immunohistochemical parameters as biomarkers of cervical lymph node metastasis in squamous cell carcinoma of oral cavity: A retrospective study. J Oral MaxillofacPathol. 2015;19(1):18-24.

13. Crissman JD. Tumor-host interactions as prognostic factors in the histologic assessment of carcinomas. Pathol Ann 1986;21:29-52.

14. Almangush A et al. Depth of invasion, tumor budding, and worst pattern of invasion: Prognostic indicators. HEAD & NECK—DOI 10.1002/HED JUNE 2014, 811-818.

15. Sland TM, Brusevold IJ, Koppang HS, Schenck K, Bryne M. Nerve growth factor receptor (p75 NTR) and pattern of invasion predict poor prognosis in oral squamous cell carcinoma. Histopathology 2008;53:62–72.

16. Chang YC, Nieh S, Chen SF, Jao SW, Lin YL, Fu E. Invasive pattern grading score designed as an independent prognostic indicator in oral squamous cell carcinoma. Histopathology 2010;57:295–303.

17. Dissanayaka WL, Pitiyage G, Kumarasiri PV, Liyanage RL, Dias KD, Tilakaratne WM. Clinical and histopathologic parameters in survival of oral squamous cell carcinoma. Oral Surg Oral Med Oral Pathol Oral Radiol2012;113:518–525.

18. Velosa C, Shi Q, Stevens TM, Chiosea SI, Purgina B, Carroll W, Rosenthal E, Morlandt A, Loree T, Brandwein-Weber MS (2017) Worst pattern of invasion and occult cervical metastases for oral squamous carcinoma. Head Neck.

19. Ridge JA, Lydiatt WM, Patel SG, et al. Lip and oral cavity. In: Amin MB, ed. AJCC Cancer StagingManual. 8th ed. New York, NY: Springer; 2017.

20. Protocol for the examination of specimens from patients with cancers of the lip and oral cavity. College of American Pathologist. Version: LipOralCavity

21. Larson et al. Beyond Depth of Invasion: Adverse Pathologic Tumor Features in Early Oral Tongue Squamous Cell Carcinoma. 2019, Laryngoscope.