Comparison of Worst Pattern of Invasion with Other Histopathological Prognostic Indicators in Oral Cavity Squamous Cell Carcinoma: A Cohort Study from Regional Cancer Centre, Thiruvananthapuram, Kerala, India

Impact of Depth of Invasion Tumor Budding and Worst Pattern of Invasion on Clinical Outcome in Post-Operative Oral Cavity Squamous Cell Carcinoma

Oral cavity squamous cell carcinoma (OCSCC) is a well-recognized malignancy of the head and neck. Studies on patients with early-stage oral cancer have shown that they develop locally recurring and/or regional lymph node metastasis, which results in disease-associated mortality. Thus, early-stage oral cancer does not always present good prognoses. The present study aimed to determine the efficacy of using worst pattern of invasion (WPOI) and other histopathological features, such as prognostic factors in OCSCC, and analyze the impact of resection margin status and histopathological prognostic indicators on local recurrence (LR) and overall survival (OS) in patients with OCSCC. A retrospective cohort study was conducted by reviewing the charts of 63 patients with OCSCC treated with primary surgery at King Abdulaziz University Hospital between 2012 and 2019. An author and an experienced pathologist reviewed pathology slides. Associations of histopathological factors, including differentiation, stage, lymphovascular invasion, extracapsular extension, perineural invasion (PNI), WPOI and surgical margins, with LR or disease-free survival (DFS) were evaluated. Univariate analysis identified WPOI and PNI, and multivariate analysis identified the WPOI as predictive factors for LR and DFS. Kaplan-Meier analysis identified the WPOI and PNI as predictive factors for OS and WPOI as a predictive factor for DFS. Therefore, it may be concluded that WPOI and PNI are significant independent prognostic factors for local tumor control and DFS in patients with OCSCC.

Worst pattern of invasion in oral squamous cell carcinoma is an independent prognostic factor.

The Indications for Elective Neck Dissection in T1N0M0 Oral Cavity Squamous Cell Carcinoma

BackgroundTumour stroma ratio (TSR) has recently been introduced as a promising prognostic parameter in oral cavity cancers. However, the correlation between TSR and histopathological markers in oral cavity squamous cell carcinoma (OCSCC) patients was not studied extensively. The aim of the present study was to evaluate the prognostic value of TSR from histopathological parameters like tumour size, grade, worst pattern of invasion (WPOI), lymphovascular invasion (LVI), perineural invasion (PNI), peritumoural lymphocytic infiltrates (PLI), and lymph node metastasis (LNM) of OCSCC patients.MethodsProspective data of patients presented with OCSCC from January 2014 to May 2022 were collected and analysed. TSR was correlated with histopathological data. Resultant data was analysed using Statistical Package for the Social Sciences (IBM SPSS Statistics, Version 22.0, IBM Corp., USA).ResultsThe present study included 409 OCSCC patients with a mean age of 49.1 years (range 20–84 years). The majority were male (365, 89.2%) with history of tobacco use (276, 67.5%) and primary as buccal mucosa (263, 64.3%). Of 409 OCSCC patients, moderately (332, 81.2%) differentiated SCC was predominant followed by poor- (42, 10.3%) and well (35, 8.6%)-differentiated SCC. Of 177 (43.3%) LNM-positive patients, where 80.22% (142) are classified as having moderately differentiated SCC, while 19.77% (35) have poorly differentiated SCC. A univariate and multivariate analysis was done to assess, correlate, and investigate the role of TSR and clinicopathological parameters in predicting the LNM in patients with OCSCCs, whereas, on univariate analysis, a significant correlation (p < 0.001) between TSR and tumour size, WPOI, PNI, and PLI was observed. Whereas on multivariate analysis, a significant correlation (p < 0.05) was reported between TSR and tumour size, WPOI, PNI, and PLI.ConclusionFindings from the study indicate TSR has statistically significant association with high-risk factors of OCSCC and can be used as a useful prognostic marker in OCSCC patients. TSR analysis can be used as a simple, cost-effective, easily implemented technique in routine clinical practice, especially in developing countries.

Although Worst pattern of invasion (WPOI) is one of the histopathological (HP) markers that has been utilized in risk stratification of oral squamous cell carcinoma (OSCC) patients, its potential as an independent predictive factor for lymph node metastasis (LNM) and prognosis is least analyzed. Aim of the study is to analyze the relationship of various HP parameters to WPOI, their propensity for lymph node metastasis and prognostic value. This retrospective study included 140 patients diagnosed with resectable OSCC who underwent definitive surgery. Multiparametric HP risk assessment was done on the postoperative specimen and patients were categorized as low-risk WPOI (Type 1-3), and high-risk group (type 4 and 5). After categorization, 36.1% patients had low-risk WPOI and 63.9% had high-risk WPOI. Significant association was noted between WPOI and patient's age (p = 0.001), nodal stage (p = 0.001), lymphovascular invasion (LVI) (p = 0.006) and neural invasion (p = 0.001). 87% patients with nodal metastasis had high risk WPOI. LVI (p = 0.014) and WPOI (p < 0.001) had significant predictive role in LNM. High-risk WPOI and bone involvement were found to be predictive factors for overall survival, and only high risk WPOI had strong correlation with disease free survival having significant poor prognosis. Analyzing WPOI is essential in reporting HP specimens in OSCC. High-risk WPOI can act as an independent predictor for LNM, early recurrence and poor prognosis. Incorporation of WPOI into TNM staging is recommended to improve clinician's ability to prognosticate and individualize treatment strategies.

This study assesses the impact of adverse histologic risk factors including worst pattern of invasion (WPOI), predominant pattern of invasion (PPOI), tumor budding, and tumor infiltrating lymphocytes (TILS), on risk of recurrence in patients with early-stage Oral Cavity Squamous Cell Carcinoma (OCSCC). Retrospective chart review was performed at a single institution to identify patients with OCSCC who underwent surgical excision. Inclusion criteria included T1-T2 stage disease based on AJCC seventh edition guidelines, no cervical lymph node involvement, no perineural invasion (PNI), no lymphovascular invasion (LVI), no post-operative adjuvant radiation therapy, and cancer involving only the oral tongue or floor of mouth. Patients were excluded if they had positive final margins. A subset of 35 patients were selected for additional histologic review to determine WPOI, PPOI, TB, and TILS. Bivariable and multivariable cox analysis were performed to determine variables associated with recurrence. One hundred and sixty-one patients met criteria and were included in the analysis. Variables that were significantly associated with recurrence on bivariable analysis included tumors with high risk PPOI (groups 4 and 5; P = .021), TB with 10 or more buds (P = .021), T-stage (P = .001), neck dissection (P = .03), and depth of invasion (DOI) >4 mm (P = .044). Multivariable cox proportional hazards found T-stage (HR: 6.40; 95% CI 1.67, 24.50; P = .007), neck dissection (HR: 0.23; 95% CI 0.07, 0.82; P = .023), and TBs (HR: 1.17; 95% CI 1.05, 1.30; P = .006) to be most predictive of recurrence. TB is a strong predictor of recurrence. WPOI, PPOI, and TILS were not statistically significant risk factors for recurrence.

Nodal metastases significantly affect prognosis in oral cavity squamous cell carcinoma (OCSCC). In early-stage OCSCC (cT1-T2 cN0), management of the clinically negative neck (cN0) remains controversial. Depth of invasion (DOI) is a key determinant for END, but other histopathological parameters, such as grading, perineural invasion (PNI), lymphovascular invasion (LVI), and worst pattern of invasion (WPOI), are emerging prognostic factors. This multicenter retrospective study analyzed 1109 patients with cT1-T2 cN0 OCSCC treated at 30 Italian hospitals since 2017. Data on histopathological parameters, tumor characteristics, and patient outcomes were collected via the REDCap platform. Simple and multivariable logistic regression models were developed to assess predictors of occult nodal metastases. A total of 585 patients were clinically classified as cT1 tumors (53%), 503 as cT2 (45%), and cTis (1.9%). Of the 1109 patients, 193 (28%) had occult nodal metastases, with DOI, LVI, PNI, WPOI, and grading emerging as significant predictors. A predictive model integrating these variables demonstrated superior accuracy compared to a DOI-only model (AUROC comparison, p < 0.01). This study highlights the importance of incorporating multiple histopathological parameters into risk models for occult nodal metastases, overcoming the fixed DOI as a cutoff. The proposed predictive model offers a more precise method for guiding END in early-stage OCSCC, allowing individualized risk estimation.

Association of worst pattern of invasion in oral squamous cell carcinoma with clinicopathological parameters

Background: Oral squamous cell carcinoma (OSCC) is one of the commonest malignancies worldwide and in India. Its prognosis can be determined by various clinicopathological parameters, an important one being the worst pattern of invasion (WPOI). The present study was undertaken to assess the prognostic value of WPOI and its correlation with other prognostic parameters in determining the outcome of OSCC, correlation of these parameters with the clinical outcome, and to verify the histological risk assessment score (HRS) proposed by Brandwein-Gensler et al. in 2005. Methods and Material: In this retrospective descriptive study, 194 cases of OSCC were evaluated with at least two years of follow-up data, histopathologically for their WPOI, depth of invasion (DOI), perineural invasion (PNI), lymphovascular invasion (LVI), and lymph node metastasis with extranodal extension along with clinical outcome in the form of locoregional recurrence (LRR) and disease-specific survival (DSS). Cases were also categorized as high risk, intermediate risk, and low risk based on their WPOI and the HRS. These features were statistically correlated with WPOI and compared with the patient clinical outcome. Results: Statistically significant association was noted between WPOI and sex, histological grade, tumor and nodal stage, DOI and site of recurrence. Although no statistically significant correlation was seen between WPOI and the clinical outcomes, WPOI showed a statistically significant correlation with HRS. Also, HRS showed a significant correlation with DSS. Conclusions: WPOI, histological grade, DOI, LHR, PNI, LVI and tumor and nodal stage can be entrusted to assess the prognosis of OSCC. Of these, WPOI is the single most reliable marker for assessing the HRS-based risk status of OSCC. This study validates the HRS proposed by Brandwein-Gensler et al.

Simple SummaryOral cavity squamous cell carcinoma (OSCC) is a significant cancer burden worldwide. The current staging system for OSCC lacks accuracy in risk assessment: still, one-third of patients affected by stage I and II OSCC can develop locoregional recurrences following adequate treatment. Researchers explored the use of high-frequency intraoral ultrasonography (IOUS) to predict histological risk factors in OSCC. The results demonstrated that IOUS accurately measured the depth of invasion (DOI) and showed a strong correlation with adverse histopathological features (APFs). This promising new imaging technique could improve risk stratification for OSCC patients, potentially leading to better treatment outcomes.Despite advancements in multidisciplinary care, oncologic outcomes of oral cavity squamous cell carcinoma (OSCC) have not substantially improved: still, one-third of patients affected by stage I and II can develop locoregional recurrences. Imaging plays a pivotal role in preoperative staging of OSCC, providing depth of invasion (DOI) measurements. However, locoregional recurrences have a strong association with adverse histopathological factors not included in the staging system, and any imaging features linked to them have been lacking. In this study, the possibility to predict histological risk factors in OSCC with high-frequency intraoral ultrasonography (IOUS) was evaluated. Thirty-four patients were enrolled. The agreement between ultrasonographic and pathological DOI was evaluated, and ultrasonographic margins’ appearance was compared to the Brandwein-Gensler score and the worst pattern of invasion (WPOI). Excellent agreement between ultrasonographic and pathological DOI was found (mean difference: 0.2 mm). A significant relationship was found between ultrasonographic morphology of the front of infiltration and both Brandwein-Gensler score ≥ 3 (p < 0.0001) and WPOI ≥4 (p = 0.0001). Sensitivity, specificity, positive predictive value, and negative predictive value for the IOUS to predict a Brandwein-Gensler score ≥3 were 93.33%, 89.47%, 87.50%, and 94.44%, respectively. The present study demonstrated the promising role of IOUS in aiding risk stratification for OSCC patients.

A proportion of early-stage node-negative oral squamous carcinoma patients fail despite complete surgical resection. Adjuvant treatment in early oral cancer is controversial and is often individualized based on stage, depth, and margin status. We reviewed various histological markers in pT1/T2N0 cases, resected upfront with elective nodal dissection, with an emphasis on tumor-tissue interface characteristics of the worst pattern of invasion (WPOI), tumor cell nest size (sCNS), budding and lymphocytic host response (LHR), to assess their prognostic significance. Archived blocks of 95 cases were reviewed. Tumor stage, grade, size, depth of invasion, lymphovascular, and perineural invasion, WPOI, LHR, sCNS, and tumor bud (single cells or <5 cell clusters) score were recorded. Prognostic significance was statistically analyzed using SPSS software version 20. Depth of invasion (P = 0.008), WPOI- 4 and 5 (P = 0.033), sCNS (<5 cells) at tumor interface (P = 0.010), high bud count (≥3 buds/40 × hpf) (P = 0.021) and poor LHR (P = 0.019) correlated significantly with poor disease-free survival on univariate analysis. However, on multivariate analysis only LHR and WPOI-4 (that is presence of small cell nests or buds) were significant, with high hazard ratio of 4.351 (95% CI 1.290-14.676, P = 0.018) and 5.019 (95% CI 1.212-20.789, P = 0.026), respectively. We propose mandatory reporting of WPOI-4 at the tumor interface and absence of LHR, as significant markers of poor prognosis in early-stage oral cavity squamous carcinoma.

Aggressive histologic worst pattern of invasion (WPOI) in surrounding soft tissue has been shown to be predictive of higher local recurrence and poorer survival in oral cavity squamous cell carcinoma (OCSCC) patients. This study investigates whether aggressive WPOI can predict the mandibular invasion phenotype. Patients consecutively diagnosed with OCSCC undergoing a mandibulectomy (marginal or segmental) between 2013 and 2018 were reviewed. Senior physicians re-reviewed radiologic scans and pathologic slides of 44 cases. Aggressive WPOI (WPOI-4, 5) is significantly associated with infiltrative bone invasion. Non-aggressive WPOI (WPOI-1, 2, 3) is significantly associated with the absence of bone invasion. WPOI has become a useful tool that further characterizes the biologic behavior of OCSCC. Potentially, planned surgery may escalate from a marginal to segmental mandibulectomy based on aggressive WPOI for patients with radiographically uncertain cortical status. Further studies are needed to validate the relationship between OCSCC WPOI and mandible status.

About one-third of early stage oral cancer patients have occult nodal metastasis. High grade worst pattern of invasion (WPOI) is associated with an increased risk of nodal metastasis and poor prognosis. However, it still remains unanswered whether to perform an elective neck dissection for clinically node-negative disease or not. This study aims to evaluate the role of histological parameters including WPOI in predicting nodal metastasis in early-stage oral cancers. This analytical observational study comprised 100 patients of early-stage, node-negative, oral squamous cell carcinoma, admitted in the Surgical Oncology Department from April, 2018 till the sample size was reached. The socio-demographic data, clinical history, and findings of clinical and radiological examination were noted. The association of nodal metastasis with various histological parameters like tumour size, degree of differentiation, depth of invasion (DOI), WPOI, perineural invasion (PNI), lymphovascular invasion (LVI) and lymphocytic response was determined. SPSS 20.0 statistical tool; student's 't' test and chi-square tests were applied. While the buccal mucosa was the commonest site, the rate of occult metastasis was highest in the tongue. Nodal metastasis was not significantly associated with age, sex, smoking and primary site. While the nodal positivity was not significantly associated with tumour size, pathological stage, DOI, PNI and lymphocytic response, it was associated with LVI, degree of differentiation and WPOI. Increasing WPOI grade correlated significantly with the nodal stage, LVI and PNI, but not with DOI. WPOI is not only a significant predictor of occult nodal metastasis but can also be a novel therapeutic tool in the management of early-stage oral cancers. In patients with an aggressive WPOI pattern or other high-risk histological parameters, the neck can be addressed with either elective neck dissection or radiotherapy after wide excision of the primary tumor; otherwise, an active surveillance approach can be followed.

What additional treatment is indicated for oral cavity cancer with isolated perineural invasion?