European Journal of Cardiovascular Medicine

Head and neck cancer is a prevalent disease worldwide, with its occurrence varying across different regions depending on the prevalence of associated risk factors [1]. Chronic exposure to these risk factors can lead to the development of cancer or, less commonly, field cancerization, characterized by premalignant dysplastic lesions with a high risk of progressing to cancer.

Annually, approximately 550,000 individuals worldwide are affected by head and neck cancer, with males being more commonly affected than females, with ratios ranging from 2:1 to 4:1. In certain regions such as the Indian subcontinent, France, Hong Kong, Central and Eastern Europe, Spain, Italy, Brazil, and among African American males, the annual incidence rate among males is approximately 20 per 100,000 individuals. In the United States, head and neck cancer accounts for 3% of all cancer burdens, affecting around 55,000 individuals annually, with a mortality rate of 12,000 per year. The incidence rates for cancer sites associated with HPV infections, such as the oropharynx, tonsil, and base of the tongue, are increasing among young adults in developed countries. However, the impact of HPV-induced oropharyngeal cancers on overall incidence trends is not yet fully understood [2-3].

The distribution of subsites affected by head and neck cancer varies significantly depending on risk factor exposure. Risk factors such as smoking, alcohol consumption, smokeless tobacco, and HPV infection play a uniform role worldwide. Oral cavity cancers are predominant in the Indian subcontinent, while nasopharyngeal carcinomas are common in certain regions like Hong Kong, China, Taiwan, and Malaysia. The relative contribution of these risk factors varies by subsite and geographic region. Smoking accounts for 42% of deaths from oral cavity cancers worldwide, while alcohol consumption contributes to 16% of these deaths. In India and Southeast Asian countries, smokeless tobacco products and betel quid with or without tobacco are major risk factors for oral cavity cancer [4-6].

In India, head and neck cancers collectively remain the most common type of cancer. Oral cavity cancers are predominant nationwide, followed by tongue cancers in most registries. However, in northeastern regions, pharyngeal cancers dominate followed by oral cavity cancers, although the reasons for this variation are unclear. Nasopharyngeal cancer is the rarest subsite, accounting for 0.2% to 2% of head and neck cancers. Tobacco in all forms and alcohol consumption are the primary risk factors for head and neck cancers in India, with betel nut quid also being an established risk factor for oral cavity cancers. While HPV-induced oropharyngeal cancer is well recognized in developed nations, its prevalence in India remains understudied due to cost feasibility and limited diagnostic facilities for this risk factor [7,8].

The aim of this study was to evaluate the influence of important pre-treatment variables used in the evaluation and treatment of head and neck carcinomas in predicting prognosis. Additionally, the feasibility of stratifying head and neck cancer patients into risk groups based on significant variables affecting survival endpoints was assessed.

This prospective study was conducted within a tertiary level medical institute in India. Patients visiting the outpatient department underwent evaluation for potential inclusion in the study. Inclusion criteria comprised individuals with histologically confirmed non-metastatic carcinomas impacting the oral cavity, pharynx, and larynx, characterized by squamous cell carcinoma histology. Conversely, exclusion criteria encompassed individuals with salivary gland carcinomas, nasopharyngeal carcinomas, non-squamous histology types, esophageal and OGJ tumors, metastatic disease upon presentation, and second primary cancers. Eligible patients who provided consent were subsequently enrolled in the study.

Treatment protocols encompassed primary chemoradiotherapy for pharyngeal cancers, with salvage surgery as necessary. Early oral cavity cancers underwent surgery alone or surgery followed by adjuvant chemoradiotherapy, while locally advanced disease received surgery followed by chemoradiotherapy. Alternatively, some patients underwent chemoradiotherapy with a review at 50 Gy, and subsequent management was determined based on response assessment. Chemotherapy, when administered concurrently, primarily consisted of cisplatin at a dosage of 50 mg/m2, with some patients receiving two 3-weekly courses of cisplatin 75 mg/m2 and 5-fluorouracil (5-FU) 600 mg/m2. Radiation therapy was administered using a telecobalt unit to a dose of 66 Gy in the definitive setting and as 50 Gy adjuvantly.

Statistical analysis involved the use of the Kaplan-Meier survival method for survival analysis, with the log-rank test utilized for univariate analysis of potential prognostic variables. A significance level of p ≤ 0.05, determined through a two-tailed test, was considered statistically significant. Variables demonstrating significance in univariate analysis underwent multivariate analysis using Cox's proportional regression analysis. The chi-square test and Fisher's exact test were employed as appropriate. Statistical analyses were conducted using SPSS software (version 20, IBM).

The patients' ages ranged from 21 to 83 years, with a median age of 52 years, as indicated in Table 1. The study included 181 males and 53 females, resulting in a male-to-female ratio of 3.42:1.

As shown in Table 2, oral cavity cancers were the most common, followed by hypopharynx, oropharynx, and larynx cancers. The majority of patients presented with locally advanced disease, with stage IV and stage III being predominant. Early-stage head and neck cancers (Stage I and II) accounted for approximately 27.35% of cases. Most lesions were moderately differentiated carcinomas (64.2%), with poorly differentiated tumors and well-differentiated tumors comprising 8.3% and 27.5%, respectively.

Table 3 illustrates the incorporation of various variables into a Cox's regression model, with multivariate analysis conducted. Among these variables, stage IV, grade 3, ECOG performance status, treatment-related weight loss, and treatment interruption/default exhibited significant P values, indicating their influence on survival outcomes, as shown in Table 4.

Head and neck cancers collectively constitute the most common cancers nationwide in India. Early-stage disease can be effectively managed with either surgery or radiation therapy, leading to favorable survival rates. However, locally advanced disease requires a multimodal treatment approach, which unfortunately yields suboptimal survival outcomes. The majority of patients in India present with locally advanced disease, highlighting the need for strategies to improve survival rates. Implementing early detection and treatment has been challenging in India due to various barriers. An alternative approach to enhance survival is through a risk-adapted treatment strategy, which tailors treatment to individual patients' risk levels, optimizing resource allocation to those at higher risk. Although this approach has proven effective in other cancers, it has yet to be applied to head and neck cancers [9-10].

The characteristics of the patients in this study group were typical of those attending tertiary cancer care facilities in India. Males outnumbered females and the median age at presentation was in the sixth decade. The oral cavity was the most common site of head and neck cancer, with most patients residing in urban or suburban areas and tobacco-induced cancers predominating. These findings are consistent with those of other studies. Buccal mucosa was the most frequent subsite, followed by the anterior tongue, while hypopharynx, oropharynx, and larynx were also commonly affected. The majority of patients had locally advanced disease (stage III and IV), with only 23% presenting with early-stage disease. Squamous cell histology was observed in all patients, with most tumors being moderately differentiated [11].

Various factors have been identified as predictors of survival in head and neck cancers. For instance, female sex, lower body mass index (BMI), and certain blood parameters like monocyte and platelet counts have been associated with survival outcomes [11-13]. However, in this study, age, sex, site, BMI, comorbidity, total leukocyte count, and platelet counts were not significant prognostic variables. Instead, ECOG performance status, tumor stage, grade, anemia, hypoalbuminemia, treatment-related weight loss, nutritional intervention, and treatment interruption were found to significantly affect survival. Multivariate analysis revealed that tumor stage IV, grade 3, ECOG performance status ≥ 2, treatment-related weight loss >5 kg, and treatment interruption were independently correlated with poor survival. Anemia, hypoalbuminemia, and the need for nutritional intervention were not associated with adverse survival on multivariate analysis [14-15].

Other studies have also identified various prognostic variables, including age, performance status, tumor size, site, grade, nodal status, and molecular markers like EGFR overexpression. Treatment-related weight loss has emerged as a prognostic indicator, with greater than 10% weight loss during radiotherapy associated with adverse survival outcomes and poor quality of life [16-21].

The risk stratification of head and neck cancer patients based on specific patient, tumor, and treatment-related variables is viable. Tumor stage, tumor differentiation level, ECOG performance status, treatment-associated weight loss, and treatment interruption have been identified as established prognostic factors influencing survival outcomes. By categorizing head and neck cancer patients into favorable risk, low-risk, and high-risk groups utilizing the aforementioned prognostic factors and a scoring system, distinct survival outcomes can be correlated with each risk.

1. Ferlay J, Soerjomataram I, Ervik M, Dikshit R, Eser S, Mathers C, et al. GLOBOCAN 2012: Estimated Cancer Incidence, Mortality and Prevalence Worldwide in 2012 v1.0. Lyon, France: International Agency for Research on Cancer; 2012.
2. Jemal A, Bray F, Center MM. Global cancer statistics. CA Cancer J Clin. 2011;61(2):69.
3. GLOBOCAN 2012 database. International agency for research on cancer. WHO.
4. Siegel RL, Miller KD, Jemal A. Cancer statistics 2015. CA Cancer J Clin. 2015;65(1):5.
5. Mishra A, Meherothra R. Head and neck cancer: Global burden and regional trends in India. Asian Pac J Cancer Prev. 2014;15(2):537-550.
6. Consolidated report of population-based cancer registries 2001-2004. National cancer registry programme.
7. Takiar R, Nadayil D, Nandakumar A. Projections of Number of Cancer Cases in India (2010-2020) by Cancer Groups. Asian Pacific J Cancer Prev. 2010;11:1045-104.
8. Sankaranarayanan K, Ramadas G, Thomas et al. Effect of screening on oral cancer mortality in Kerala, India: a cluster-randomised controlled trial. The Lancet. 2005;365(9475):1927-1933.
9. Badwe R, Dikshit R, Laversanne M. Cancer Incidence Trends in India. Jpn J Clin Oncol. 2014;44(5):401-7.
10. Bhattacharjee A, Chakraborty A, Purkaystha P. Prevalence of head and neck cancer in the north east-an institutional study. Indian J Otolaryngol Head Neck Surg. 2006;58(1):15-19.
11. Thakur S, Chaturvedi V, Singh AK. Pattern of ear, nose, pharynx, larynx and esophagus (ENPLO) cancers in rural based hospital. Indian J Otolaryngol Head Neck Surg. 2001;53:93-99.
12. Chen MH, Chang PM, Chen PM, et al. Prognostic significance of a pretreatment hematologic profile in patients with head and neck cancer. J Cancer Res Clin Oncol. 2009;135:1783-90.
13. Hsieh YY, Chang PM, Chen MH, et al. Pretreatment risk stratification for non-metastatic head and neck squamous cell carcinoma in a high-prevalence area. Chin Med Assoc. 2011;74(11):487-92.
14. Caro JJ, Salas M, Ward A, et al. Anemia as an independent prognostic factor for survival in patients with cancer: a systemic, quantitative review. Cancer. 2001;91:2214-21.
15. Becker A, Stadler P, Lavey RS. Severe anemia is associated with poor tumor oxygenation in head and neck squamous cell carcinomas. Int J Radiat Oncol Biol Phys. 2000;46:459-66.
16. Dasappa A, Chavan P, Arjunan R. A study of risk stratification in head and neck carcinomas in a tertiary care hospital. Eur J Mol Clin Med. 2022;9(1):488-494.
17. Baghi M, Wagenblast J, Hambek M. Pre-treatment haemoglobin level predicts response and survival after TPF induction polychemotherapy in advanced head and neck cancer patients. Clin Otolaryngol. 2008;33:245-251.
18. Rades D, Schild SE, Bahrehmand. Prognostic factors in the nonsurgical treatment of esophageal carcinoma with radiotherapy or radiochemotherapy: the importance of pretreatment hemoglobin levels. Cancer. 2005;103:1740-1746.
19. Pedersen LM, Milman N. Diagnostic significance of platelet count and other blood analyses in patients with lung cancer. Oncol Rep. 2003;10:213-216.
20. Kataria A, Nandal N, Malik R. Shahnaz Husain - A Successful Indian Woman Entrepreneur. Int J Disaster Recovery Bus Continuity. 2020;11(2):88-93.
21. Kumar S. Relevance of Buddhist Philosophy in Modern Management Theory. Psychol Educ. 2020;58(2):2104-2111.