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 » Introduction
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ORIGINAL ARTICLE
Year : 2013  |  Volume : 50  |  Issue : 4  |  Page : 322-326
 

Synchronous primary cancers of the head and neck region and upper aero digestive tract: Defining high-risk patients


1 Department of Hospital Based Cancer Registry, Dr. B Borooah Cancer Institute, Guwahati, India
2 Department of Head and Neck Oncology, Dr. B Borooah Cancer Institute, Guwahati, India

Date of Web Publication24-Dec-2013

Correspondence Address:
M Krishnatreya
Department of Hospital Based Cancer Registry, Dr. B Borooah Cancer Institute, Guwahati
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0019-509X.123610

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 » Abstract 

Background: Patients with cancers in the head and region are at increased risk of developing synchronous primary cancers. Aim: To see the epidemiology of synchronous cancers of the head and region and identification of high-risk factors for the development of synchronous primary in the head and neck cancers. Materials and Methods: Data of head and neck cancer patients from January 2010 to December 2011 were obtained from the hospital cancer registry for retrospective analysis of patients with synchronous cancers. All synchronous malignancies were analyzed for distribution of sites, association with smoking history, stage of index head, and neck tumor and the average age of patients at presentation with synchronous cancers. The Chi-square test for association of upper aero digestive tract (UADT) and smoking and statistical formula of median for calculating the average age have been employed for analysis. Results: Incidence of synchronous primaries has been found to be 1.33%, majority were seen at the oropharynx (39.2%) and 60.7% synchronous occurred at the esophagus, 0.81% of all head and neck cancers developed synchronous primary at the esophagus. Approximately, 65% of all synchronous primaries were in Stage III and Stage IV disease and 88.2% esophageal synchronous had Stage II disease. Association of UADT synchronous cancers with smoking is highly significant, relative risk = 1.95 95% confidence interval for relative risk 1.05-3.64 P = 0.00010981 (P < 0.05) and the average age is 62.4 years in males and 57.8 years in females. Conclusion: Patients who are at the high-risk for the development of synchronous primary tumors in the cancers of the head and neck region are patients with oropharyngeal carcinoma, smoking population, patients over the age of 62 years in males, and 57 years in females and in patients with higher staged index tumor.


Keywords: High-risk patients, index tumor, synchronous tumor, upper aero digestive tract cancers


How to cite this article:
Krishnatreya M, Rahman T, Kataki A C, Das A, Das A K, Lahkar K. Synchronous primary cancers of the head and neck region and upper aero digestive tract: Defining high-risk patients. Indian J Cancer 2013;50:322-6

How to cite this URL:
Krishnatreya M, Rahman T, Kataki A C, Das A, Das A K, Lahkar K. Synchronous primary cancers of the head and neck region and upper aero digestive tract: Defining high-risk patients. Indian J Cancer [serial online] 2013 [cited 2020 May 28];50:322-6. Available from: http://www.indianjcancer.com/text.asp?2013/50/4/322/123610



 » Introduction Top


Patients with cancers in the head and region are at increased risk of developing synchronous primary cancers . The objective of this analysis is to study the epidemiology of synchronous cancers of head and region and to establish the possible high-risk factors for the development of synchronous primary in the head and neck cancers. This retrospective analysis was carried out for analyzing variables such as the occurrence, sub site distribution of index tumor, stage of the index head and neck tumor, age of the patients and association of smoking history in patients with synchronous tumor in the head and neck region. Most often the finding of a synchronous malignancy in the head and neck and upper aero digestive tract (UADT) is incidental, so the initial work up with imaging and endoscopy is helpful for the identification of a synchronous primary tumor. The criteria for classifying a tumor as a second primary malignancy have remained consistent since it was first proposed by Warren et al., [1] histological confirmation of malignancy in both the index and secondary tumors, there should be at least two cm of normal mucosa between the tumors, if the tumors are in the same location, then they should be separated in time by at least 5 years and metastatic tumor should be excluded. Synchronous second primary cancers are identified within 6 months of the index tumor. Second primary malignancies are considered "simultaneous" when the cancer is diagnosed at the same time as the index tumor or during its initial diagnostic work up. When two tumors are diagnosed simultaneously, the tumor diagnosed first is usually designated the index tumor. Survival of synchronous cancer is lower than the metachronous cancers. [2],[3]


 » Materials and Methods Top


The data of head and neck cancer patients has been obtained from the hospital based cancer registry of a Tertiary Care Cancer Hospital of Eastern India for the period of January 2010 to December 2011. A total of 4184 (N) patients with head and neck cancers with histological confirmation were included for this analysis. Carcinomas of the oral cavity, oropharynx, hypopharynx and the larynx were retrospectively analyzed to evaluate the occurrence of the synchronous primary tumors. All the head and neck cancer patients underwent routine hematologic, endoscopic procedure, radiological examination for loco regional disease, and for distant metastasis. The imaging modalities were limited to chest roentogram and computed tomography (CT) scan of the neck for the index cancer in the head and region. Positron emission tomogram (PET scan) scan was not used either in the initial work up or during the subsequent follow-up period. Bronchoscopy as an endoscopic procedure was limited to patients with the positive incidental finding on chest radiological examination. Synchronous primary had been observed along with index tumor during the initial work up and during the follow-up period upto 6 months in patients with malignancies of the oral cavity, oropharynx, hypo pharynx and larynx using endoscopy, radiology (limited to chest X-ray and CT Scan) and biopsy and/or cyto pathological examination of suspicious the lesion. All cases with synchronous malignancy were analyzed for site distribution, stage of index in relation to the occurrence of synchronous primary, association with smoking history (both present and past smokers were included), average age of the patients at presentation with synchronous cancers. Staging had been carried out according to the American Joint Committee on Cancer manual, 7 th edition (2010). The data of smoking history has been obtained by direct interview by the clinician on history taking prior to clinical examination of patients. The age of all patients were recorded at the time of registration and age was estimated by the patients The Chi-square test for association of UADT with smoking and to determine the statistical significance of the presence of synchronous in the UADT and statistical formula of median for calculating the average age have been employed for analyzing the results.


 » Results Top


Out of total 4184 patients with histological confirmation of head and neck cancer, as recorded at the hospital cancer registry, 56 (n) patients were documented with the occurrence or presence of synchronous primaries. Out of 56 patients, 47 patients were males (83.9%) and 9 (16.1%) patients were females. Forty seven (83.9%) patients were diagnosed simultaneously with the primary tumor; of which 41 (73.2%) synchronous tumor were located in the UADT and 6 (10.7%) synchronous were non upper aero digestive cancers. Nine patients (16.1%) were non simultaneous synchronous primaries. The non-simultaneous synchronous primaries were accessible to pan endoscopy on follow-up and in all nine patients with synchronous primaries were diagnosed in the UADT with upper gastro intestinal endoscopy (UGIE) as a part of esophagoscopic procedure.

Site distribution of index tumors

The distribution of site of index primary in the head and neck synchronous cancers seen in decreasing order are at the oropharynx in 22 (39.2%), oral cavity 14 (25%), hypo pharynx 12 (21.4%) and in larynx 8 (14.2%) cases.

Site distribution of synchronous tumors

The occurrence of synchronous primary site in cancers of the head and neck region, is seen in decreasing order are at the esophagus in 34 (60.7%), hypopharynx 5 (8.9%), oropharynx 5 (8.9%), larynx 3 (5.3%), oral cavity 2 (3.5%), non Hodgkin's lymphoma 2 (3.5%) and lung in 1 (1.7%) patient. Out of 34 cases of squamous carcinoma of the esophagus the frequency of distribution of synchronous primary at index head and neck sites in order of decreasing frequency are at the oropharynx in 16 (47%), hypopharynx 8 (23.5%), larynx 6 (17.6%) and in the oral cavity 4 (11.7%) cases. The occurrence of non Hodgkin's lymphoma as synchronous cancer with the primary squamous cell carcinoma in the head and neck cancer has been observed. Two patients (3.5%) of non Hodgkin's lymphoma are seen as synchronous cancer with index squamous carcinoma of the buccal mucosa and oropharynx. In our retrospective analysis, 1 (1.7%) patients with non small cell carcinoma of lung presented as a synchronous primary with head and neck squamous carcinoma at the larynx. Diagnosis of synchronous bronchogenic carcinoma was made as an incidental finding on radiological examination followed by bronchoscopy and cytopathological examination of lesion. Non small cell carcinoma of the bronchus was seen as synchronous with squamous carcinoma of the vocal cord with the duration of diagnosis as simultaneous. One patient with synchronous uterine endometrioid adeno carcinoma had index head and neck cancer at the lower alveolus (oral cavity). One patient with ductal carcinoma of the breast is seen with the index head and neck at the hypopharynx. One patient with papillary carcinoma of the thyroid had index tumor at the hypopharynx and one patient with mucoepidermoid carcinoma of parotid had index at the oropharynx.

Stage of index tumor in relation to synchronous primary cancers

In this analysis, the majority of the index tumors were staged at Stage III and Stage II at 21 (37.5%) and 17 (30.35%) respectively. Fifteen patients (26.7%) were seen at Stage IV disease and only 3 (5.3%) patients out of 56 index tumors with Stage I tumors were seen at the oral cavity, oropharynx and the larynx [Table 1]. Thirteen (61.9%) patients with Stage III disease were index primary of the oropharynx and of all esophageal synchronous primaries 30 (88.2%) patients had Stage IIA or Stage IIB disease.
Table 1: The stage distribution index tumor and stage of esophageal involvement


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Association with smoking

Smoking history was found in 46 patients, both past and present smokers are included and no history of smoking was seen in 10 patients. In cancers of UADT at both index and synchronous site, history of smoking was observed in 45 patients and no history of smoking in 5 patients [Table 2].
Table 2: Smoking history associated with UADT and Non UADT tumors


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Patients with smoking history and presence of synchronous UADT cancers were compared with smokers with non UADT cancers. In this analysis, patients with UADT cancers has a much higher prevalence of smoking (90%) as compared to the non UADT cancers (17%). This suggest that smoking habit increases the occurrence or presence of UADT synchronous cancers (relative risk = 1.95) 95% confidence interval for relative risk 1.05-3.64. Chi-square test has been used to show the statistical association of synchronous primaries related to smoking and UADT cancers. Chi-square = 14.96 on 1 d.f (degrees of freedom) compared with tabulated value of Chi-square with 1 degree of freedom at 95% confidence interval 3.84; P = 0.00010981 (P < 0.05). This shows smoking habit has been significantly associated with the occurrence of synchronous primaries in UADT. In our 2 Χ 2 Table, the total frequency is more than 40 but expected cell frequencies are lesser than five and hence we had carried out the Yates correction for a valid Chi-square test.

Average age at presentation

The age of patients presented with synchronous primaries ranges from 35 years to 91 years. The lowest age of the patient is that of male and the highest also being that of a male patient [Table 3].
Table 3: Frequency distribution by age group of patients


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The average age at presentation was analyzed with statistical formula for median



The average age of patients presenting with synchronous head and neck carcinoma is 62.4 years in males and 57.8 years in females. The average age at presentation is significantly higher in males than females.


 » Discussion Top


Multiple primaries are seen in about 9.7% of head and neck cancer patients including metachronous and synchronous malignancy of which 46.9% presents as synchronous. [4] In our series, 1.33% of all patients with head and neck cancer had synchronous primaries at different anatomical sites, both aero digestive and non aero digestive tract. Earlier reports found 1%-1.83% of head and neck cancers develop synchronous malignancy of the esophagus. [5],[6] In our series, 0.81% of all head and neck cancers developed synchronous primary at the esophagus. Patients with synchronous upper gastro intestinal cancers and head and neck cancers are predominantly male. [7] In our analysis, 84% patients were male and 26% patient's females. Head and neck squamous carcinoma is most commonly associated with the carcinoma of the esophagus as synchronous primary. [8] In this retrospective analysis, squamous carcinoma of the esophagus were present as synchronous in 60.7% of all synchronous index cancer of head and neck region. Panosetti et al., over a prolonged period of study have found that esophageal synchronous squamous carcinoma is usually associated with the hypopharyngeal cancers, [9] but in our analysis it was most commonly seen with oropharyngeal carcinoma suggesting a possible role of oncogenic human papilloma virus associated carcinogenesis concurrently or independently at both the anatomical locations. [10],[11],[12],[13],[14] This association needs evaluation with laboratory parameters for the confirmation and further viral serotyping will be needed in the context of the population at risk. Carcinoma of the lung is usually seen as a metachronous primary along with head and neck cancers; [8] however, it might also be present as synchronous primary in the bronchus. In our retrospective analysis, 1.7% patients of all synchronous malignancies of the head and neck region had associated bronchogenic carcinoma as a synchronous primary . In view of occurrence of synchronous primary of the lung with head and neck squamous carcinoma, CT scan of thorax has been advocated to screen for the lung pathology. [15] In our series, s ynchronous bronchogenic carcinoma are non small cell carcinomas and were located at segmental bronchi accessible to bronchoscopy and biopsy. Symptoms directed pan endoscopy at the initial work-up is useful for detecting synchronous primaries of the UADT, but not synchronous primaries located in the lower airways. [16] In this series, endoscopy was limited to use of direct laryngoscopy, UGIE and bronchoscopy. Available data in the literature has also highlighted the need for triple endoscopy in selected patients with head and neck cancers. [17] In our analysis, there was no role of nasopharyngoscopy and diagnostic nasal endoscopy in detecting synchronous primary in the head and neck region. In this retrospective analysis patients with an average age above 62 years in males has statistically shown to more likely yield UADT cancers in patients with head and neck carcinomas during the pre-therapeutic work up of patients; however, younger patients who develop squamous carcinoma of the head and neck are at increased risk of development of second primary cancers [18] and needs to be followed-up for a longer period with or without symptoms, with endoscopy of the UADT. Routine UGIE is not suggested in non smoking patients with oral cavity and oropharyngeal cancers as it are unlikely to identify synchronous primaries. [19] In our retrospective analysis, smoking population have been statistically shown to be a high-risk group of patients in the development of synchronous primaries in cancers of the head and neck region. Non invasive diagnostic procedures like Fluorodeoxyglucose PET/CT has also been suggested for detection of synchronous primary tumors of head and neck squamous carcinoma before doing pan endoscopy, [20] but in a limited resource setting, where PET/CT facilities are not available endoscopy remains an important tool for detection of synchronous primaries in cancers of the head and neck region. The concept of "field cancerization" in the head and neck epithelial cancer with the use of tobacco in both smoke and smokeless form can be accounted as a single most important risk factor in the development of synchronous primary in the head and neck region. [21],[22] History of smoking has been significantly associated in our analysis with UADT epithelial cancers as synchronous malignancy. Field cancerization leads to genetic variation like aberrant deoxyribonucleic acid methylation (epigenetic changes), which results in the development of second primary tumors at different anatomical region. During 5 year follow-up of head and neck cancer patients, second primary cancer free survival of 79% has been put forth. [23] The occurrence or presence of non UADT synchronous malignancies in the breast, uterine cervix, thyroid, parotid and non Hodgkin's lymphoma with head and neck squamous carcinoma suggests possible multiple etiologies and/or risk factors. Synchronous squamous cell carcinoma in the head and neck region and malignant lymphoma is rare and few have been reported. [24],[25],[26],[27] In our retrospective analysis, 0.04% patients of all malignancies in the head and neck region had synchronous malignant lymphoma. Clinical suspicion of enlarged lymph nodes of the neck is crucial in the differentiation and diagnosis of lymphoma with that of a secondary neck node, so the awareness of this association is crucial for the correct management of this small group of patients.

Synchronous primary in the head and neck cancers is commonly seen in the UADT such as the esophagus and oropharynx in the head and neck region as index tumor, which can be accessed by using endoscopic procedure like the direct laryngoscopy, and esophagoscopy as a part of UGIE procedure or esophagoscopy only. Bronchoscopy can be limited to those patients with positive findings on chest X-ray or pulmonary symptoms. Graff et al. have shown that a synchronous primary with high staged index tumor in the head and neck region and with esophageal involvement carries a poor prognosis, so identification of the presence or occurrence of synchronous primary with a low stage tumor and without esophageal involvement could most benefit from an aggressive form of treatment. [28] This can be achieved by doing UGIE to rule out the esophageal involvement. In our analysis, majority of synchronous cancers occurred with the higher staged (Stage III and Stage IV) index tumor, which is 64% of the total and in almost 65% of esophageal synchronous cancer there were associated Stage III and Stage IV index tumor. Esophageal synchronous had majority Stage II disease (88.2%).

In the absence of PET scan facilities, the detection of synchronous cancers in the head and region and UADT does not lower significantly. Triple endoscopy (direct laryngoscopy, oesophagoscopy and bronchoscopy) remains an important tool for the identification of synchronous malignancy of the UADT and as a routine procedure in the pre-therapeutic work up or as a screening procedure for the detection of synchronous primary should be used in high-risk patients.


 » Conclusion Top


In synchronous primary cancers of the head and neck region majority presents simultaneously with the index tumor. The most likely site for the occurrence of synchronous primary cancer along with index primary of the head and neck region is the esophagus. In our analysis, patients who are at the increased risk for the development of synchronous primary tumors in the cancers of the head and neck region are patients with oropharyngeal carcinoma, smoking population, patients over the age of 62 years in males and 57 years in females and in patients with higher staged index tumor.


 » Acknowledgments Top


The authors would like to thank Dr. A Nandakumar, Director in charge of National Center for Disease Informatics and Research (ICMR) for providing necessary support towards the cancer registry at our institute.

 
 » References Top

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    Tables

  [Table 1], [Table 2], [Table 3]

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