|Year : 2015 | Volume
| Issue : 1 | Page : 53-56
Synchronous primary cancers in the head and neck region and upper aero digestive tract: Role of triple endoscopy
M Krishnatreya1, T Rahman2, AC Kataki1, K Lahkar1
1 Department of Head and Neck Oncology, Dr. B Borooah Cancer Institute, Guwahati, Assam, India
2 Department of Head and Neck Oncology, Hospital Based Cancer Registry, Dr. B Borooah Cancer Institute, Guwahati, Assam, India
|Date of Web Publication||3-Feb-2016|
Department of Head and Neck Oncology, Dr. B Borooah Cancer Institute, Guwahati, Assam
Source of Support: National Centre for Disease Informatics and
Research (ICMR) for providing financial support towards the cancer
registry at our institute., Conflict of Interest: None
Background: Patients with cancers in the head and region are at increased risk of developing synchronous primary cancers. AIM: The aim of this study is to see the role of endoscopy in the pre-therapeutic works-up of patients with the cancers in the head and neck region. 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 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 mode for average age have been employed for analyzing results. Results: Incidence of synchronous primaries has been found to be 1.43% and mostly males were affected. The common index sites for synchronous primaries are oropharynx 22 (36.6%), oral cavity 14 (23.3%), hypopharyx 12 (20%) and larynx eight (13.3%) cases in decreasing order, 58.3% synchronous occurred at esophagus and 0.83% of all head and neck cancers developed synchronous primary at esophagus. Association of UADT synchronous cancers with smoking (odds ratio = 13.42, Chi-square 7.12 at 95% confidence interval, P = 0.0076) is highly significant and the average age is 62.6 years in males and 62 years in females. Conclusion: Endoscopy can be rationally used during the pre-therapeutic work-up of patients with a history of smoking and/or in patients over the age of 62 years. Instead of complete upper gastro intestinal endoscopy up to the second part of duodenum, only esophagoscopy is needed for the detection of synchronous primary of upper aero-digestive tract in cancers of the head and neck region.
Keywords: Bronchoscopy, index tumor, synchronous tumor, upper aero-digestive tract cancers, upper gastrointestinal endoscopy
|How to cite this article:|
Krishnatreya M, Rahman T, Kataki A C, Lahkar K. Synchronous primary cancers in the head and neck region and upper aero digestive tract: Role of triple endoscopy. Indian J Cancer 2015;52:53-6
|How to cite this URL:|
Krishnatreya M, Rahman T, Kataki A C, Lahkar K. Synchronous primary cancers in the head and neck region and upper aero digestive tract: Role of triple endoscopy. Indian J Cancer [serial online] 2015 [cited 2019 Aug 21];52:53-6. Available from: http://www.indianjcancer.com/text.asp?2015/52/1/53/175560
| » Introduction|| |
This retrospective analysis was carried out for analyzing variables like age of the patient and associated smoking history in patients with synchronous tumor in the head and neck region and to investigate the role of direct laryngoscopy, upper gastro intestinal endoscopy, and bronchoscopy as a routine procedure in the initial work-up of head and neck cancer patients. The criteria for classifying a tumor as a second primary malignancy have remained consistent since it was first proposed by Warren et al., 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.,
| » Materials and Methods|| |
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 patients with head and neck cancers with histological confirmation were included for this analysis. Carcinomas of the oral cavity, oropharynx, hypopharynx, larynx, parotid, thyroid, and cutaneous malignancy in the head and neck region were retrospectively analyzed to evaluate the occurrence of synchronous primary. All head and neck cancer patients underwent routine hematological, radiological examination and the work-up for distant metastasis whether diagnosed as an index or synchronous at the time of diagnosis. Synchronous primary had been observed along with index tumor during the initial work-up and during the follow-up period of patients with malignancies of the oral cavity, oropharynx, hypo pharynx, larynx, thyroid and skin of the head and neck region using routine endoscopy, radiology, and biopsy and/or cytopathological examination of suspicious the lesion. Bronchoscopy was limited to patients with positive findings on chest radiological examination and/or with chest symptoms.
All cases with synchronous malignancy were analyzed for site distribution, association with smoking history (both present and past smokers were included), average age of patients at presentation with synchronous cancers. 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 estimated by patients The Chi-square test for association of upper aero digestive tract (UADT) with smoking and to determine the statistical significance of the presence of synchronous in the UADT and statistical formula of mode for average age have been employed for analyzing results.
| » Results|| |
Out of total 4184 patients with histological confirmation of head and neck cancer as recorded at the hospital cancer registry, 60 (1.43%) patients were documented with the occurrence or presence of synchronous primaries. Out of 60 patients, 50 patients were males (83.3%) and ten (26.7%) patients were females. Fifty patients (83.3%) were diagnosed simultaneously with the primary tumor; of which 44 (73.3%) synchronous tumor were located in the UADT and six (10%) synchronous were non-UADT. Ten patients (17.3%) were non-simultaneous synchronous primaries. The non-simultaneous synchronous primaries were accessible to pan endoscopy on follow-up; nine cases were diagnosed in the UADT with upper gastro intestinal endoscopy and one case in the bronchial tree with bronchoscopy.
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 (36.6%), oral cavity 14 (23.3%), hypo pharynx 12 (20%), and in larynx 8 (13.3%) cases. Other head and neck sites where the primary index tumor is seen are thyroid in 2 (3.3%), parotid in 1 (1.6%), and scalp skin in 1 (1.6%). Two (3.3%) patients with papillary carcinoma of thyroid as index primary are associated with synchronous primary at the esophagus and uterine cervix. One patient (1.6%) with index of the scalp skin presented with lung synchronous tumor.
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 35 (58.3%), hypopharynx in 5 (8.3%), oropharynx in 5 (8.3%), oral cavity in 3 (5%), larynx in 3 (5%), lung in 2 (3.3%), and non-Hodgkin's lymphoma in 2 (3.3%) patients. The association of squamous carcinoma of the esophagus out of 35 cases as synchronous primary in decreasing order of frequency are at the oropharynx in 16 (45.7%), hypopharynx in 8 (22.8%), larynx in 6 (17.1%), oral cavity in 4 (11.4%), and thyroid in 1 (2.8%) patient of synchronous at the esophagus. The occurrence of non-Hodgkin's lymphoma as synchronous cancer with primary squamous cell carcinoma in the head and neck cancer has been observed. Two patients (3.3%) of non-Hodgkin's lymphoma are seen as synchronous cancer with squamous carcinoma of buccal mucosa and oropharynx. In our retrospective analysis, two (3.3%) patients with non-small cell carcinoma of lung presented as a synchronous primary with the head and neck squamous carcinoma. Diagnosis of synchronous bronchogenic carcinoma was made after symptom directed bronchoscopy and cytopathological examination of lesions. Non-small cell carcinoma of the bronchus was seen as synchronous with squamous carcinoma of the vocal cord and squamous carcinoma of the scalp skin with duration of diagnosis as simultaneous and after 4 months respectively from the date of diagnosis of the index tumor. One patient with synchronous uterine endometrioid adenocarcinoma 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.
Association with smoking
Smoking history was found in 49 patients, both past and present smokers are included and no history of smoking was seen in 11 patients. In cancers of UADT at both index and synchronous site, smoking was observed in 47 patients and no history of smoking in seven patients [Table 1].
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 (87%) as compared to the non-UADT cancers (33%). This suggest that smoking habit increases the occurrence or presence of UADT (odds ratio = 13.42). Chi-square test has been used to show the statistical association of synchronous primaries related to smoking and UADT cancers. Chi-square = 7.12 on 1 degrees of freedom (df) compared with tabulated value of Chi-square with 1 df at 95% confidence interval 3.84; P = 0.0076 (P < 0.05). This shows smoking habit has been significantly associated with the occurrence of synchronous primaries in UADT and validity of Chi-square test in this analysis. In our 2 × 2 Table, the total frequency is more than 40, but cell frequencies are less than five, so we have to do Yates correction and therefore Chi-square =
Average age at presentation
The age of patients presented with synchronous primaries ranges from 35 years to 91 years. The lowest age of patient is that of male and highest also being that of a male patient [Table 2].
The average age at presentation was analyzed with statistical formula for mode = In our retrospective analysis, the average age at presentation of synchronous primaries was observed in patients over 62 years of age. The average age of patients presenting with synchronous head and neck carcinoma is 62.6 years in males and 62 years in females. The age at presentation is slightly higher in males than females.
| » Discussion|| |
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. In our series, 1.43% 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., In our series, 0.83% 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. In our analysis, 83.3% patients were male and 26.7% patient's females. Head and neck squamous carcinoma is most commonly associated with the carcinoma esophagus as synchronous primary. In this retrospective analysis, squamous carcinoma of esophagus were present as synchronous in 58.3% of all synchronous cancer of head and neck region. Esophageal synchronous squamous carcinoma is usually associated with hypopharyngeal cancers. However, 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.,,,, This association needs further evaluation with laboratory parameters for further confirmation with laboratory parameters and viral serotyping in our population context. Carcinoma of the lung is usually seen as a metachronous primary along with head and neck cancers. However, it might also present as synchronous primary in the bronchus. In our retrospective analysis, 3.3% patients of all synchronous malignancies of the head and neck region had associated bronchogenic carcinoma as synchronous primary. Synchronous bronchogenic carcinoma and squamous carcinoma of the skin can be attributed to smoking, but a recent population based-study has shown that, smoking does not significantly increases the risk for cutaneous squamous carcinoma. This might suggest independent risk factors in the occurrence of malignancy at both these sites. In view of occurrence of synchronous primary of the lung with head and neck squamous carcinoma, computed tomogram (CT) scan of thorax has been advocated to screen for lung pathology. In our series, synchronous bronchogenic carcinoma are non-small cell carcinomas and are 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. In this series, endoscopy was limited to use of direct laryngoscopy, upper gastro intestinal endoscopy, and bronchoscopy. Available data in the literature has also highlighted the need for triple endoscopy in selected patients with head and neck cancers. 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 average age above 62 years 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  and needs to be followed-up for a longer period with or without symptoms, with endoscopy of the UADT. Routine upper gastro intestinal endoscopy is not suggested in non-smoking patients with oral cavity and oropharyngeal cancers as it are unlikely to identify synchronous primaries  and our retrospective analysis corroborates this study. Non-invasive diagnostic procedures like fluorodeoxyglucose positron emission tomography (PET)/CT has also been suggested for detection of synchronous primary tumors of head and neck squamous carcinoma before doing pan endoscopy, but in a limited resource setting, where PET/CT facilities are not available endoscopy remains an essential tool for the 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 significant risk factor in the development of synchronous primary in the head and neck region., 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 DNA 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. The occurrence or presence of non-UADT synchronous malignancies in the breast, uterine cervix, thyroid, 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.,,, 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 and secondary neck node, so the awareness of this association is crucial for the correct management of this small group of patients.
A synchronous primary in the head and neck region 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. This can be achieved by doing upper gastro intestinal endoscopy as a part of esophagoscopy procedure to rule out the esophageal involvement. In our analysis, the use of upper gastro intestinal endoscopy is limited to finding of synchronous primary in the esophagus and not distal to it like the stomach or duodenum.
Synchronous primary in the head and neck cancers is commonly seen in the UADT, which can be accessed by using endoscopic procedure such as direct laryngoscopy, upper gastro intestinal endoscopy, and bronchoscopy in selected cases. These are invasive modalities of investigation, but remain the investigation of choice as a routine procedure during the pre-therapeutic work-up of patients with squamous carcinoma of the head and neck region for the diagnosis of synchronous primary of UADT. Endoscopy as a screening procedure for the detection of synchronous primary tumors during the pre-therapeutic work-up of patients with head and neck cancer can be used in those patients who have either a history of smoking and/or in patients over the age of 62 years. Symptom directed endoscopy in the form of direct laryngoscopy, esophagoscopy, and bronchoscopy is however indicated in the initial work-up and subsequent follow-up of patients with cancers of the head and neck region. Instead of complete upper gastro intestinal endoscopy up to the second part of duodenum, only esophagoscopy is needed for the detection of synchronous primary of upper aero digestive tract in cancers of the head and neck region.
| » Acknowledgment|| |
The authors would like to thank Dr. A Nandakumar, Director in charge of National Centre for Disease Informatics and Research for providing financial support toward the cancer Registry at our institute.
| » References|| |
Warren S, Gates O. Multiple primary malignant tumors: A survey of the literature and a statistical study. Am J Cancer 1932;16:1358-414.
Di Martino E, Sellhaus B, Hausmann R, Minkenberg R, Lohmann M, Esthofen MW. Survival in second primary malignancies of patients with head and neck cancer. J Laryngol Otol 2002;116:831-8.
León X, Quer M, Diez S, Orús C, López-Pousa A, Burgués J. Second neoplasm in patients with head and neck cancer. Head Neck 1999;21:204-10.
Shikhani AH, Matanoski GM, Jones MM, Kashima HK, Johns ME. Multiple primary malignancies in head and neck cancer. Arch Otolaryngol Head Neck Surg 1986;112:1172-9.
Thompson WM, Oddson TA, Kelvin F, Daffner R, Postlethwait RW, Rice RP. Synchronous and metachronous squamous cell carcinomas of the head, neck and esophagus. Gastrointest Radiol 1978;3:123-7.
Poppendieck J. (Incidence of multiple tumors in the upper aerodigestive tract. Routine panendoscopy?). HNO 1987;35:19-23.
Bai Y, Zou DW, Li ZS. Clinical presentation, endoscopic features, treatment and prognosis of synchronous upper gastrointestinal malignancies. J Dig Dis 2012;13:19-23.
Panosetti E, Luboinski B, Mamelle G, Richard JM. Multiple synchronous and metachronous cancers of the upper aerodigestive tract: A nine-year study. Laryngoscope 1989;99:1267-73.
Tei K, Shinomiya T, Shimada T, Kimura T, Kayano K, Nakai S, et al
. Value of upper gastrointestinal endoscopic examination of head and neck cancer patients. Nihon Jibiinkoka Gakkai Kaiho 2000;103:754-60.
Guo F, Liu Y, Wang X, He Z, Weiss NS, Madeleine MM, et al
. Human papillomavirus infection and esophageal squamous cell carcinoma: A case-control study. Cancer Epidemiol Biomarkers Prev 2012;21:780-5.
Forte T, Niu J, Lockwood GA, Bryant HE. Incidence trends in head and neck cancers and human papillomavirus (HPV)-associated oropharyngeal cancer in Canada, 1992-2009. Cancer Causes Control 2012;23:1343-8.
Chaturvedi AK. Epidemiology and clinical aspects of HPV in head and neck cancers. Head Neck Pathol 2012;6 Suppl 1:S16-24.
Gupta N, Barwad A, Rajwanshi A, Kochhar R. Prevalence of human papilloma virus in esophageal carcinomas: A polymerase chain reaction-based study. Acta Cytol 2012;56:80-4.
Wittekindt C, Wagner S, Mayer CS, Klußmann JP. Basics of tumor development and importance of human papilloma virus (HPV) for head and neck cancer. Laryngorhinootologie 2012;91 Suppl 1:S1-26.
McBride P, Olsen CM, Green AC. Tobacco smoking and cutaneous squamous cell carcinoma: A 16-year longitudinal population-based study. Cancer Epidemiol Biomarkers Prev 2011;20:1778-83.
Ghosh SK, Roland NJ, Kumar A, Tandon S, Lancaster JL, Jackson SR, et al
. Detection of synchronous lung tumors in patients presenting with squamous cell carcinoma of the head and neck. Head Neck 2009;31:1563-70.
Rennemo E, Zätterström U, Boysen M. Synchronous second primary tumors in 2,016 head and neck cancer patients: Role of symptom-directed panendoscopy. Laryngoscope 2011;121:304-9.
Guardiola E, Chaigneau L, Villanueva C, Pivot X. Is there still a role for triple endoscopy as part of staging for head and neck cancer? Curr Opin Otolaryngol Head Neck Surg 2006;14:85-8.
Schwager K, Nebel A, Baier G, Hoppe F. Second primary carcinomas in the upper aerodigestive tract in different locations and age groups. Laryngorhinootologie 2000;79:599-603.
Rodriguez-Bruno K, Ali MJ, Wang SJ. Role of panendoscopy to identify synchronous second primary malignancies in patients with oral cavity and oropharyngeal squamous cell carcinoma. Head Neck 2011;33:949-53.
Strobel K, Haerle SK, Stoeckli SJ, Schrank M, Soyka JD, Veit-Haibach P, et al
. Head and neck squamous cell carcinoma (HNSCC) – Detection of synchronous primaries with (18) F-FDG-PET/CT. Eur J Nucl Med Mol Imaging 2009;36:919-27.
Basu R, Mandal S, Ghosh A, Poddar TK. Role of tobacco in the development of head and neck squamous cell carcinoma in an Eastern Indian population. Asian Pac J Cancer Prev 2008;9:381-6.
Németh Z, Czigner J, Iván L, Ujpál M, Barabás J, Szabó G. Quadruple cancer, including triple cancers in the head and neck region. Neoplasma 2002;49:412-4.
Azad AK, Bairati I, Samson E, Cheng D, Cheng L, Mirshams M, et al
. Genetic sequence variants and the development of secondary primary cancers in patients with head and neck cancers. Cancer 2012;118:1554-65.
Koletsa T, Petrakis G, Karayannopoulou G, Pappas D, Markou K, Karkavelas G, et al
. Synchronous Presence of Nasopharyngeal Carcinoma and Marginal Zone (MALT-Type) B-Cell Lymphoma in the Pharynx. Patholog Res Int 2011;2011:340763. Available from: http://www.hindawi.com/journals/pri/2011/340763/cta
. [Last accessed on 2012 Jan 7].
Yamazaki H, Nakatogawa N, Ota Y, Karakida K, Otsuru M, Kaneko A, et al
. Development of follicular lymphoma of the cervical lymph nodes in a postoperative patient with tongue cancer. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2012;113:35-9.
Albers AE, Hummel M, Keilholz U, Tzamalis G. Simultaneous squamous cell carcinoma and follicular lymphoma of the tonsil. HNO 2010;58:1192-6.
Minca EC, Popat SR, Chadha MK, Merzianu M. Small lymphocytic lymphoma obscuring microscopic tonsillar squamous cell carcinoma: An unknown occurrence with a known primary. Head Neck Pathol 2012;6:125-9.
Graff P, Schipman B, Desandes E, Mecellem H, Toussaint B, Cortese S, et al
. Management of patients with head and neck tumours presenting at diagnosis with a synchronous second cancer at another anatomic site. Clin Oncol (R Coll Radiol) 2011;23:174-81.
[Table 1], [Table 2]