LARYNGEAL CARCINOMA, EPIDEMIOLOGICAL
AND CLINICAL FEATURES AS SEEN AT KENYATTA
A dissertation submitted in part fulfillment of the award of degree of Masters of Medicine in ENT,
Head and Neck Surgery at the University of Nairobi
DR. FATHIYA A. ABDALLA
PROF. ISAAC M. MACHARIA
MBCHB, MMed (ENT Surgery)
Department of Surgery
University of Nairobi
I certify that this dissertation is my original work and it has not been presented for a
degree Programme in any other university.
This dissertation has been submitted for examination with my approval as a university
Signed ………………………………….. Date………………………………………….
Prof. Isaac M. Macharia
I would like to thank the following persons who assisted me accomplish my project.
1. Prof. Issac.M.Macharia; for his supervision, guidance, criticism, and support
during the entire study.
2. Dr.Nailah Kassim; for her encouragement and assistance in the preparation of
3. My colleagues for their support and input in this project.
4. Mr.Oyugi for the statistical advice.
5. Staff in the departments of ENT, Radiotherapy, Central Registry, Dental Registry,
and Histology; for their co-operation and willingness to assist.
6. Lords Healthcare for their internet searches and printing facility.
7. Harleys and GlaxoSmithKline for assisting in my presentations.
8. Last, but not least, my family who are a great pillar of support and
I dedicate this work to my husband, Mr.Hisham Mwidau, for inspiring me to
aim for higher goals in life.
Table of Contents
Table of Contents……………………………………………………5
List of Figures and Tables ………………………………………...6
Literature Review …………………………………………………..9
Justification of Study ................................................................29
Materials and Methods …………………………………………...31
Ethical Consideration …………………………………………..…36
Discussions …………………………………………………….….53 - 54
List of Figures and Tables
Figure 1: Gender ………………………………………………….37
Figure 2: Age distribution ……………………………………..….38
Figure 3: Geographical distribution ……………………………..39
Figure 4: Smoking habits ………………………………………...40
Figure 5: Alcohol Consumption ………………………………….41
Figure 6: Types of alcohol consumed ………………………….41
Figure 7: Smoking and alcohol ……………………………….…42
Figure 8: Symptoms ……………………………………………...43
Figure 9: Duration of dysphonia (months) ……………………..44
Figure 10: Comparison of DIB versus overall staging …….….45
Figure 11: Neck findings …………………………………….…...46
Figure 12: Tumour sites ………………………………………….47
Figure 13: Histopathological types ……………………………...48
Figure 14: TNM classification ……………………………………49
Figure 15: Treatment modality versus overall staging ………..50
Figure 16: Tracheostomy ………………………………………...51
Figure 17: Head and neck malignancies in the study ………...52
Table 1: Statistics of pack years of smoking …………………..40
TL Total Laryngectomy
HNSCC Head and Neck Squamous Cell Carcinoma
AJCC American Joint Committee
IUCC International Union Against Cancer
RND Radical Neck Dissection
MRND Modified Radical Neck Dissection
SND Selective Neck Dissection
DL Direct Laryngoscopy
IL Indirect Laryngoscopy
GERD Gastro-oesophageal Reflux Disease
FHG Full Hemogram
U & E’S Urea and Electrolyte
LFT’S Liver Function Tests
CXR Chest X-rays (PA view)
KNH Kenyatta National Hospital
Carcinoma of the larynx is a common head and neck malignancy. It has a widely
varying prevalence in the different regions of the world. This study, a prospective cross-
sectional survey, was designed to determine the prevalence of laryngeal carcinoma at
Kenyatta National Hospital, and the prevalence of certain risk factors such as smoking
and alcohol intake in the same patients.
62 patients with laryngeal cancer and 176 patients with other head and neck
malignancies were seen between September 2003 and December 2003.
Elderly patients between the ages of 51-70 years who smoked and/or took alcohol were
more frequently seen. The male to female ratio of affected patients was 11:1.
Most patients were from Central Province, followed by Eastern and Nairobi Provinces.
All 62 patients with laryngeal cancer had squamous cell carcinoma. The type most
encountered was the well differentiated squamous cell carcinoma.
The main presenting symptoms were dysphonia and difficulty in breathing.
Most of the patients presented with advanced disease necessitating more radical
methods of treatment. The treatment modalities given depended on the stage of
disease at presentation. All but a few patients received apt treatment.
Carcinoma of the larynx is a malignancy with a good prognosis when diagnosed and
treated early, control rates reaching 95% in certain subsites of the organ (1). Moreover it
is larglely a prevantable disease. The incidence of carcinoma of the larynx in the UK is
approximately 7.2%(2) and about 20% in the US (3) of all head and neck tumors (2). This
places upon the clinician a greater responsibility to carefully evaluate, diagnose and
treat the patients, offering a possibility of cure.
Until the late 1800s, laryngeal cancer generally was considered a fatal disease that was
palliated by tracheostomy and only rarely cured by larygo- fissure.
In 1873, Billroth performed the first total laryngectomy (TL); however this procedure
was not widely accepted for 20 years. Early experiences with laryngectomy were
associated with mortality rates as high as 94-95%.
By 1900, improved patient selection and modification of technique resulted in mortality
rate of 8.5% and long time survival rose from 4% to 44% . During the 20th century, TL
was accepted as the preferred modality for treatment of laryngeal cancer. Later, a trend
developed toward voice preservation with the development of conservation laryngeal
surgeries, radiation protocols and combined chemotherapy and radiotherapy.
Laryngeal cancer affects men more frequently than females with ratios varying in
different regions, for example a 4:1 male to female ration in the USA and 10:1 in Spain.
There has been a decrease in the ratios in recent years which is thought to be due to
increased smoking in females.
Laryngeal carcinoma is rarely seen below the age of 40 years, affecting mainly men
with a peak incidence in the seventh decade .Data from the Third National Cancer
Survey in the USA have demonstrated a slightly greater prevalence in urban centers(7).
The incidence varies worldwide. According to recent data released by the American
Cancer society, approximately 10,000 new cases of laryngeal carcinoma are diagnosed
each year in the USA and 3,900 deaths occur yearly as a result of this disease(5). Spain
has one of the highest rates in the world with an incidence approaching 20 cases per
100,000 persons in some regions. France, Poland and Italy also have high rates of the
The prevalence of laryngeal cancer in our country is not documented and no recent
data on the incidence exists. A retrospective study on carcinoma of the larynx
undertaken 17 years ago at Kenyatta National Hospital showed a total number of 109
patients only, diagnosed and treated for the same over a 10 year period (1973-83) .
Since then, there has been an increase in the number of patients managed for cancer of
the larynx (9).
ANATOMY OF THE LARYNX
The larynx, an organ of the lower respiratory system begins to develop in the 4th week
of life. Laryngotracheal groove, the respiratory primodial develops as a medial
outgrowth from the caudal end of the ventral walls of the primodial pharynx. With further
evagination forming a pouch like laryngotracheal diverticulum which finally develops into
the larynx, trachea, bronchi and the lungs.
The epithelial lining of the larynx develops from the endoderm, the cartilages from the
4th and 6th pharyngeal arch and brachial eminence. Laryngeal muscles develop from the
myoblasts in the 4th and 6th pairs of the pharyngeal arches, they are innervated by the
laryngeal branches of the vagus nervous (CNX) that supply these arches .
The larynx is a respiratory organ, set in the respiratory tract between the pharynx and
the trachea. Although phonation is important in man, the main function of the larynx is
to provide a protective sphincter at the inlet of the air passages. It also provides a
blockage to build up pressure for coughing or aiding extreme muscular efforts.
The skeletal framework of the larynx is formed of cartilages which are connected by
ligaments and membranes and are moved in relation to one another by both intrinsic
and extrinsic muscles.
The thyroid, cricoid and arytenoids cartilages are composed of hyaline cartilage and
with age parts of them ossify. The epiglottic, corniculate and cuneiform cartilages are
The larynx is divided into 3 regions and sites within each region: -
(i) Supraglottic: Comprising of laryngeal surface of the epiglottis, the arylepiglottic
folds, the laryngeal surface of arytenoids, the false cords and the ventricles.
(ii) Glottis: The 2 vocal cords, the anterior and posterior commissure.
(iii) Subglottis: Small area extending from the undersurface of the vocal cords to the
lower border of the cricoid cartilage.
The division has its basis in embryologic derivation with each side having different
lymphatic drainage. The clinical importance of this compartmentalization is that; it
provides anatomical basis for partial laryngeal surgeries; determines mode of spread
and prognosis of cancer in the three regions and in planning radiotherapy, especially for
The major cartilages of the larynx are the thyroid, cricoid, arytenoids and epiglottis. The
upper border of the thyroid cartilage is united with the hyoid bone above by the
thyrohyoid membrane. The inferior horns of the thyroid cartilages articulates below with
the cricoid cartilage by synovial joints. The thyroid cartilage encloses the larynx
anteriorly and laterally.Both true vocal cords and the false cords attach to the inside of
the thyroid cartilage anteriorly and the vocal process of each arytenoid cartilage
posteriorly. The cricoid cartilage anteriorly is united above, through its arch, with the
thyroid cartilage by the cricothyroid ligament.Below, the cricoid connects with the
trachea by the cricotracheal ligament. Articulating with upper lateral borders of the
cricoid laminae are the arytenoid cartilages.Each arytenoid resembles a 3 dimension
pyramid. The base of the pyramid is another synovial joint in which the arytenoids
cartilage can slide laterally and medially or rotate upon the cricoid cartilage. Laterally,
there is a short, blunt muscular process and anteriorly, there is a thinner vocal process,
to which the vocal cords are attached. The unpaired epiglottic cartilage, slightly curled,
leaf shaped arches diagonally upward and backward from the posterior surface of the
anterior portion of the thyroid cartilage to which it is attached by a ligament, the
thyroepiglottic ligament. The epiglottis has numerous dehiscences which facilitate
tumour spread into the pre-epiglottis space leading to the vallecula and base of tongue
The Laryngeal Musculature:
The intrinsic muscles of the larynx are all innervated by the recurrent laryngeal nerve,
except cricothyroid muscle that is supplied by superior laryngeal nerve.
1. Posterior cricoarytenoid – The only abductor of the vocal folds functions to open the
glottis. Also tenses cords during phonation.
2. Lateral cricoarytenoid – Functions to close the glottis.
3. Transverse arytenoids – The only unpaired muscle of the larynx, functions to
approximate bodies of the arytenoids closing the posterior aspect of the glottis.
4. Oblique arytenoids – Functions to close laryngeal introitus.
5. Thyroarytenoid – A very broad muscle, functions to adduct and tense the vocal fold.
6. Cricothyroid – The only one innervated by the superior laryngeal nerve. Functions to
increase tension in the vocal folds especially at higher pitch/ frequencies .
Above the vocal folds, blood supply is by the superior laryngeal artery, a branch of the
superior thyroid artery. The superior laryngeal veins accompany the artery and empty
into the superior thyroid veins. The lower half of the larynx is supplied by the inferior
thyroid artery; Venous return is by the inferior laryngeal veins to the inferior thyroid veins
The lymphatics of the larynx are separated by the vocal folds into an upper and lower
group owing to their different embryologic origin. The upper lymphatics, which are in
abundance empty into the upper deep cervical lymph nodes whereas the zone below
the vocal folds drain into the lower part of the deep cervical chain often through
prelaryngeal and pretracheal nodes.The vocal folds are firmly bound down to the
underlying vocal ligaments and this results in an absence of lymph vessels, a fact which
accounts for its low rate of metastasis to regional lymph nodes(12).
The epithelium of the larynx is mainly that of respiratory epithelium, i.e. pseudostratified
ciliated columnar epithelium. The lingual surface of the epiglottis is covered by stratified
squamous epithelium, which also covers the upper parts of laryngeal epiglottic surface
and the arylepyglottic folds.
The vocal fold, has pseudostratified squamous epithelium on the superior and inferior
surfaces with non-keratinized stratified squamous on the contact surface of the cords.
The middle layer, known as Lamina propria is composed of 3 parts. Deep to the lamina
propria is the thyroarytenoid muscle. The epithelium and the elastic portion of the
middle layer are responsible for the “mucosa wave” of vocal fold vibrations in phonation.
Mucus glands are freely distributed throughout the mucous membrane, but the vocal
folds do not posses any and gets its lubrication from the glands within the saccules (12).
There are several factors, environmental and host factors that are clearly associated
with increased incidence of laryngeal carcinoma. Tobacco (cigarette) use has been
repeatedly implicated in the genesis of laryngeal cancer. Epidemiological data have
without fail demonstrated the strong correlation between tobacco usage and laryngeal
cancer. Laryngeal cancer is extremely rare in non-smokers. Alcohol has both an
independent effect and a significant synergistic affected with tobacco in the genesis of
carcinoma of the larynx. (14, 15, 16, 17, 18)
The combination of these two increases their relative risk by 50% above that predicted
by simple additive effects Asbestos has frequently been suspected as a possible
causative agent Other occupational risk factors are exposure to mustard gas,
nickel and wood dust in wood workers. (14)
Gastrosephageal reflux disease (GERD) is seen to be an aetiologic factor in laryngeal
carcinoma .Irradiation, especially in low doses has been identified as carcinogenic to
the larynx (21).
Studies done suggest that lack of specific micro-nutrients and trace elements to be
significantly associated with laryngeal carcinoma Voice abuse and chronic laryngitis
is frequently seen in patients with laryngeal carcinoma.
Presence of recurrent respiratory papillomatosis should arouse concern regarding
possible malignant transformation Genetic susceptibility is another host risk factor
(24, 25, 26, 27).
linked with laryngeal cancer in certain individuals and ethnic groups
Over 95% of all primary laryngeal malignancies are squamous cell carcinoma, the
others being sarcoma, adenosarcoma, neuroendocrine tumors, adenoid cystic
carcinoma and others. (13, 28).
Laryngeal squamous cell result from prolonged exposure to recognized carcinogens
that cause mucosal changes. These changes from a spectrum from mucosal
hyperplesia to metaplasia, dysplasia and tissue atypia associated with or without
keratosis. These changes produce surface lesions, leucoplakia or erythroplakia known
as premalignant lesions.
These lesions are frequently seen to progress to carcinoma in situ and invasive
carcinoma. The likelihood of malignant transformation is well correlated with the degree
of cellular atypia.
A distinct variant of well-differentiated squamous cell carcinoma is the verrucous
carcinoma (Ackermans tumour) which makes up a small proportion of all laryngeal
Natural histories of the cancers in the various sites are related largely to the anatomy,
lymphatic drainage and histologic type.Actual tumour thickness and depth of inversion
certainly have an influence on metastasis and survival. (13, 28).
Early diagnosis is the key to good survival and cure rates.
1) Dysphonia; Hoarseness is a cardinal symptom of laryngeal cancer. This is due to
interference of vocal fold mucosa vibration, from tumour invasion of the mucosa
or vocalis muscle.
2) Throat discomfort or pain.
3) Neck mass;may be a direct extension to anterior neck, widening of the thyroid
cartilage or by nodal metastasis.
4) Airway obstruction; may be the presenting symptom, most commonly in
subglottic tumours. This symptom is caused by the mass effect of the tumour and
suggests that the tumour is large or in advanced stage.
5) Otalgia ; frequently a presenting symptom of supraglottic lesion
6) Haemoptysis; generally occurs only in large ulcerating tumour
7) Odynophagia; this too is frequently seen in supraglottic lesions
8) Dysphagia; it is associated with large tumours and suggests invasion beyond the
confines of the larynx
9) Weight loss; indicative of advanced local disease.
EXAMINATION OF THE PATIENT
Indirect Laryngoscopy/ Flexible Nasolaryngoscopy
General examination of the patient
Attention should be paid to:
Any signs of involvement of anterior neck
Chest X-ray(PA view): looking out for distant metastasis
CT scan: Supplements clinical determination of the extent of tumour involvement. It
is most helpful in documenting deep invasion. Tumour staging is altered in 20.2% of
those patients, with most being “up staged”
MRI: Is More expensive, but more superior in demonstrating cartilage invasion.
Ultrasound: For assessment of neck nodes
The accepted standard for definitive diagnosis is histopathologic examination of tissue
obtained at laryngoscopy and biopsy.
Urea and Electrolytes
Liver function Tests.
Provides a commonality of language that is essential for effective outcome analysis.
TNM system was developed by Pierre Denoix (1943-52).
The two widely used systems had been those of the American Joint Committee (AJCC)
and the International Union against Cancer (UICC). In 1987, the UICC and AJCC
revised their systems, thereby facilitating international data exchange. The unified
system uses the TNM staging system, which is used principally for squamous cell
OBJECTIVES OF STAGING
1. Aid the clinician in planning of treatment
2. Provide a guide to prognosis
3. Assist in evaluation of results of treatment
4. Facilitate the exchange of information between treatment centers
Surgery, irradiation, or a combination of the two serves as the mainstay of treatment of
laryngeal cancer. Vast experience has been accumulated for both methods and current
treatment protocols are largely based on empirical results. Some authors have
described neo-adjuvant chemotherapy plus irradiation for tumours that would otherwise
require total laryngectomy with good results, or concurrent chemotherapy and
Cytotoxics alone were used for palliative treatment of advanced incurable disease. The
Taxoids (eg Paclitaxel ) are the newest group of agents . Most recent reports of ongoing
research indicate that exclusive use of chemotherapy is a viable approach to treatment
of advanced laryngeal cancer. A pilot trial of TIP ( paclitaxel, ifosfamide, cisplatin ) has
showed a small percentage of patients can be rendered disease free with
chemotherapy alone (31). The study is ongoing.
Specific prognostic factors must be considered in the determination of optimal treatment
for a particular patient. These prognostic factors have a significant clinical value,
providing information that will influence the management of a given tumour e.g. giving
information as to the chance of locoregional recurrence or chance of nodal metastasis
in No necks or chance of radio-sensitivity/chemoradio sensitivity, etc.
These factors include:
(i) Host Factors
Age and General Health status. Certainly significant comorbid illness or extreme age
would argue against major surgery. Clinical pulmonary dysfunction is of specific
importance in consideration of conservation surgery. (32,33).
(ii) Tumour Factors
Tumour stage: Shown to be an independent prognostic factor for locoregion
recurrence and, or tumour specific survival. A higher stage is associated with
greater chance of nodal metastasis in laryngeal cancer. (34).
Tumour volume: can vary within a single T-stage for many sites and that
tumour volume can predict both local and the chance of metastisis(35).
Nodal Metastasis: Pathologically proven disease and detection of extra-capsular
spread are the most important prognostic factors for survival and locoregional
36, 37, 38
recurrence as shown in most series . The level of nodal metastasis carries
some prognostic importance with lower level involvement (i.e. level IV and V)
indicating poor survival 38.
Tumour Histological Grade: Histological grade of differentiation carries
independent prognostic information in terms of survival with the poorly
differentiated and anaplastic carrying the worst prognosis .
Tumour Site: Tumours from different sites differ in metastasizing potential which
in turn is related on distinct anatomic factors e.g. lymphatic drainage patterns,
proximity to cartilage. Glottic tumours do better than supraglottic or subglottic
Neoangiogenesis: There are established correlation between neoangiogenesis
and disease aggressiveness in many solid tumours. However, in head and neck
squamous cell carcinoma, the evidence is controversial 43, 44.
Immuno-histochemical and Genetic Markers: A diverse range of antigens
studied by immunohistochemistry and at genetic level can be used as prognostic
factors. The best studied are P53, Cyclin D1, epidermal growth factor receptor
and proliferation markers. Some of these e.g. P53 are molecules which are
expressed before/prior to tumour development, hence can also be used for
screening 44, 45.
(iii) Personal preferences and social circumstances of the patient and family.
(iv) Treatment facilities available, including the experience of surgeon and
Thus choice of therapy is contingent on many factors. Treatment may either be curative
or palliative for the advanced disease using the aforementioned modalities
Main considerations of cancers in this site are: -
The increased frequency of nodal metastasis (palpable/occult), a fact that argues
for treatment of the neck (Fig 3)46.
Marginal lesions carry a worse prognosis, behaving more like hypopharyngeal
High incidence of understaging with pre-epiglottic space involvement.
Small tumours of the supraglottis T 1 and T2 do well with either surgery or irradiation .
Of those irradiated, recurrences occur at the primary site or the neck while patients
treated with surgery, recurrences occur in the neck. Surgical salvage for irradiated
patients frequently requires TL.
The treatment of choice for T 3 and T4 tumours is surgery or combined treatment
because of the increased incidence of nodal involvement in these tumours. Radiation
therapy yields poor cure rates. Cervical metastatic disease may be treated by radical or
functional neck dissection plus radiotherapy. Elective neck dissection for N 0 necks has
been advocated by most authors.
Current trends are towards conservation surgery, hence achieving laryngeal
preservation with improved quality of life when compared to total laryngectomy .
Postoperative radiation is employed routinely in those patients with:
1. Bulky primary disease.
2. Histologically involved lymph nodes.
3. Resection margins not free of tumour.
Important considerations of glottic cancers are:
1. Vocal cord motion impairment, which denotes penetration of cancer into
underlying tissues from submucus membrane stiffness to frank fixation. This has
a telling effect of local control and survival rates a fact that is reflected in AJCC
2. Presence of tumour at the anterior commissure or on the arytenoids,
understaging is frequent and usually occurs because of subglottic or paraglottic
extension, often with associated cartilage invasion. Hence making radiotherapy
less effective and surgery the treament of choice.
3. Metastasis of early lesions is extremely unlikely, a fact attributed to its poor
Carcinoma in situ is a highly curable disease, but one should cautious because it is
frequently associated with areas of invasive carcinoma. Carcinoma in situ can be
treated by radiation therapy, microsurgery of the mucosa (mucosal stripping) or laser
T1 and T2 tumours have equal cure rates with either surgery (partial laryngectomy) or
1, 49, 50
radiotherapy, with cure rates over 90% . Treatment of recurrence or treatment
failure after radiotherapy is salvage surgery, the procedure of choice being total
laryngectomy . Some authors have suggested subdividing T 2 lesions into T2A – with
normal vocal cord motility and T 2B – with impaired vocal cord motility T 2B lesions
behaving more like T 3 than T2 lesions with lower cure rates than T 2A 1.
Some T3 lesions may be treated by partial laryngectomy with larger ones (T 3) requiring
near total or total laryngectomy. For some patients with advanced lesions (T 3-T4),
studies done have shown chemoradiation to be a good treatment option.
Only those patients with complete or partial response to three cycles of chemotherapy
can then be given radiotherapy plus or minus RND. Larynx preservation rate of 68% is
52, 53, 54, 55, 56, 57
possible. This is applied for patients with advanced resectable tumours .
Cervical metastasis is infrequent even in T 3 glottic carcinoma. Thus elective neck
dissection would not appear to be indicated unless transglottic invasion is suspected.
Treatment of palpable adenopathy obviously requires neck dissection plus or minus
radiotherapy. Extralaryngeal spread of tumour defines T 4 lesions. Irradiation therapy is
generally reserved for palliative treatment. Surgical treatment and appropriate
management of the neck are critical for the best results. Combined therapy is
Subglottic cancers are rare. They tend to present late as advanced lesions with cervical
metastasis and combined treatment is recommended. Surgical treatment requires total
laryngectomy plus all the soft tissues that may possibly be involved, that is the thyroid
gland and strap muscles. Post surgery irradiation include the superior mediastinum,
and should concentrate on the tracheal-stoma, since stomal recurrence is frequent in
subglottic and transglottic tumours .
ADVANCED CANCER AND PALLIATION
End stage or inoperable laryngeal disease may be amenable only to palliation. The
goals of palliative treatment are to alleviate pain, allow for adequate airway and
nutrition, and provide emotional and social support. The choice of modality
(radiotherapy, pharmacologic, surgical, chemotherapy or combination) depends
primarily on the multiple patient factors .
TREATMENT OF THE NECK
Controversy exists about the value of elective neck dissection in the face of clinically No
disease. Arguments that favour elective neck dissection are based on the finding than >
20% of No necks (supraglottis tumours) harbour histopathologic evidence of metastasis.
Hence selective neck dissection to harvest lymph nodes in regions at high risk of
metastasis is employed.
A high proportion of these do not contain tumour cells, mostly being reactive nodes.
Hence treatment will be considered prophylactic. Alternatively, one can just follow-up
patient. In supraglottic tumours, rate of metastasis to lymph node is high even for the
smallest lesions with upto 32% of negative neck done elective neck dissection turned
positive for malignancy.
For positive lymph nodes, functional neck dissection is justified. Reduced radiotherapy
is an acceptable alternative to surgery for lymph nodes <2 cm.
These require radical neck dissection because of high extranodal or extracapsular
spread of tumour. In addition to RND, radiotherapy is recommended to reduce the
incidence of recurrence. When both sides of the neck are involved, i.e N2c, bilateral
RND has a high mobidity and mortality than unilateral. In bilateral neck disease, it is
recommended doing a modified neck dissection, preserving the jugular vein and spinal
accessory nerve on the least involved side of the neck.
These fixed nodes with extra-capsular spread are in-operable and radiotherapy is
Involvement of a speech therapist is essential in maximizing recovery. Only 20-40% of
laryngectomees master oesophageal speech.
Electrovibrating devices are helpful during the immediate postoperative period and as a
Tracheo-oesophageal puncture (TEP) and placement of silicone valve-like device that is
structured to allow air into the neo-gullet but not allow food or liquids out. This
resembles the normal voice more than other methods. It can be a primary TEP,
inserted at the time of performing the TL or as a secondary procedure.
JUSTIFICATION OF THE STUDY
Laryngeal carcinoma is a common head and neck tumour. Most available data
emanates from the developed world, which might not directly reflect our local situation
due to major socio-cultural, economic and environmental differences.
This study is aimed at providing data of its epidemiology
The data generated from this study could assist in:
a) Assessing the burden of the disease.
b) Setting of public health intervention programs for primary prevention of this disease.
This being a far more cost-effective measure than treatment of established disease
whether in early or advanced stage.
c) Setting up of local patient management protocols.
d) Planning and conducting further detailed epidemiological studies of this disease in
the general population.
To determine the prevalence of Carcinoma of the Larynx in head and neck
malignancies and prevalence of certain risk factors associated with laryngeal
carcinomas in patients seen at Kenyatta National Hospital.
A. To determine the prevalence of Carcinoma of the Larynx in head and neck
B. To determine in the patients with laryngeal carcinoma, the:
1. prevalence of smoking
2. prevalence of alcohol intake
3. socio – demographic distribution
4. histopathologic types seen
5. stage at presentation
6. mode of treatment received
MATERIALS AND METHODS
This is a hospital based prospective cross-sectional study
Kenyatta National Hospital
Patients with carcinoma of the larynx, confirmed by histology who were seen and
treated both in the ENT/ Radiotherapy wards and clinics at KNH, during the study
period, and satisfied the study inclusion criteria.
Patients’ files were retrieved from the Central Records Registry, Dental
Department Registry, Radiotherapy Department, and Histology Department
Registry. This group of patients were treated in all wards and clinics at KNH with
head and neck malignancy confirmed by histology, over the same period of time.
This population was used towards calculation of the prevalence of carcinoma of
All patients with head and neck malignancies who satisfied the inclusion criteria were
recruited into the study.
The sample size for this study was estimated using the following sample size formula
for a one-sample situation 60,61
(Z1- /2)2 P (1-P)
n = _________________
n = minimum sample size
Z1- /2 = 1.96 at 95 % confidence interval
P = estimated prevalence from other studies
d = margin of precision error (10%)
The prevalence of laryngeal carcinoma in other studies was found to vary between 7%
n = 1.96 x 1.96 x 0.2 x 0.8
0.1 x 0.1
Thus the minimum sample size necessary was 62 patients.
1. All patients with head and neck malignancies with a histological diagnosis.
2. A duly signed written informed consent from the patient or guardian of patients with
carcinoma of the larynx.
Unwillingness to participate in the study (this did not jeopardize patient management).
All the files of patients with carcinoma of the larynx booked for the clinic on a particular
day was scrutinized, the files having been obtained from the medical records officer a
day before or early in the morning before starting of the clinic. Only those who actually
attended the clinic were included in the study. Daily ward rounds to check for patients
admitted with carcinoma of the larynx, confirmed by histology, were done.
Files of patients with head and neck cancers either seen or admitted in other clinics and
wards over the same period were perused. Those meeting the inclusion criterion were
The medical records were examined for pertinent historical, clinical and demographic
data. Those patients with laryngeal carcinoma who met the inclusion criteria were
explained to and invited to the study. Informed consent to participate in the study was
obtained. For each of the recruited patients with laryngeal cancer, the following was
(i) A complete medical history was obtained as per the proforma outlined in
(ii) Careful examination of the neck, looking out for any cervical lympadenopathy,
neck masses or tumour extension to the anterior neck. Those who had been
operated on, findings as per the DL operation notes were entered into the
(iii) A complete general physical examination was done.
(iv) Clinical stage of the disease as per the direct laryngoscopic findings was noted
and entered into the questionnaire.
(v) Histology of the tumour was recorded.
1. Full hemogram.
2. Urea and electrolytes.
3. Liver function tests.
A plain chest x-ray, posterior-anterior view was, to check for distant metastasis.
All data emanating from this study was entered into questionnaires, and therefrom into a
computer data base, cleaned and verified, and analysed using statistical package for
social sciences, version 10.0 and Epi6.
Prevalences were determined as percentages of the study population.
Data was analysed and presented in the form of tables, pie charts and graphs.
Any associations determined is considered statistically significant at a P value less than
or equal to 0.05.
The outcome of this study determined the prevalence and characteristics of carcinoma
of the larynx and the prevalence of its major risk factors in our local population for which
there is no recent data available.
The study will help in planning for primary and secondary intervention programs, for
laryngeal cancer in our population, this being a more cost-effective approach than
treatment of established and advanced disease for a developing nation like ours with
scarce resources. It will also help in planning of training of some of the much needed
team players in management of laryngeal cancer patients like speech therapists who
are currently scarce while the population of laryngectomees is growing bigger.
The data obtained could assist in further designing and conducting studies in this area.
The study was undertaken after approval by the Department of ENT, University of
Nairobi, and the Ethical Research Committees, KNH.
All patients recruited into the study were given a full explanation of the study and written
informed consent was sought from them.
The study did not in any way interfere with the standard management of the patients.
All information will be treated in the strictest confidence.
September 2003 to December 2003
Of the 62 patients with laryngeal cancer, 57 (91.9%) were male and 5
(8.1%) were female, giving an 11:1 male to female ratio.
Figure 2: Age distribution
30-40 41-50 51-60 61-70 >70
Laryngeal cancer occurred most frequently between the ages of 50 – 70
yrs for both sexes. The mean age was 57.8 yrs (median 58 yrs). The
youngest affected patient was 30 yrs, while the oldest was 80 yrs of age.
10 4.8 4.8
Western Rift Valley Nyanza Nairobi Eastern Coast Central
The highest population was from Central Province with 48.4%, followed by
Eastern with 14.5%, then Nairobi with 13%. This could be attributed to their
close proximity to KNH. Nyanza had the lowest with 3.2%.
Figure 4: Smoking habit
Table 1: statistics of pack years of smoking
mean median mode std. dev
21.4 19.0 40.0 17.7
Majority of patients are smokers, 47 (75.8%) patients.15 (24.2%) patients
had never smoked. This is a significant rate. 46 of the 47 smokers had >2
Figure 5: Alcohol consumption
Figure 6:Types of alcohol consumed
no. of patients
Bottled Traditional Both types Neither
47 (75.8%) had consumed alcohol, while 15 (24.2%) had not. The study
showed most patients consumed both bottled and traditional brews.
Majority of patients were either unwilling or could not recall the exact
volume of alcohol consumed over any period of time.
Smoking and Alcohol
Figure 7:Smoking and Alcohol
no. of patients
Alcohol alone Smoking alone Both alcohol and Neither
Both smoking and alcohol was seen to be more prevalent in the patients
with laryngeal carcinoma. 51 patients (82.4%) had either been smoking and
or consumed alcohol. Only 11 patients (17.7%) had taken neither.
Figure 8: Symptoms
Weight Loss 14.5
Throat pain 17.7
0 20 40 60 80 100
The most common symptom is dysphonia, seen in all of the 62 patients
(100%). Difficulty in breathing (DIB) was the second most common
symptom, seen in 45 (72.6%), with a mean duration of 7.9 weeks (median
Duration of Dysphonia
Figure 9: Duration of Dysphonia
no. of patients
5 1 0
0-6 7-12 13-18 19-24 25-30 31-36
no. of months
The duration ranged between 2 – 84 months, with a mean duration of 17.1
months (median 11 months). The mode was 12 months.
DIB versus overall staging at presentation
Figure 10: DIB versus Overall Staging at presentation
60 51.1 Yes
35.6 35.3 No
20 11.8 11.8 11.1
IV III II I
DIB was found to be statistically related to Stage IV with a relative risk of
4.34, at a 95% confidence interval of 1.15-16.47, and p value of 0.005.
Figure 11: Neck findings
loss of laryngeal
laryngeal widening 24.2
neck nodes 35.5
0 20 40 60 80 100
22 (35.5%) patients presented with lymphadenopathy, 15 (24.2%) with
laryngeal widening, 11 (17.7%) patients with loss of laryngeal creps, and
only 1 (1.6%) patient with anterior neck abscess.
Figure 12: Tumour Sites
0 20 40 60 80 100
The most common tumour site of laryngeal cancer was glottic, with 24
(38.7%) patients, followed by transglottic with 22 (35.5%), then supraglottic
with 11 (17.7%). 5 (8.1%) had tumours filling the supraglottic area,
preventing determination of inferior extent of disease on DL. No subglottic
tumours were encountered.
Figure 13: Histopathologic types
Carcinoma in situ 1.6
Poorly diff. 17.7
Moderately Well diff. 22.6
Well diff. 53.2
0 20 40 60 80 100
All 62 had squamous cell carcinoma. The most frequent type seen was the
well differentiated with 33 (53.2%) patients, followed by mod. well
differentiated with 14 (27.6%), then by the poorly diff. type with 11 (17.7%),
and anaplastic with 3 (4.8%) patients. Carcinoma in situ was the least with
only 1(1.6%) patient.
Figure 14: TNM Classification
17.7 17.7 17.7
Primary Node(N) Metastasis(M) Overall
Most of the patients with laryngeal cancer came in Stage III and IV, with a
number of 18(29.0%) and 25(40.3%) patients respectively, and a
cumulative frequency of 69.3%.
Treatment modality versus overall staging at presentation
Figure 15: Treatment versus Overall staging
12 11 11
No. of Patients
4 4 RT/Salvage TL
2 1 1 11 1 1 1
IV III II I
Most patients had optimal treatment for stage. RT was given at a dose of
60 Grays for 6 weeks, except for 1 patient who was given 66 Gy due to the
very aggressive nature of his tumour. Cytotoxics used were Cisplatin and
5FU.1 patient who was in stage IV absconded treatment.
Figure 16: Tracheostomy
The high frequency of tracheostomy is attributed to the late presentation of
Head and neck malignancies in the study
Figure 17: head and neck malignancies
in the study
salivary glands 3.4
nasal cavity and sinuses 5
oral cavity 20.6
0 5 10 15 20 25 30
Carcinoma of the larynx was the most common with a prevalence of
Globally, laryngeal carcinoma shows wide variation in disease burden 3, 4, 5. From this
study, it is determined that laryngeal cancer is the most common malignancy in head
and neck. From the total of 238 inducted into the study, 62 were those with laryngeal
carcinoma making a prevalence of 26.1%. Robin and Olofosson showed the prevalence
of laryngeal cancer in UK to be 11.1% 4.
Males are consistently affected more than females worldwide, though the ratio changes
3, 4, 5
. In Kenya, from the study the male to female ratio is 11:1. In Hagembe’s 6 (1985)
study at KNH, there was a lower ratio of 5:1.There is an increase in male
predominance, contrary to the decrease seen in the Western world 4. Could this
difference be attributed to our population being exposed to other risk factors not
considered in this study?
Patients below the age of 40 are rarely affected. The peak age range is 51-60 yrs in our
study, while that in other studies (Boyle et al, Baclays et al) 5 is 70 yrs. The youngest
patient seen was a 30 yr old female, and the oldest was an 80 yr old male.
Previous studies have conclusively proven that tobacco and alcohol are carcinogenic in
laryngeal cancer 11, 12, 13, 14, 15. It was not the aim of this study to correlate smoking and
alcohol with carcinoma of the larynx, but to show the prevalence of smoking and alcohol
use in our patients. The outcome of this study clearly shows a significant rate of 75.8%
for both smoking and alcohol consumption.
Geographically, 48% of our patients hail from the Central Province. 14% come from
Eastern and 13% from Nairobi. These are regions closest to KNH in proximity, and
probably not a true representation of the actual distribution of the disease in the country.
Nyanza had the lowest with 4%.
Clinically, all the 62 patients presented with dysphonia. The lowest duration here was 2
months. Most of these patients presented late with an average of 17 months of
dysphonia. Due to their late presentation, 72.6% also came in with difficulty in breathing.
Other symptoms seen in this study were dysphagia (22.6%), cough (17.7%), neck pains
(17.7%), otalgia (19.4%), and weight loss 14.5%.
Most common neck findings were enlarged lymph nodes at 35.5%. 24.2% had laryngeal
widening and 17.7% had loss of laryngeal crepitations. One patient alone was seen with
an anterior neck abscess.
The tumour sites in laryngeal carcinoma show variations the world over. In Hagembe 6
(1985), transglottic tumours were the most frequent. This study has glottic tumours as
the commonest (38.7%), followed by transglottic (35.5%), supraglottic (17.7%), and
undeterminable sites (8.1%).
Histopathologically, all 62 (100%) patients had squamous cell carcinoma. Most studies
cite >95% 3, 25, 26.The most encountered type was the well differentiated type seen in
53.2%, as in Hagembe’s6 with 40%.
Stage of presentation was advanced for many, with T4 tumours making up 37.1% and
overall stage of IV for 40.3%. This finding is similar to that of Hagembe’s 6 study. Their
correlation to difficulty in breathing was statistically significant with a RR=4.34, 95% CI
of 1.15-16.47, and p value of 0.005. 64.5% needed a tracheostomy. Only 2 patients
(3.2%) were seen to have distant metastases to the lungs. Majority had MX (96.8%).
Treatment modalities given were mostly dependent on the stage of disease. For most,
the treatment modalities offered were apt for their stage of presentation. Early
presentation (stages I & II) was treated with radiotherapy alone except for one who had
TL and post-operative radiotherapy, whose tumour had advanced.
Of the 43 patients with advanced disease (stages III and IV), 21 had surgery and post-
operative radiotherapy. 8 more were advised to have surgery but declined. Another 6
had inoperable disease or co-morbidity, hence radiotherapy was given with palliative
intent. The remaining 8 patients with advanced disease and with no identifiable
contraindication for surgical intervention were given radiotherapy alone. The combined
modality option was apparently not offered to them. All but one of these last 8 patients
were referrals to the KNH Radiotherapy Dept. from other hospitals. The ENT team here
had not been consulted.
1. Launch public health awareness campaigns on disease prevention
and early detection. Laryngeal cancer is largely a preventable
2. Educate primary healthcare providers in the peripheries on early
disease detection and prevention.
3. Treatment protocols should be standardized and adhered to by all
ENT, head and neck surgeons and radio-oncologists.
4. Patients diagnosed outside KNH should be discussed at the Tumour
Board for a joint assessment and optimal treatment planning.
5. Improve reporting of patients’ clinical data by the medical healthcare
providers by having a standardized proforma for inputting patients’
data and thus affording uniformity. This would subsequently provide
better patient management and relevant information for research
6. Encourage more research in laryngeal cancer with more emphasis on
other etiological factors in our environment.
7. Computerize all registries, hence making data retrieval faster and
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APPENDIX I: STUDY PROFORMA
Address: P.O.Box _________________________
IP No ______________Date_________________
Sex: Male __________ : Female __________
Previous residence( If less than 5 yrs in present residence)_____________
Did or do you take alcohol?
if yes, what kind of alcohol?
Beer Spirits Local brews
What is the duration of alcohol intake in no. of years? _________________ years.
How much alcohol was consumed in units/day?
< 7 units 7 – 21 units > 21 units
Did or do you smoke?
Used to smoke
If smoking or smoked in the past, how many sticks per day?
When did you stop smoking?
From the above, what is the number of pack years
No of cigarette sticks per day X duration in years = pack years
_____________ pack years.
Presenting symptoms and signs
1. Progressive unremitting dysphonia (hoarseness of voice)
If yes, for how long?
2. Difficulty in breathing (Dyspnoea/stridor)
If yes, for how long?
3. Was there any pain?
If yes, where was it localised? ______________
4. Weight loss?
5. Was there any neck swelling?
If yes, where was the neck swelling ?___________________________
6. Is there any cough, chest pain or abdominal pain?
7. Was there any otalgia?
8. Was there any dysphagia?
Neck Examination Findings:
1. Nodal Involvement______________________________________________________________
2. Other Findings:_________________________________________________________________
Indirect Laryngoscopy/Flexible Nasolaryngoscopy________________________________________
Normal findings Abnormal findings
If abnormal, state abnormal findings
2. U & E’s
Normal findings Abnormal findings
If abnormal, state the abnormality
Normal findings Abnormal findings
If abnormal, state the abnormal findings
If abnormal, state the pathologic findings
5. Tissue histopathology
Carcinoma in situ
(Using UICC, TNM classification system)
1. Tumour (T)
T1 T2 T3 T4
NO N1 N2 N3
3. Distant metastasis
MO MX M1
I II III IV
MODE OF MANAGEMENT
Pre- operatively Post -operatively Alone
Given alone or with neoadjuvant chemotherapy
Alone With chemotherapy
Was it for treatment of primary site, or neck or for both?
Primary site Neck Both
What was the total dose give?
_____________ Gy , over _______weeks (duration)
If yes, what type of surgery was done?
Radical neck dissection
Modified radical neck dissection
Selective neck dissection
3. Combined modalities
Surgery and radiotherapy
Chemoradiation +/- Salvage Surgery
Patient’s choice of treatment
The treatment received, was it the recommended treatment modality?
Yes _____ No _____
If the answer is No, please explain reason for
APPENDIX II: Malignancies of head and neck included in the study
Nasal cavity and sinuses
APPENDIX III: TNM STAGING
T1: Tumour Limited to one subsite, normal vocal cord mobility.
T2: Tumour Involving mucosa of more than one adjacent site of
supraglottis or glottis or adjacent region outside the supraglottis
T3: Limited to the larynx with vocal cord fixation or invades
postcricoid area, pre-epiglottic tissues or base of tongue.
T4: Extends beyond the larynx.
T1: Tumour limited to vocal cord(s).
T2: Supraglottis or sub-glottic extension, with normal/impaired
T3: Vocal Cord(s) fixation.
T4: Extends beyond the larynx.
T1: Tumour is limited to subglottis.
T2: Extends to vocal cord(s) with normal/impaired mobility.
T3: Vocal Cord fixation.
T4: Extends beyond the larynx.
REGIONAL LYMPH NODES (N)
Nx: Regional lymph node cannot be assessed
No: No regional lymph nodes.
N1: Metastasis in single ipsilateral LN 3cm or less ( <-3cm)
N2a: Metastasis in single ipsilateral LN, 3-6 cm in widest diameter.
N2b: Metastasis in multiple ipsilateral LNs, none greater than 6 cm.
N2c: Metastasis in bilateral or contralateral LN none greater than 6cm
N3: Metastasis in LN greater than 6 cm.
DISTANT METASTASIS (M)
Mx: Distant metastasis cannot be assessed.
Mo: No distant metastasis.
M1: Distant metastasis.
APPENDIX IV: Overall staging grouping for laryngeal cancer (UICC
Stage 0 Tis N0 M0
Stage I T1 N0 M0
Stage II T2 N0 M0
Stage III T1 N1 M0
T2 N1 M0
T3 N0, N1 M0
Stage IV A* T4 N0, N1 M0
IV B * Any T1,2,3 N2 M0
IV C* Any T Any N M1
* New inclusion
QUANTIFICATION OF ALCOHOL
1 Unit of alcohol is equal to -------------------------------1/2 a pint of beer
“ -------------------------------1 single measure of
distilled spirits i.e 2ml
“ --------------------------------1 glass of wine or
1 glass Sherry
This is to certify that I_______________________________the patient/
guardian to ________________________,of p.o.box______________have
consented to participate in this study of carcinoma of the larynx. I have
been informed that this study will be looking at the size of this disease in
our population and risk factors associated with it . I/patient will be required
to give a detailed and accurate history of the illness. I/patient will be
required to give blood for investigations and do a chest X-ray. I/patient is
entitled to request for results at any given time. I/patient have also been
assured that participation in the study is voluntary. Participation, refusal or
withdrawal from the study will not hamper treatment and that confidentiality
will be observed.
Patient’s Name and signature:______________________________
Guardian’s name and signature:_____________________________
Relationship to patient:____________________________________
Investigating officer: ___________________________________
Kukubali Kwa Mgojwa
Mimi, mgojwa / mlezi_______________________wa
kutoka____________________ nina kubali kujiunga na utafiti huu
wa seretani ya koo. Nime elezwa kwamba, utafiti huu ni juu ya
kima cha ugonjwa kwenye uma wetu na uraibu wa sigara na
pombe inavoonekana kwa wagojwa wa seretani ya koo. Nina /
Tuna fahamu kwamba, mgonjwa atalazimika kutowa historia kwa
ukamilifu kuhusu ugonjwa wake. Pia, ninafahamu
kwamba,mgonjwa atalazimika kutowa damu na kupigwa picha ya
kifua.Mimi kama Mgonjwa / Mlezi, nina haki ya kuitisha majibu ya
uchunguzi wakati wowote. Mimi kama Mgonjwa / Mlezi
nimehakikishiwa kwamba nina weza kukubali au kukata kujiunga
na utafiti huu , haita zuwiya kupata kwa mgojwa tiba ya kikamilifu.
Siri za mgonjwa, zitahifadhiwa.
Jina na sahihi ya Mgonjwa _______________________________
Jina na sahihi ya Mlezi __________________________________
Uhusiano Baina ya Mlezi Na Mgonjwa______________________
Jina na sahihi ya Afisa wa uchunguzi ______________________
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