world cancer report - iarc

Fig. 5.92 Oral leukoplakia with mild dysplasia;
leukoplakia is a precursor to oral cancer.
complex karyotypes are frequent [12] (Fig.
5.96). The genetic alterations observed in
oral cancer include activation of proto-oncogenes
such as cyclin D1, MYC, RAS, EGFR
and inactivation of tumour suppressor genes
such as those encoding p16 INK4A and p53
and other putative suppressor loci [13]. Early
changes include loss of tumour suppressor
genes on chromosomes 13p and 9p, followed
by 17p. p53 mutations and overexpression
are seen in the progression of
preinvasive lesions to invasive lesions. p53
mutations are more frequently reported in
developed (40-50%) than in developing countries
(5-25%). Tumours from India and South
East Asia are characterized by the involvement
of RAS oncogenes, including mutation,
loss of heterozygosity (HRAS) and amplification
(KRAS and NRAS). Various genetic polymorphisms
in genes such as GSTM1 or
CYP450A1 are associated with oral carcinogenesis.
Management
Surgery and radiotherapy have been the
mainstay of treatment for oral cancer. Those
with early or intermediate tumour stages are
treated with curative intent with moderate
morbidity while those with more advanced
disease are treated with definitive radiation
therapy and chemotherapy. Radical surgery
aims for tumour-free surgical margins with
the preservation of critical anatomical structures.
However, a major challenge is reconstruction
after resection to preserve function
and cosmesis. Definitive radiotherapy is
delivered either by external beams of radiation
from a telecobalt machine or linear
accelerator. The mainstay management of
lymph node metastases is by radical neck
Fig. 5.93 A moderately advanced invasive cancer
in the buccal mucosa.
dissection with or without post-operative
radiotherapy. For patients with cancer of the
larynx, very early tumours and cancer in situ
can be managed with local surgery, while
early invasive tumours can be managed with
radiation therapy. More advanced tumours
can be treated primarily with induction
chemotherapy or chemoradiotherapy, reserving
laryngectomy as a salvage procedure.
Early nasopharynx cancer is treated with
intensive radiotherapy while more advanced
cancers should be treated with a combination
of chemoradiotherapy and adjuvant
chemotherapy.
Radiotherapy may also be used to sterilize
microscopic residual cancer after surgery. In
frail patients with accessible tumours (< 3 cm
in size), brachytherapy over a 3-5 day period
may be curative. Radiotherapy to the head
and neck can lead to troublesome sideeffects.
Acute skin and mucosal inflammation
and sometimes ulcerations, as well as
superinfection with Candida (fungus), may
make normal food intake impossible and
necessitate use of a feeding tube. Later
effects may include loss of taste, reduced
and thick saliva production and a dry mouth
[14]. Dental hygiene assessment and treatment
prior to commencement of radiotherapy
are extremely important.
Chemotherapy has not been demonstrated
to elicit an overall improvement in survival,
although combinations of cytotoxic drugs
such as cisplatin, methotrexate, 5-fluorouracil
and bleomycin can cause dramatic
tumour reduction in 80-90% of cases. A
combined approach, chemoradiotherapy,
appears to improve overall survival [15].
The most important prognostic factors for
oral cancer are regional lymph node involve-
Fig. 5.94 A well-differentiated, invasive squamous
cell carcinoma of the larynx.
ment, size of the primary lesion, primary site
of cancer within the oral cavity and age. The
presence of a lymph node metastasis is the
most important negative prognostic factor in
squamous carcinoma of the mouth and pharynx.
Aggressive histopathologic features
include significant lymphovascular invasion,
perineural infiltration or high grade.
Overexpression of Bcl-2 is associated with
improved survival in head and neck cancer
patients undergoing radiation therapy, as
well as with better local control and the
absence of local lymph node involvement.
Abnormalities of 11q13 are associated with a
poor prognosis [12].
Overall population based five-year survival
from oral cancer is mostly less than 50% (Fig.
5.95) [17]. Females, in general, have a higher
Fig. 5.95 Five-year relative survival after diagnosis
of cancer of the oral cavity. USA data include both
oral and pharyngeal cancers.
Head and neck cancer
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