Human papillomavirus (HPV) infection is suspected
of causing laryngeal carcinoma. The relationship of HPV-16 and
18 genotypes to apoptosis and p53 protein expression in Egyptian
laryngeal carcinoma patients was studied. Biopsy specimens from
82 patients with laryngeal carcinoma and 28 with minimal
pathological lesions serving as a control group were examined. In
all specimens, HPV-16 and-18 were examined using PCR, p53
expression was studied by immunohistochemistry and DNA
fragmentation to assess apoptosis was assayed using a
biochemical method and gel electrophoresis. HPV-16 was
detected in 51.2% of laryngeal carcinoma patients versus 14.3%
of the control group (p=0.001). The surrounding areas of
positive tumors were negative in 524% of them. HPV-16 was
significantly higher in tumors with higher expression of p53
(p=0.026). An inverse significant relationship was found between
HPV-16 and DNA fragmentation in the laryngeal carcinoma
group (p=0.022). HPV-18 was detected in only 24% of laryngeal
carcinoma patients. p53 protein was expressed in 76.8% of the
malignant group with significant increasing positivity with
increasing stage of the disease (p =am). Non of the control
group was p53-positive. Our results suggest that highly oncogenic
types of HPV may play a role in the pathogenesis of laryngeal
carcinoma through inactivation of wild-type p53 with subsequent
decrease in apoptosis and by induction of p53 mutation, which
itself can induce malignant transformation.
Increasing evidence suggests that human papillomavirus
(HPV) infection is associated with an increased risk of
epithelial cancer (1). HPV is a small ( — 7,900 base pairs)
double-stranded circular DNA virus belonging to
papovaviruses. It is capable of infecting epithelial cells
Correspondence to: Samar K. Kassim, Medical Biochemistry
Department, Ath Shams Faculty of Medicine, Cairo, Egypt. e-mail:
samar_kassim@ems.org.eg
Key Words: HPV-16, HPV-18, apoptosis, p53, laryngeal carcinoma.
resulting in a variety of pathological lesions. Under certain
yet unknown circumstances, the viral genome may become
integrated into the cellular genome, which may lead to
malignant transformation (2). Laryngeal cancer is one of
those pathological lesions related to HPV infection (3).
Among the more than 100 different types of HPV
identified, type 16 is the most common high-risk genotype
(4). Type 18 is another high-risk genotype (3). The viral
genome contains coding regions referred to as open reading
frames (ORFs). ORFs that encode nonstructural proteins
are referred to as early (E) genes and those that encode
structural proteins are termed late (L) genes, in accordance
with the time in the viral life cycle that they are expressed
(5). Integration disrupts the viral genome in the E1-E2
region, resulting in the failure of transcription of the late
genes and possibly in uncontrolled transcription of the E6
and E7 genes (2). Expression of the E6 and E7 proteins of
HPV-16 and 18 is sufficient for the immortalization of
primary human epithelial cells and induces premalignant
1-WV-associated squamous intra-epithelial lesions (6). It has
been well documented that E6 and E7 oncoproteins alter
normal cell growth control mechanisms by inactivating two
well-characterized tumor suppressor proteins, p53 and
retinoblastoma protein, respectively (7). p53 is a cell cycle
"checkpoint" protein, important for cell cycle regulation and
is functionally inactivated in human cancer at a high
frequency (8). The E6 protein of HPV-16 and 18 binds to
p53 and targets it for degradation through the ubiquitin
pathway (9). E6 viral protein has additional biological and
transforming activities that appear independent of p53 (10).
It has been reported to interact with a number of cellular
proteins including proteins involved in apoptosis such as
Bak (11), c-Myc (12) and tumor necrosis factor (TNE)(13).
In the present work, we studied the incidence of HPV
infection among laryngeal cancer patients in Egypt. The
relationship of the HPV genotypes 16 and 18 to apoptosis
and p53 protein expression in laryngeal tumor tissues in
comparison to benign lesions was addressed.
1109-6535/2004 $2.00+ .40 |
