Devita, Hellman, and Rosenberg's Cancer

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Chapter 3•Etiology of Cancer Part 1 51

acute liver injury, but 95% of such infections resolve with clearance of
the virus. However, 5% of patients develop persistent hepatic infection,
and these individuals are at risk of developing HCC. Patients with the
highest levels of HBV viremia display the highest HCC risk. Patients with
persistent infection can develop chronic active hepatitis and cirrhosis.
These events, through hepatocyte injury, regeneration, and inflammation,
lead to increased cellular turnover and increased risk of replicative errors
that could then lead to a transforming effect. A more direct oncogenic
effect of HBV is suggested by the presence of integrated HBV genomes
in most hepatoma cells. However, the abundance of data suggests that a
direct oncogenic effect by HBV may be relevant in only a few cases.

Answer 3.32. The answer is D.
Among the different human cancers, HPV has the greatest association
with cervical cancer. HPV-16 and HPV-18 are associated with 70% of all
cervical cancers, with other HPV strains associated with the remaining
30%. HPV is associated with penile cancers. HPV has also been linked to
some head and neck cancers, and most of the HPV-associated head and
neck cancers occur in the oral pharynx. Esophageal cancers in humans
have not been convincingly shown to be associated with HPV.

Answer 3.33. The answer is B.
Molecular studies of cervical cancer reveal that the HPV DNA is usually
integrated into the cellular genome. Integration of viral DNA is generally
not at specific sites. In HPV-positive cancers, there appears to be a selection
for the integration of E6 and E7 coding regions and the upstream regu-
latory regions. This leads to E6 and E7 genes being regularly expressed
in these cancers. The E6 and E7 proteins are oncoproteins and lead to
cellular transformation at least partly by binding the cell-cycle regulatory
proteins p53 and Rb. Only a small fraction of those individuals infected
with HPV will develop cancer, and the time interval between infection
and development of cervical cancer can be decades. It appears that HPV
infection, though essential, is not sufficient to lead to cervical cancer, and
other factors are essential for progression to invasive cancer. Epidemi-
ologic studies suggest that smoking may be such a factor because it is
associated with an increased risk of cervical cancer.

Answer 3.34. The answer is C.
HPV types 16 and 18 are the two most frequent HPV types associated with
cervical cancer and have been demonstrated in approximately 70% of
the cervical cancers. Among the other HPV types associated with cervical
cancer are HPV-31, HPV-33, HPV-39, and HPV-42, respectively. HPV-6
and HPV-11 are rarely associated with genital tract cancers.

Answer 3.35. The answer is A.
Recently approved vaccine for HPV consists of VLPs from HPV-16,
HPV-18, HPV-6, and HPV-11. The expression in yeast and insect cells
of the major HPV capsid protein L1, either alone or together with L2,
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