In cases of cervical cancer, the human papilloma virus
(HPV) has long played the role of super villain. The question
is: does HPV work alone to cause cancer? Swedish researchers
may have cracked the case. They claim to have unmasked
this super villain's sidekick. "Although HPV infection
is virtually necessary for cervical cancer, only a very
small minority of HPV-infected subjects actually develop
cancer. What makes some infections persist and eventually
develop into cancer has been an enigma," explained
Dr Joakim Dillner, professor of virology and molecular
epidemiology at Lund University, Malmö, Sweden.
Dr Dillner and other Swedish researchers
wondered if Chlamydia trachomatis, another infection
associated with cervical neoplasia, had anything to
do with it. In a clinical trial published August 10
in the International Journal of Cancer, the team
reasoned that C trachomatis-induced inflammation
might impair a woman's ability to clear HPV infections.
From May 1997, the researchers
followed 12,527 women aged 32-38 who were participating
in a study assessing primary HPV screening as a tool
for protection against high grade (II-III) cervical
intra-epithelial neoplasia (CIN) or invasive cervical
cancer. Of these, just under one-half were randomized
to immediate HPV testing, while the remainder had samples
frozen for future testing. Within the HPV-test group,
270 of 341 women who were both HPV-positive on DNA testing
and had normal Pap smears, completed a second Pap smear
and HPV DNA test at least 12 months later. Their results
were compared with those obtained from a subgroup of
337 women not initially tested for HPV, who also had
normal cytology and repeated HPV test results. Blood
samples were acquired from the women for serum C
trachomatis and Herpes simplex-2 (HSV-2) antibody
testing as well.
CHLAMYDIA
COMES CLEAN
When the numbers were crunched, the Chlamydia connection
became clearer. On that second visit, 42.6% of the women
in both groups who were HPV-positive at baseline were
persistently infected with the same type of HPV DNA.
When all other factors had been considered, the researchers
concluded that, "the most significant risk factor
for persistent presence of HPV DNA was self-reported
history of previous C trachomatis infection."
The study results also showed condom
use tended to protect against HPV persistence. "The
finding that Chlamydia is one of the determinants
of HPV persistence is of particular interest as Chlamydia
is amenable to prevention and treatment and further
emphasizes that control of chlamydial infections should
be a priority for women½s health," advised
Dr Dillner.
When preventive measures fail,
high-risk HPV (hrHPV) testing may be warranted. "The
HPV-test can better predict real danger in women with
BMD [borderline or mildly dyskeratotic] smears,"
explained Dr Theo Helmerhorst, gynecological oncologist
and Head of the Department of Obstetrics & Gynaecology
at Erasmus Medical College in Rotterdam.
In a Dutch prospective trial published
alongside the Swedish research, Dr Helmerhorst and colleagues
from four other Dutch hospitals looked at the prevalence
of hrHPV in cervical smears from 105 women with repeated
BMD cytology. The hrHPV test proved to be a powerful
tool to rule out HPV infection. "The negative predictive
value (NPV) of hrHPV testing for having high-grade CIN
was 98% at baseline for women with a repeated BMD smear,
and 100% after six and 12 months' followup," reported
the authors. "Women with a negative [hrHPV] test
do not have to worry and it is not necessary to refer
these women to the gynecologist," said Dr Helmerhorst.
Int J Cancer Aug 10, 2005
116(1):110-5,122-9
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