Tobacco and Public Health - TCSC Indonesia

ANNE SZAREWSKI AND JACK CUZICK 465
separately (because of small numbers). The studies which looked at adenocarcinoma
separately (Chichareon et al. 1998; Ngelangel et al. 1998) did not find a significant
association with smoking. Three studies (Chichareon et al. 1998; Ngelangel et al. 1998;
Santos et al. 2001) present results only from HPV positive cases and controls. However,
this reduces the number of women still further and, although all show an elevated OR
for smoking, none is statistically significant. IARC recognized that the individual studies
lacked power and has recently published a meta-analysis (using only HPV positive
cases and controls), which shows a significant association with smoking (OR 2.04, 95%
CI 1.32–3.14) and a dose–response effect (Plummer et al. 2003).
Lacey et al. (2001) presented results for both adenocarcinoma and squamous cancer
from a multi-centre study in the USA. Interestingly, there was a suggestion that current
smoking was inversely related with adenocarcinoma, with an odds ratio of 0.6 (95% CI
0.3–1.1), though only 18 per cent of the 124 cases and 22 per cent of the 307 controls
smoked. Numbers for the squamous cancer analysis were also small, with 91 invasive
and 48 in situ cases, of whom 43 per cent smoked. There was a positive, though nonsignificant,
association with current smoking (OR 1.6, 95% CI 0.9–2.9). HPV testing
(by consensus PCR) was not carried out on all women and some only had post-treatment
samples, which may have reduced the power of the study further.
Hildesheim et al. (2001) included both cancer and CIN in their Costa Rican study.
The analysis was restricted to HPV positive cases and controls (using both hybrid
capture II and PCR). Despite the fact that only 12 per cent of cases and 6 per cent of
controls were smokers, a significant association was found with current smoking (OR,
2.3 95% CI 1.20–4.3) and there was a dose–response relationship for those smoking
more than six cigarettes per day, having an odds ratio of 3.1 (95% CI 1.2–7.9).
Becker et al. (1994) compared Hispanic with non-Hispanic women in a university
gynaecology clinic in New Mexico. HPV status was determined by a consensus PCR.
Incident cases of CIN 2/3 were included, with the majority of both cases and controls
(64%) being of Hispanic origin. The women were relatively young, with a median age of
26 and a range of 18–40 years. An increased risk of CIN 2/3 in current smokers persisted,
even after adjustment for HPV (OR 1.8, 95% CI 1.1–3.0). Interestingly, a separate analysis
by ethnic group showed that current smoking was significant only in non-Hispanic
women, though the difference between the ethnic groups was not statistically significant.
Olsen et al. (1995) reported on women with CIN 2/3 in Norway, using PCR methods
for HPV assessment. The women were relatively young (median age 31/32 years, range
20–44 years). They found a very strong association between HPV 16 and high-grade
disease (adjusted OR 182.4, 95% CI 54.0–616.1). Information on smoking status was
limited to ever versus never smokers; the crude OR of 4.1 (95% CI 2.1–8.1) was
reduced to 1.5 (95% CI 0.5–4.3) after adjustment for HPV.
A further analysis of these data (Olsen et al. 1998) showed that HPV positive women
who smoked were at greater risk of CIN 2/3 than HPV positive women who did not
smoke (OR 2.54, 95% CI 1.13–5.72). In addition, statistical testing showed that 74 per
cent of cases were attributable to the joint effect of smoking and HPV positivity.