Tobacco and Public Health - TCSC Indonesia

Chapter 26
Smoking and cervical neoplasia
Anne Szarewski and Jack Cuzick
Squamous cell cervical cancer is primarily related to sexual activity (reviewed by
Brinton 1992). Important risk factors are the number of sexual partners (of both the
woman and her male partner) and early age at first intercourse. Use of barrier methods
of contraception appears to be protective, whereas long-term use of the combined oral
contraceptive pill appears to increase risk (Moreno et al. 2002; Skegg 2002).
Overwhelming evidence now implicates the human papillomaviruses (HPVs), particularly
certain so-called ‘high-risk’ types (e.g. 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59,
and 68) as the causal sexually transmitted agents (Walboomers et al. 1999) although
other sexually transmitted infections such as chlamydia, herpes simplex virus (HSV),
and human immunodeficiency virus (HIV) may also have a role. The high frequency of
infection with HPV and the relative rarity of cervical cancer suggest that other factors
are needed to facilitate the carcinogenic process.
Winkelstein (1977) first drew attention to a possible role of cigarette smoking as a
cofactor. Several studies had previously reported an association but it had been dismissed
as a confounding factor for sexual variables, assumed to be either unmeasured
or recorded inaccurately. Cigarette smoking and sexual behaviour are frequently
related and the strong link between sexual behaviour and cervix cancer makes the
evaluation of any relationship with smoking very difficult. However, as demonstrated
below, the overall epidemiologic evidence supports the hypothesis that smoking is
a cofactor or risk factor in its own right, even after controlling for sexual variables.
In addition, there is now a substantial body of evidence from studies which have
controlled for the effect of HPV, and which still show a significant effect of smoking.
Three possible biological mechanisms have been proposed to explain the association,
namely a direct carcinogenic effect on the cervix of cigarette smoke metabolites, an
indirect effect mediated by an alteration of the host immune response, and an effect on
antioxidants. These will be discussed later in this chapter.
We reviewed this topic extensively in the past (Szarewski and Cuzick 1998) and in this
chapter propose to mainly update that review. Readers are therefore referred to the previous
publication for details of studies not fully covered or referenced here. An additional
feature provided here is a series of forest plots of the individual studies, which
allow simple visualization of the data. We have focused on current smoking where the
data were available, but if not, have used ever smoking as the exposure variable. No specific
attempt has been made to summarize information on dose–response and duration.