Elsevier

Gynecologic Oncology

Volume 105, Issue 1, April 2007, Pages 181-188
Gynecologic Oncology

Lifetime cigarette smoke and second-hand smoke and cervical intraepithelial neoplasm—A community-based case–control study

https://doi.org/10.1016/j.ygyno.2006.11.012Get rights and content

Abstract

Background

Both active cigarette smoking and human papillomavirus (HPV) infection are known risk factors for cervical intraepithelial neoplasm (CIN). The association between second-hand smoke (SHS) and CIN has not been conclusively determined. We conducted a community-based case–control study to estimate the relationship between SHS and CIN.

Methods

Potential study subjects were selected through Pap smear screening in Kaohsiung County, Taiwan. A total of 171 subjects with either their first case of inflammation (benign epithelial lesion) or ≥ CIN1 by biopsy confirmation were assigned to a case group; 513 normal subjects with negative findings by Pap smears or biopsies were assigned to a control group.

Results

Non-smoking women exposed to more than 20 pack-years of cigarette smoke had a significantly greater risk of developing ≥ CIN2 than unexposed non-smokers (adjusted OR = 7.2, 95% CI = 2.5–20.6). Among the women without HPV infections, the greater the severity of disease found in the groups (normal, inflammation, CIN1, to ≥ CIN2), the more likely it was for the women to be exposed to SHS, a significant increasing trend (p = 0.037).

Conclusions

In addition to HPV infection and active cigarette smoking, exposure to SHS is a major risk factor for CIN among Taiwanese women.

Introduction

Cervical cancer is the second most common malignancy and the second most common cause of cancer-related death worldwide [1], [2]. In Taiwan, it is the most prevalent malignancy and the 5th leading cause of cancer deaths among women [3], [4]. Recently, the International Agency for Research on Cancer (IARC) of the World Health Organization in France completed reviewing all published studies related to cigarette smoke, second-hand smoke (SHS), and cancer [5]. While their findings showed a clear association between active cigarette smoking and cervical neoplasm, they were conflicting with regard to the relationship between SHS and the disease [5]. While Taiwanese women smoke much less than Western women (3–4% vs. ∼ 28%), a large proportion of Taiwanese men do smoke (55–62%) [6], [7], [8], [9]. This suggests that many women in Taiwan may be exposed to SHS in their homes or offices.

Although SHS is known to contain many carcinogens, studies on its association with cervical neoplasm are inconclusive [10], [11], [12], [13], [14], [15], [16], [17], [18]. Furthermore, the results of many of the studies are questionable because they did not verify exposure to SHS [12], [13], [14], [15], [16], [19] or provide information on HPV infection, a major risk factor for cervical neoplasm [20], [21], [22]. Previously, we conducted a community-based case–control study of 100 patients with cervical intraepithelial neoplasm II or over (≥ CIN2) and 197 healthy controls in Chia-Yi City, a city located on the southwestern coast of Taiwan, and found non-smoking women exposed to SHS to have a 2.73-fold greater risk (95% CI = 1.90–6.57) of developing cervical neoplasm than those who were not, after adjusting for potential confounders [19]. In this study, we conducted another community-based case–control study in Kaohsiung County, ∼ 80 km south of Chia-Yi City, to confirm our previous findings. This time, to verify exposure to SHS, we measured urinary cotinine levels, and to determine HPV infection, we measured its status of Pap smear by commercial Hybrid Capture II assay among the study women [23].

Section snippets

Study area

Kaohsiung county, located on the southwestern coast of Taiwan, has an area of ∼ 2792.7 km2 and 27 administrative districts. We did our study in 15 districts (∼ 537.6 km2), ones having an average population density more than or equal to the average population density (623 persons/km2) of Taiwan (Fig. 1).

Participants

In this community-based case–control study, whose design is described elsewhere [23], Pap smear results were provided from a community screening done by Kaohsiung County's Bureau of Health. In 15

Questionnaire

The questionnaire, which was used in a previous study, contained questions about the participant's demographic characteristics, age, educational level, cooking oil fume exposure, current and former smoking status, SHS exposure history (including dose), sexual and reproductive history, and times of prior cervical smears as well as family history of cervical cancer [19], [25].

A smoker was defined as a person smoking more than one cigarette per day for at least 1 year. Former smoker was defined as

Collection of cervical specimens

Specimens were taken from each participant's cervix by trained public health nurses using a Cytobrush (DIGENE, Gaithersburg, MD, USA) and detected by HPV DNA by Hybrid Capture II assay (DIGENE, Gaithersburg, MD, USA) for high-risk HPV, including subtype 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, and 68. The details of this analytical method are described elsewhere [23]. The technicians detecting HPV infection in this study did not know the participants' Pap smear results or cervical biopsy

Validation of smoking status

To evaluate the reproducibility of the questionnaire, we asked 100 randomly selected participants several of the same questions again 6 months later. They were interviewed by telephone by someone who did not know their previous answers to the questions. Two of the questions were about whether they were smokers and whether they were exposed to SHS. The 7 participants who reported themselves as active smokers the first time also reported themselves as active smokers the second time. Excluding

Validation of pathological reports

We randomly selected 50 (∼ 12%) cervical biopsy slides to be reconfirmed by a second pathologist (Yang SF) who was unaware of their previous pathological results. The Kappa score comparing the ≥ CIN2 (yes vs. no) in the first and second pathological reports was 0.72 (95% CI = 0.52–0.92). Using the pathological results as a gold standard from the second pathologist (Yang SF), we found that the validity of the confirmation was 88.57% (31/35) for < CIN2 and 86.67% (13/15) for ≥ CIN2. We used the

Statistical analyses

The distribution of participant characteristics was examined by χ2 or Fisher's exact test. We combined participants with pathological reports of CIN2 and over for subsequent analysis because at least 25% of high-grade squamous intraepithelial neoplasms (CIN2/CIN3) will, if not treated, progress to either CIS or invasive cervical cancer [19], [29].

Multivariate unconditional logistic regressions were then used to assess the association between different grades of CINs and different smoking and

Results

Six of the 177 potential cases (those with abnormal Pap smears) had normal biopsy findings, 54 had inflammations, 58 had CIN1, and 59 had ≥ CIN2 (20 CIN2; 34 CIN3/CIS; 5 invasive cervical cancer). The 6 participants with abnormal Pap smears but normal cervical biopsies and the 507 controls (those with normal Pap smears) were combined for subsequent analysis. There were significant differences in age distribution, education level, smoking status, times of prior Pap smears, number of lifetime

Discussion

Many epidemiologic investigations have found that, in addition to HPV infection, cigarette smoke is one of the major risk factors for cervical cancer [30], [31]. In this study, the prevalence rate of active smoking was very low (3%) among our group with normal Pap smears, and similar to the rate found in our previous study (3%) in Chia-Yi City [19] and in the normal Taiwanese women population (3–4%) [32]. The prevalence of active smoking, however, increased gradually from 3% in the normal

Acknowledgments

We gratefully acknowledge the public health nurses from Kaohsiung County for their assistance with recruiting study subjects.

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    Grant support: National Health Research Institutes, Taiwan (NHRI-EX93-9205PI), National Science Council, Taiwan (NSC 91-2320-B-037-053 and 92-2320-B-037-008), and Kaohsiung Municipal United Hospital, Kaohsiung, Taiwan.

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