Skip to main content Accessibility help
×
Home

Information:

  • Access
  • Cited by 6

Actions:

      • Send article to Kindle

        To send this article to your Kindle, first ensure no-reply@cambridge.org is added to your Approved Personal Document E-mail List under your Personal Document Settings on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part of your Kindle email address below. Find out more about sending to your Kindle. Find out more about sending to your Kindle.

        Note you can select to send to either the @free.kindle.com or @kindle.com variations. ‘@free.kindle.com’ emails are free but can only be sent to your device when it is connected to wi-fi. ‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.

        Find out more about the Kindle Personal Document Service.

        Alcohol consumption and persistent infection of high-risk human papillomavirus
        Available formats
        ×

        Send article to Dropbox

        To send this article to your Dropbox account, please select one or more formats and confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your <service> account. Find out more about sending content to Dropbox.

        Alcohol consumption and persistent infection of high-risk human papillomavirus
        Available formats
        ×

        Send article to Google Drive

        To send this article to your Google Drive account, please select one or more formats and confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your <service> account. Find out more about sending content to Google Drive.

        Alcohol consumption and persistent infection of high-risk human papillomavirus
        Available formats
        ×
Export citation

Summary

Alcohol consumption is a possible co-factor of high-risk human papillomavirus (HR-HPV) persistence, a major step in cervical carcinogenesis, but the association between alcohol and continuous HPV infection remains unclear. This prospective study identified the association between alcohol consumption and HR-HPV persistence. Overall, 9230 women who underwent screening during 2002–2011 at the National Cancer Center, Korea were analysed in multivariate logistic regression. Current drinkers [odds ratio (OR) 2·49, 95% confidence interval (CI) 1·32–4·71] and drinkers for ⩾5 years (OR 2·33, 95% CI 1·17–4·63) had a higher risk of 2-year HR-HPV persistence (HPV positivity for 3 consecutive years) than non-drinkers and drinkers for <5 years, respectively (vs. HPV negativity for 3 consecutive years). A high drinking frequency (⩾twice/week) and a high beer intake (⩾3 glasses/occasion) had higher risks of 1-year (OR 1·80, 95% CI 1·01–3·36) HPV positivity for 2 consecutive years) and 2-year HR-HPV persistence (OR 3·62, 95% CI 1·35–9·75) than non-drinkers. Of the HPV-positive subjects enrolled, drinking habit (OR 2·68, 95% CI 1·10–6·51) and high consumption of beer or soju (⩾2 glasses/occasion; OR 2·90, 95% CI 1·06–7·98) increased the risk of 2-year consecutive or alternate HR-HPV positivity (vs. consecutive HPV negativity). These findings suggest that alcohol consumption might increase the risk of cervical HR-HPV persistence in Korean women.

INTRODUCTION

Human papillomavirus (HPV) infection has been established as the primary cause in the development of cervical intraepithelial neoplasia (CIN) and cervical cancer [1]. However, HPV infections are usually transient and mostly regress to a virus-free status or low-grade lesions [2]. By contrast, persistent infection with carcinogenic HPV genotypes causes CIN lesions and cervical cancer development [2, 3]. HPV persistence has been reportedly associated with viral variants such as viral genotypes, multiple infections, and viral loads [4] as well as host genetic variability, especially in genes that control the immune response [5]. Several host epidemic characteristics including older age [2, 6], multiple sexual partners [2, 7], smoking [7], individual immune responsiveness [8], and oral contraceptive use [9] have also been reportedly associated with HPV persistence, but the results related to these epidemiological factors are highly controversial.

Alcohol is a potential risk factor of oral, oesophageal, colorectal, and liver cancers [10] and has been reported to increase the risk of breast, endometrial, and ovarian cancers by enhancing oestrogen levels and metabolism [11]. However, epidemiological evidence for cervical cancer is lacking and controversial [12]. Alcohol is known to be a potential risk factor of HPV infection (acquisition), but there are few studies on the association of alcohol consumption and HPV persistence [2, 13]. Furthermore, no studies have reported on specific alcohol consumption behaviours such as frequency, duration, and specific types of alcoholic beverages consumed, relative to HPV persistence.

The aim of our prospective study was to investigate the alcohol consumption characteristics (drinking status, frequency, duration of drinking, and the amount of alcoholic beverages consumed) in association with a high risk (HR)-HPV persistence according to the subjects' health screening data.

METHODS

Study design and population

A total of 10 444 Korean women who underwent health-screening examinations at the National Cancer Center from 2002 to 2011 and provided signed informed consent were included in this study. This health screening examinee study is part of the Korean Prospective Study for the Transition of Human Papillomavirus into Cervical Carcinoma (KOVIC). KOVIC is the prospective study established to identify host and environmental co-factors in the persistent HPV infection and its transformation into cervical carcinoma in Korean women. KOVIC is composed to two studies, a health examinee-based prospective study and a patient-based prospective study. There is an ongoing follow-up investigation. The study protocol was approved by the Institutional Review Boards and Ethics Committee of the National Cancer Center in Korea (NCCNCS-11-433). After excluding 558 women who did not participate in HR-HPV deoxyribonucleic acid (DNA) testing and 656 women who did not complete the questionnaire about detailed alcohol consumption behaviours, a total of 9230 women were available for HPV infection analysis. We collected HPV DNA data, cytology findings (Pap smear), and questionnaires about detailed alcohol consumption behaviours, sociodemographics, smoking history, parity, menopausal status, and oral contraceptive use for these 9230 women. Among them, 1284 and 543 women with a cytological result of low-grade squamous intraepithelial lesion (LSIL) or less for the study period were available for 1- and 2-year follow-up studies, respectively, after excluding six subjects. Five subjects and one subject had cytology findings of high-grade squamous intraepithelial lesion (HSIL) or worse in the 1- and 2-year follow-up, respectively.

Two definitions of HR-HPV persistence were used in this study. First, 1-year HPV persistence was defined as HR-HPV positivity in the enrolment year and the 1-year follow-up study year, and 2-year HPV persistence was defined as HR-HPV positivity in the enrolment year and both the 1- and 2-year follow-up study years. One- and 2-year HPV negatives were defined as HPV negativity in the 1-year follow-up study year and as HPV negativity in both the 1- and 2-year follow-up study years, respectively, after enrolment with HPV negativity. According to these definitions, 10·1% of the 9230 women were HPV positive (negative, 8301; positive, 929) at enrolment. In the follow-up study, 127 and 46 women were included in the 1- and 2-year HPV-persistence categories, and 949 and 373 women were included in the 1- and 2-year HPV-negative categories, respectively.

An additional analysis was performed to compare the statuses of those cleared of HR-HPV and those still infected by HR-HPV for the two follow-up years. Two-year consecutive or alternate HR-HPV persistence was defined as HPV positivity/HPV positivity, as HPV positivity/HPV negativity, or as HPV negativity/HPV positivity in both the next year and the subsequent year, respectively, after enrolment with HPV positivity. Two-year consecutive HR-HPV clearance was defined as HPV negativity in both the next year and the subsequent year after enrolment with HPV positivity. By this definition, 140 women (2-year consecutive or alternate persistence: 89, 2-year consecutive clearance: 51) were included in the second analysis.

Questionnaires related to alcohol consumption behaviours

General characteristics were analysed with the questionnaire that included age, height, weight, marital status, number of children, menopausal status, oral contraceptive use, education level, income level, and cigarette smoking status. A detailed questionnaire about alcohol consumption included drinking status (current, former, never), the frequency of alcohol consumption (once/month, 2–3 times/month, once/week, 2–3 times/week, 4–5 times/week, every day, twice/day), duration of drinking habit (<5 years, ⩾5 years), and usual consumption per drinking occasion of two alcoholic beverages, beer and soju at 200 cc and 50 cc, respectively (1 glass, 2 glasses, ⩾3 glasses). Soju is a distilled beverage native to Korea and its alcohol content is usually about 20% ethanol by volume.

HPV DNA detection and Pap smear

HR-HPV DNA detection was performed with the commercially available Hybrid capture II system (HC-II, Digene Co., USA). A chemiluminescent HPV DNA test was measured as relative light units (RLU) with a probe designed for 13 types of HR-HPV (HPV types 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 68). The test results were read as positive at concentrations of ⩾1 pg/ml of RLU/cut-off ratio (RLU of specimen/mean RLU of two positive controls). The cytological grades for Pap smear reports were based on the Bethesda classification system [14]. Types of results in this system included normal cells, atypical squamous cells, LSIL, HSIL, squamous cell carcinoma, atypical glandular cells, and adenocarcinoma in situ.

Statistical analysis

The χ 2 test and t test were used to analyse differences in the distributions of categorical and continuous general variables, respectively. Multivariate logistic regression models were used to estimate the odds ratios (ORs) and corresponding 95% confidence intervals (CIs). A regression analysis was performed to assess the association between several characteristics related to alcohol consumption and HR-HPV infection (vs. HPV negativity) and between those and 1- and 2-year HR-HPV persistence groups (vs. 1- and 2-year HR-HPV negative groups, respectively). The model was adjusted for age, body mass index (BMI), marital status, parity, menopausal status, oral contraceptive use, education level, income level, and smoking habit as categorical variables indicated in Table 1. Another multivariate logistic regression analysis was performed to estimate the risk of 2-year consecutive or alternate HR-HPV persistence (vs. HR-HPV clearance) associated with the characteristics related to alcohol consumption after adjustment for age, BMI, parity and education level as categorical variables. The risk estimates were calculated using the non-drinkers or non-alcoholic characteristics as the non-exposure category. The statistical analysis and graphical design were performed with SAS v. 9·1 (SAS Institute, USA) and Stata v. 12·0 (Stata Corp., USA) software packages.

Table 1. General characteristics of study subjects at baseline (n = 9230)

BMI, Body mass index; RLU/CO, relative light units/cut-off; ASCUS, atypical squamous cells of undetermined significance; LSIL, low-grade squamous intraepithelial lesion; HSIL, high-grade squamous intraepithelial lesion.

Data in this table indicates the number of subjects (n) and the percentage of subjects (%) among the enrolled non-drinkers and drinkers.

P values for the categorical and continuous variables were obtained from χ 2 test and t test, respectively.

RESULTS

General characteristics of the study subjects at baseline

As shown in Table 1, about 50% of the 9230 enrolled subjects were drinkers (4578). The mean ages of the non-drinkers and drinkers were 50·1 and 45·5 years, respectively. The drinkers were younger (~5 years) and less obese than the non-drinkers. Most of the subjects were married, and slightly more of the drinkers were single. Fewer children (2·4 of non-drinkers vs. 2·1 of drinkers) and greater rates of oral contraceptive use were observed in the drinkers (18% of non-drinkers vs. 23% of drinkers). The drinkers were more educated than the non-drinkers, and more of the drinkers were also smokers (4% of non-drinkers vs. 15% of drinkers). The drinkers had a higher rate of HR-HPV infection than the non-drinkers (9% and 11% of non-drinkers and drinkers, respectively).

Alcohol consumption and the risk of HR-HPV infection

Current drinkers (OR 1·21, 95% CI 1·07–1·41) and those with a higher frequency of drinking (2–4 times/month: OR 1·28, 95% CI 1·04–1·56; ⩾2 times/week: OR 1·31, 95% CI 1·05–1·64; P for trend = 0·049) had higher risks of HR-HPV infection than the non-drinkers (Table 2). Women with a drinking habit for ⩾5 years had a higher risk of HR-HPV infection (OR 1·20, 95% CI 1·01–1·36) than those with a <5-year drinking habit. Increased consumption of the alcoholic beverages beer and soju was associated with increased risk of HR-HPV infection (P for trend <0·001 and <0·006 for glasses of beer or soju normally consumed; ⩾3 glasses of soju: OR 1·24, 95% CI 1·03–1·68).

Table 2. Odds ratios for persistent infection of high risk-human papillomavirus (HPV)

The subject number for each characteristic is based on the available data rather than all 9230 subjects who answered the indicated questions.

* Enrolment prevalence indicates the HR-HPV infection at the time of enrolment (vs. HR-HPV negativity at enrolment).

1-year and 2-year HR-HPV persistence were defined as HPV positivity in the 1-year follow-up study year and as HPV positivity in both the 1- and 2-year follow-up study years, respectively, after enrolment with HR-HPV positivity (vs. 1- and 2-year HR-HPV negatives defined as HR-HPV negativity for 1 and 2 consecutive years, respectively, after enrolment with HR-HPV negativity).

Odds ratios and 95% confidence intervals were calculated using a multivariate logistic regression analysis (adjusted for age, BMI, marital status, number of children, menopausal status, oral contraceptive use, education level, income level, and smoking status as categorical variables).

§ The P value is for the linear trend of multivariate odds ratios (adjusted for age, BMI, marital status, number of children, menopausal status, oral contraceptive use, education level, income level, and smoking status as categorical variables).

Usual amount is defined as the amount of beer or soju (in glasses) normally consumed per occasion.

|| Soju is a popular alcoholic beverage in Korea with a pure alcohol content (%) about 4–5 times greater than that of beer.

Alcohol consumption and 1- and 2-year HPV persistence

Compared to non-drinkers, the current alcohol drinkers had higher risks of 1- and 2-year HR-HPV persistence; the OR of current drinkers was 1·56 (95% CI 1·09–2·24) for the risk of 1-year HR-HPV persistence (vs. 1-year HR-HPV negative) and 2·49 (95% CI 1·32–4·71) for the risk of 2-year HR-HPV persistence (vs. 2-year HR-HPV negative) (Table 2). Drinkers who consumed alcohol ⩾2 times/week had a higher risk of 1-year HR-HPV persistence (OR 1·80, 95% CI 1·01–3·36) than non-drinkers. Drinkers with a ⩾5-year drinking habit had higher risks of 1-year HR-HPV persistence (OR 1·77, 95% CI 1·19–2·62) and 2-year HR-HPV persistence (OR 2·33, 95% CI 1·17–4·63) than women with a <5-year drinking habit. The risk of 2-year HR-HPV persistence showed an increasing trend with more glasses of beer consumed (P for trend = 0·025), and in particular, drinkers who consumed ⩾3 glasses of beer had a threefold increased risk of 2-year HR-HPV persistence, compared to non-drinkers (OR 3·62, 95% CI 1·35–9·75).

Alcohol consumption and 2-year consecutive or alternate HR-HPV persistence

As shown in Figure 1, compared to non-drinkers, the alcohol drinkers had a higher risk of 2-year consecutive or alternate HR-HPV persistence (OR 2·68, 95% CI 1·10–6·51) (vs. 2-year consecutive HR-HPV clearance). Women who normally consumed ⩾2 glasses of beer or soju in a single occasion had a higher risk of 2-year consecutive or alternate HR-HPV persistence compared to those who consumed ⩽1 glass of these alcoholic beverages (OR 2·90, 95% CI 1·06–7·98). The drinking duration (⩾5 years) and frequency (⩾2 times/month) demonstrated an increasing trend for the risk although these differences were not significant (OR 1·87, 95% CI 0·71–4·92 and OR 2·60, 95% CI 0·80–8·42, respectively).

Fig. 1. Odds ratios for 2-year consecutive or alternate high-risk human papillomavirus persistence associated with the characteristics related to alcohol consumption such as ‘alcohol drinkers’ (non-drinkers vs. drinkers); ‘usual amount of alcoholic beverages’ [2 glasses (50 ml/glass) of beer or soju vs. ⩾2 glasses]; ‘duration of drinking’ (<5 years vs. ⩾5 years); and ‘frequency of drinking’ (<2 times/month vs. ⩾2 times/month). A multivariate logistic regression analysis was performed after adjustment for age, body mass index, education level, and the number of children.

DISCUSSION

Our findings demonstrated that alcohol consumption and its associated behaviours, including the frequency of alcohol consumption, duration of drinking habit, and amount of alcoholic beverages consumed increased the risk of 1- and 2-year HR-HPV persistence (vs. 1- and 2-year HR-HPV negatives). Alcohol consumption and a high regular consumption of alcoholic beverages increased the risk of 2-year consecutive or alternate HR-HPV persistence (vs. 2-year consecutive HR-HPV clearance after enrolment with HR-HPV positivity).

Although alcohol has been reported as a potential risk factor of cervical cancer and HPV infection [2, 13], no studies have investigated the association between specific alcohol behaviours and HPV persistence in the cervix. Our study is the first to demonstrate a significant association between cervical HPV persistence and alcohol consumption. In a few previous studies reporting on epidemic co-factors in natural HPV infection histories, alcohol consumption increased the risk of 36-month HPV infection in college-aged young women, but alcohol was not presented as a risk factor for persistent HPV infections at ⩽6 months [2]. Goodman et al. reported that cervical HPV acquisition increased with alcohol consumption among sexually active multi-ethnic women, aged 18–85 years, who were recruited from Hawaii, but cervical HPV clearance did not correlate with alcohol consumption [13]. In contrast to the lack of studies on alcohol and HPV persistence, several cervical cancer cohort studies have been conducted with respect to alcoholics or alcoholism [1517]. A single large-scale population-based cohort study assessed the association between moderate alcohol intake and the total incidence of cancer among women in the UK, but no significant association was found with cervical cancer [18].

A critical point is that the drinkers in our cohort had a light-to-moderate level of alcohol consumption; the mean daily alcohol amount consumed by the drinkers (6·0 ± 9·5 g/day) was within the range of light-to-moderate alcohol consumption for Korean women (1·0–14·9 g/day [19]). Additionally, drinking of beer, a mild type of alcohol (the rates of pure alcohol in beer and soju are 4·5% and 21%, respectively) showed the highest risk of HPV persistence with a regular consumption of ⩾3 glasses of beer. Daily alcohol consumption had a relatively high level in our subjects, but this is included in a moderate alcohol consumption level. The benefits of moderate alcohol consumption have been suggested by several health outcomes, but to date, controversies and inconsistent findings exist [20]. As reported in a recent meta-analysis that investigated the relationship between alcohol consumption and the mortality risk of all cancers, a J-shaped association was found in men but not in women [21]. In a large-scale prospective study of Korean men and women, light-to-moderate alcohol consumption was associated with lower mortality risks from all causes and from cancer in men, but did not show favourable effects on the risks in women [19]. Members of Asian populations frequently present with a slow-metabolizing acetaldehyde dehydrogenase variant [22]. Furthermore, there are gender differences in alcohol pharmacokinetics and alcohol-related comorbidities [23]. Therefore, the genetic susceptibility of Asian women to alcohol might differ from that of other populations with respect to defence against viral infection or viral clearance.

There are potential direct mechanisms to support a positive association between alcohol and HPV persistence. Alcohol can induce folate deficiency by reducing the absorption of folate in the colon and thus induce DNA hypomethylation [24]. In fact, folate is a plausible protective factor against cervical cancer [25] and high levels have potential effects against the initiation of HPV-related dysplasia [26, 27]. Additionally, alcohol activates cytochrome P450 2E1 which leads to the production of reactive oxygen species (ROS) [28], and various antioxidant enzymes and detoxifying pathways are consistently associated with HPV-transformed cells [29]. As reported in several studies, cervical ROS could contribute to a divergent host response against the viral infection because of highly variable concentrations of amines and amine oxidases in the cervical mucus [30]. Moreover, women with high ferritin levels were less likely to clear HR-HPV due to the increased generation of ROS than those with lower levels [31]. The immune system is important in viral disease, but the mechanisms that influence specific host immunity against HPV remain unclear [32].

In our study, the frequency of current drinkers in the subjects (45·4%) was higher than the overall frequency of drinkers (20·3%) among Korean women [19]. The reason for the higher rate of light-to-moderate alcohol drinkers in this study might be the higher socioeconomic status of our subjects, as determined by factors such as household income. Compared to the mean monthly household income in Korea (about 199 and 386 million won in 2001 and 2011, respectively) [33], our subjects had a higher income level (about 390 million won). It is a known fact that lower socioeconomic groups are at a higher risk of binge- or heavy drinking, while higher socioeconomic groups are associated with a higher frequency of light drinking [34, 35]. Furthermore, the drinkers in our subject cohort were characterized as younger, more likely to smoke, and more likely to use oral contraceptives compared to non-drinkers. Although a regression analysis was performed after sufficiently adjusting for these characteristics, undisclosed social factors of the moderate drinkers or the complex natures of these factors could influence the risk of HPV persistence.

This study has some limitations. Sexual activity could not be considered as a confounding factor for HPV infection because of the absence of sexual behaviour-related questions in the health screening questionnaire. The mean age of our study subjects was 48 years (⩾40 years: 81%). A reduced sexual interest and desire along with a reduced frequency of sexual intercourse have been reported among middle-aged women [36]. About 89% and 71% of Korean women aged 40–49 and 50–59 years, respectively, reported having an inactive sexual life and the highest sexual intercourse frequency was once/month in those aged 40–49 years [37]. However, the incidence of cervical cancers in Korea was highest in middle-aged women (35–64 years). Sexual behaviours in this population might not greatly affect the association found in the study. Second, persistent HPV infection was defined according to the HC-II HPV genotype pooling method rather than HPV genotype-specific detection. However, it was reported that 1-year HPV persistence as detected by HC-II is more sensitive and predictive for CIN-3 than determination of genotype-specific persistence by linear blot assay [38, 39]. The pooled detection of multiple oncogenic HPV genotypes can also minimize false-negative errors [39]. Furthermore, about 86·3% of Korean women had one or two sexual partners in their lifetimes [40, 41] and 91·3% did not report having new sexual partners in the past 6 months [41]. Persistent HPV infection with the same genotype is highly probable.

In conclusion, this study demonstrates that light-to-moderate alcohol consumption or related behaviours may increase the risk of cervical HR-HPV persistence and infection. These increases may be caused by the direct harmful effects of alcohol on the cervix, or the combination of alcohol consumption, and the social behaviours of female moderate drinkers. We suggest that more studies that investigate the correlation between moderate alcohol consumption and HR-HPV persistence should be performed, particularly in Korean women.

ACKNOWLEDGEMENTS

We are grateful to Dr Jung Sun Kim for supplying data from the health screening examinees and sincerely appreciate the 10440 women who participated in this study. This research was supported by grants (1110320, 1310360, 0910221) from the National Cancer Center in Korea.

DECLARATION OF INTEREST

None.

REFERENCES

1. Schiffman, MH, et al. Epidemiologic evidence showing that human papillomavirus infection causes most cervical intraepithelial neoplasia. Journal of the National Cancer Institute 1993; 85: 958964.
2. Ho, GY, et al. Natural history of cervicovaginal papillomavirus infection in young women. New England Journal of Medicine 1998; 338: 423428.
3. Schiffman, M, et al. Human papillomavirus and cervical cancer. Lancet 2007; 370: 890907.
4. de Freitas, AC, et al. Susceptibility to cervical cancer: an overview. Gynecologic Oncology 2012; 126: 304311.
5. de Araujo Souza, PS, Sichero, L, Maciag, PC. HPV variants and HLA polymorphisms: the role of variability on the risk of cervical cancer. Future Oncology (London, England) 2009; 5: 359370.
6. Lai, CH, et al. Host and viral factors in relation to clearance of human papillomavirus infection: a cohort study in Taiwan. International Journal of Cancer 2008; 123: 16851692.
7. Schmeink, CE, et al. Human papillomavirus persistence in young unscreened women, a prospective cohort study. PLoS ONE 2011; 6: e27937.
8. Hibma, MH. The immune response to papillomavirus during infection persistence and regression. Open Virology Journal 2012; 6: 241248.
9. Nielsen, A, et al. Persistence of high-risk human papillomavirus infection in a population-based cohort of Danish women. Journal of Medical Virology 2010; 82: 616623.
10. Anon. IARC monographs on the evaluation of carcinogenic risks to humans: Alcohol consumption and ethyl carbamate. Lyon, France: WHO, IARC; 20101017–1606 (print), 1017–1606 (linking) (series 2010/01/01).
11. Rod, NH, et al. Low-risk factor profile, estrogen levels, and breast cancer risk among postmenopausal women. International Journal of Cancer 2009; 124: 19351940.
12. Hjartaker, A, Meo, MS, Weiderpass, E. Alcohol and gynecological cancers: an overview. European Journal of Cancer Prevention 2010; 19: 110.
13. Goodman, MT, et al. Prevalence, acquisition, and clearance of cervical human papillomavirus infection among women with normal cytology: Hawaii Human Papillomavirus Cohort Study. Cancer Research 2008; 68: 88138824.
14. Solomon, D, et al. The 2001 Bethesda System: terminology for reporting results of cervical cytology. Journal of the American Medical Association 2002; 287: 21142119.
15. Sigvardsson, S, et al. Increased cancer risk among Swedish female alcoholics. Epidemiology 1996; 7: 140143.
16. Weiderpass, E, et al. Alcoholism and risk for cancer of the cervix uteri, vagina, and vulva. Cancer Epidemiology, Biomarkers and Prevention 2001; 10: 899901.
17. Adami, HO, et al. Alcoholism and cancer risk: a population-based cohort study. Cancer Causes and Control 1992; 3: 419425.
18. Allen, NE, et al. Moderate alcohol intake and cancer incidence in women. Journal of the National Cancer Institute 2009; 101: 296305.
19. Kim, MK, Ko, MJ, Han, JT. Alcohol consumption and mortality from all-cause and cancers among 1·34 million Koreans: the results from the Korea national health insurance corporation's health examinee cohort in 2000. Cancer Causes and Control 2010; 21: 22952302.
20. Nova, E, et al. Potential health benefits of moderate alcohol consumption: current perspectives in research. Proceedings of the Nutrition Society 2012; 71: 307315.
21. Jin, M, et al. Alcohol drinking and all cancer mortality: a meta-analysis. Annals of Oncology 2013; 24: 807816.
22. Druesne-Pecollo, N, et al. Alcohol and genetic polymorphisms: effect on risk of alcohol-related cancer. Lancet Oncology 2009; 10: 173180.
23. Baraona, E, et al. Gender differences in pharmacokinetics of alcohol. Alcoholism, Clinical and Experimental Research 2001; 25: 502507.
24. Sanjoaquin, MA, et al. Folate intake and colorectal cancer risk: a meta-analytical approach. International Journal of Cancer 2005; 113: 825828.
25. Powers, HJ. Interaction among folate, riboflavin, genotype, and cancer, with reference to colorectal and cervical cancer. Journal of Nutrition 2005; 135 (12 Suppl.): 2960S2966S.
26. Piyathilake, CJ, et al. Indian women with higher serum concentrations of folate and vitamin B12 are significantly less likely to be infected with carcinogenic or high-risk (HR) types of human papillomaviruses (HPVs). International Journal of Women's Health 2010; 2: 712.
27. Ferguson, AW, Svoboda-Newman, SM, Frank, TS. Analysis of human papillomavirus infection and molecular alterations in adenocarcinoma of the cervix. Modern Pathology 1998; 11: 1118.
28. Poschl, G, et al. Alcohol and cancer: genetic and nutritional aspects. Proceedings of the Nutrition Society 2004; 63: 6571.
29. De Marco, F. Oxidative Stress and HPV Carcinogenesis. Viruses 2013; 5: 708731.
30. Fernandez, C, et al. Evaluation of the significance of polyamines and their oxidases in the aetiology of human cervical carcinoma. British Journal of Cancer 1995; 72: 11941199.
31. Siegel, EM, et al. Circulating biomarkers of iron storage and clearance of incident human papillomavirus infection. Cancer Epidemiology, Biomarkers and Prevention 2012; 21: 859865.
32. Einstein, MH, et al. Clinician's guide to human papillomavirus immunology: knowns and unknowns. Lancet Infectious Diseases 2009; 9: 347356.
33.Anon. Average monthly income and expenditure. Korean Statistical Information Service: Statistics Korea, 2013 (http://kosis.kr/index/index.jsp).
34. Crum, RM, et al. The risk of alcohol abuse and dependence in adulthood: the association with educational level. American Journal of Epidemiology 1992; 135: 989999.
35. Thun, MJ, et al. Alcohol consumption and mortality among middle-aged and elderly U.S. adults. New England Journal of Medicine 1997; 337: 17051714.
36. Park, YJ, et al. Sexuality and related factors of postmenopausal Korean women. Taehan Kanho Hakhoe chi 2003; 33: 457463.
37. Yoon, H, et al. Questionnaire based evaluation of sexual activity and sexual dysfunction in Korean women. Korean Journal of Urology 2001; 42: 102–114.
38. Gage, JC, et al. Comparison of measurements of human papillomavirus persistence for postcolposcopic surveillance for cervical precancerous lesions. Cancer Epidemiology, Biomarkers & Prevention 2010; 19: 16681674.
39. Marks, MA, et al. Evaluation of any or type-specific persistence of high-risk human papillomavirus for detecting cervical precancer. Journal of Clinical Microbiology 2012; 50: 300306.
40. Kim, JW, et al. Factors affecting the clearance of high-risk human papillomavirus infection and the progression of cervical intraepithelial neoplasia. Journal of International Medical Research 2012; 40: 486496.
41. Yoo, KY, et al. Risk factors associated with uterine cervical cancer in Korea: a case-control study with special reference to sexual behavior. Journal of Epidemiology 1997; 7: 117123.