Background

World over, there were 770,828 incident cervical cancer cases in 2020 [1]. Cervical cancer is ranked the second most common cancer among women of reproductive age [2] and it accounts for more than 270 000 deaths annually, mostly in developing countries [3] and most especially in sub Saharan Africa [4, 5]. In the East African region, Cervical Cancer stands at 43/100,000 cancer cases [6], and over 4,000 new cases are recorded annually in Uganda [7]. A well-proven way to prevent cervical cancer is to screen and detect pre-cancers (CIN) before progressing to invasive cancer [3]. Other methods of cervical cancer prevention include vaccination for girls aged 9 to 14 years, health education for both boys and girls as well as treatment for all that need to be treated [1, 8, 9]. Vaccination as well as other factors has also been reported to be synergic to treatment [10] and it has an impact on the risk of developing persistence and recurrence of cervical dysplasia after treatment [11,12,13].

Cervical intraepithelial neoplasia (CIN) represents a precancerous stage that develops before cervical cancer [14, 15] and is mainly a result of infection with High Risk Human Papilloma Virus (HRHPV) [16]. Preventing CIN is still the best approach to eliminating the cervical cancer burden [17, 18].

It is important to understand other risk factors to CIN as this may lead to more targeted primary prevention strategies to address the current cervical cancer burden [14]. There are secondary factors that lead to HPV infection, its persistence and development of precancerous lesions [19].

An increased BMI has been associated with a number of disease conditions ranging from cardiovascular diseases (CVD) to cancers [20]. Obesity has been thought to increase one’s risk of developing cervical cancer [21]. It is hypothesised that increased BMI tends to impair one’s immune system, leading to persistent HPV infections, leading to cervical cancer [22,23,24]. The odds of having CIN are said to be higher for those women with increased BMI [14]. Obesity has previously been shown to be associated with increased cervical cancer risk [25,26,27,28,29]. However, in a broader picture, the association between BMI and CIN is not well understood [21, 30, 31]. This study was therefore aimed at determining if there is an association between obesity and cervical intraepithelial neoplasia.

Materials and methods

Study setting

The study was carried out among women attending the cervical cancer clinic of Mbarara Regional Referral Hospital. This clinic screens an average of 15 mothers per day and operates five days a week. It serves 13 districts of south western Uganda. The confirmatory tests for cervical intraepithelial lesions, PAP smears or histology are performed in the pathology department of the hospital/university.

Study design

This was an unmatched case control study. It included all women who sought cervical cancer screening services at the cervical cancer clinic of Mbarara Regional Referral Hospital. The cases were those women with a positive VIA and confirmed, with Pap smear cytology or histology, to have CIN while controls were those women with a negative VIA.

Sampling procedure

Cases and controls were selected prospectively. Cases were recruited using purposive sampling. Then we employed the incidence density sampling method to obtain controls i.e. we recruited a control each time a case was identified.

Sample size determination

The sample size was calculated using an online software, OpenEpi, Version 3, Open source calculator-SSCC. OpenEpi - Sample Size for Unmatched Case-Control Studies.

For this calculation, we considered a two-sided confidence level (1-alpha) of 95, a study power of 80%, a case to control ratio of 1, a proportion of cases with obesity as a component of metabolic syndrome of 40.99% [32] and a proportion of controls with obesity as a component of metabolic syndrome of 18.8% [33]. We also used the least extreme odds ratio of 3.0. This gave a minimum of 75 cases and 75 controls, considering module of Fleiss with continuity correction [34].

Data collection

Demographic data collection

Demographic data was collected using a pretested enrolment form which was administered by research assistants, the cervical cancer clinic midwives. Participants were explained to and taken through the consent process, filling the enrolment form and anthropometric measurements. The study PI performed random daily checks on the procedures to ensure conformity to the study requirements and validity as well as completeness of the data. Data collected included age, region of residence, age at first sexual debut, family planning usage, HIV status, CD4 count, HIV viral load, highest level of education, number of life-time sexual partners, marital status, history of blood pressure and history of diabetes.

Body Mass Index and anthropometric measurements

Measurements of height (in meters) and weight (in kilograms) were taken using calibrated stadiometer and weighing scale respectively. We also measured waist circumference (in meters). We calculated BMI as the weight in kilograms divided by the square of the height in meters. We then categorized BMI as non-obese (< 30 kg/m2) or obese (30 ≤ kg/m2) in accordance with standard cut off points by the World Health Organisation as used in previous studies [35, 36]. We defined central obesity using the World Health Organisation categorisation, as a waist to height ratio of ≥ 0.5 [35, 36].

Data management and analysis

Data was collected by the research assistants and the Principal Investigator. It was then entered into Microsoft Excel (Ms 2007), computer database, imported and analysed using STATA 17 software. Descriptive statistics were used to characterize the population using frequencies, means ± standard deviations (SDs) using the Ind. t test. Chi-square, Fisher’s exact test and logistic regression analysis were used to describe categorical variables and assess associations between obesity and categorical variables. Univariate analysis was done first and we purposively selected variables, with p-values < 0.1, for multivariate analysis. A P-value of ≤ 0.05 was considered to be statistically significant at multivariate analysis.

Eligibility criteria

We included all women of 21 years and above, who reported to the cervical cancer clinic of Mbarara Regional Referral Hospital during the time of the study, screened positive with VIA or HPV DNA, consented to participate in the study, and later confirmed to have a precancerous lesion (CIN) by either Pap smear or histology. Any woman that was moribund (too ill) to consent was excluded.

Results

We recruited a total of 188 women (94 controls and 94 cases), following our inclusion criteria. There were 36/94 controls with general obesity and 24/94 cases with general obesity. This resulted in the prevalence of general obesity among controls and cases of 38% and 26% respectively. Results from demographics show non-significant differences between cases and controls. However, mean age of participants, contraceptive used and highest level of education varied significantly across cases and controls. Table 1.

Table 1 Comparison of obesity and other demographic characteristics between women with and those without Cervical Intraepithelial Neoplasia
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Distribution of participant demographics with general obesity

The primary exposure of this study was obesity among participants with or without CIN. From all study participants, 60 participants had obesity while 128 were non obese. We observed a statistically significant difference in the distributions of age groups, HIV viral load, contraceptive use and age at sexual debut across obesity. Table 2.

Table 2 Distribution of participant demographics based on general obesity
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Distribution of cytology results across general obesity

From the 60 study participants who had general obesity, 38.3% (23/60) were diagnosed with low grade squamous intraepithelial lesion. However, majority of low grade squamous intraepithelial lesions were diagnosed among non-obese women (45.3%). We observed a weakly significant distribution of cytology results across general obesity. Table 3.

Table 3 Distribution of cytology results based on general obesity
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Factors associated with general obesity among study participants

We performed logistic regression analysis, first at bivariate and then multivariate. We found that residence in Mbarara city and being in the age groups of 31–45 and 45 ≤ were significantly associated with general obesity among the study participants. Table 4.

Table 4 Factors associated with general obesity among study participants
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Association between obesity and grades of cervical intraepithelial neoplasia

Table 5 shows results from logistic regression analysis putting into account other demographic factors. General obesity did not show any statistically significant association with cervical intraepithelial neoplasia. University education and contraceptive usage were among the other factors that were significantly associated with cervical intraepithelial neoplasia.

Table 5 Logistic regression analysis showing association between general obesity and other factors and Cervical Intraepithelial Neoplasia
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Discussion

Obesity is one of the five components of metabolic syndrome that presents with unhealthy amounts and or distribution of fat in one’s body [37] and it is known to increase one’s chances of developing heart diseases and other non-communicable diseases including cervical cancer [38]. There is a reported increased mortality from cervical cancer among obese women [27]. Cervical cancer develops quite slowly, through precancerous stages called cervical intraepithelial neoplasia (CIN) [39]. Therefore, early detection of metabolic syndrome components in CIN is of great significance for prevention of heart and other related cardiovascular diseases.

To our knowledge, there is no other study that has reported prevalence and association between obesity and CIN in a Ugandan population. This study showed that the prevalence of general obesity was 26% among women with cervical intraepithelial neoplasia. General obesity, though not statistically significant, was more prevalent in participants with low grade squamous intraepithelial lesions (38.3%) compared with other grades but this observation was not statistically significant. Previous studies have equally found a similar finding [40]. The possible explanation for this high prevalence of obesity in CIN is that fact that there is an increased serum expression of sex hormones which themselves are thought to increase risk of cancer [41, 42].

This shows that much as many low grade squamous intraepithelial lesions regress on their own, there is an increased risk of coronary heart disease, diabetes, stroke and other cardiovascular diseases [38, 43,44,45] among patients with low grade squamous intraepithelial lesion due to obesity.

This study also showed that residing in Mbarara city and being in the age brackets of 31–45 and ≥ 46 were significantly associated with obesity among the study participants. It is important to note that the study site, Mbarara Regional Referral Hospital is located in Mbarara city, an urban city in South western Uganda with a relatively high socioeconomic status, and it contributed a big fraction of study participants. This could partly explain the high prevalence of obesity and its association with region of residence, since there is an association between obesity and a high socioeconomic status [46,47,48]. Similar findings about age and obesity were reported in a Nigerian population [49].

We did not find any association between obesity and cervical precancerous lesions. There have been a lot of inconsistencies in reported studies on association between obesity and CIN or cervical cancer [21, 25,26,27,28, 42, 50, 51]. However, our observation is consistent with some previous studies which have shown that obesity is not associated with cervical cancer or its precancerous lesions [21, 25,26,27,28,29, 42, 50]. For instance, a systematic review by Poorolajal et al. [21] only revealed a weak association between obesity and cervical cancer. A lower risk of CIN and higher risk of cervical cancer was reported among obese women [52] and this observation was attributed to a low detection rate of CIN among obese women [53, 54]. Similarly, a study among Thai women showed an increased prevalence of abnormal Pap smear results among obese women though not statistically significant [40].

To the contrary, an association between increased body mass index and a reduce risk of precancerous lesions was reported in a prospective cohort of Koreans [51]. Specifically, from a cross sectional study conducted in a Nigerian population, there was a reported association between obesity and epithelial cell abnormalities [49].

Strengths and limitations

We acknowledge that our study did not have a big sample size and this might have hindered observation of associations between variables. We also did not capture information on participant HPV vaccination status. Our current guidelines dictate vaccination of only young girls (9–14 years). In any case, we did not expect adults in our study to have been vaccinated considering the fact that HPV vaccination is a new intervention that has just been rolled out.

Conclusion

There was a high prevalence of obesity among women with CIN especially low grade squamous intraepithelial lesions. We did not observe any statistically significant association between obesity and CIN. Factors associated with obesity among our study participants included residence in Mbarara city and being in the age groups of 31–45 and ≥ 45 years. This emphasises the need to rethink management of CIN and cervical cancer to control other non-communicable diseases that could arise due to obesity. We recommend prospective cohort studies to further understand obesity and CIN as well as cervical cancer.