The findings of our study indicate a notable association between diabetes mellitus and an increased risk of positive findings in pap smear tests, suggesting that diabetic females may be more susceptible to cervical cytological abnormalities compared to their non-diabetic counterparts (OR 6.55). This association may be explained by several biological mechanisms. Diabetes is known to affect the immune system, potentially compromising the body’s ability to clear human papillomavirus (HPV) infections, a known risk factor for cervical cancer. The impaired immune response, characterized by reduced activity of natural killer cells and delayed adaptive immune responses, may allow HPV infections to persist longer and progress to more severe cellular changes [21]. Additionally, hyperglycaemia can contribute to chronic inflammation, which may play a role in the development of cervical abnormalities [22]. Elevated glucose levels can induce oxidative stress and facilitate an environment conducive to oncogenesis, thereby increasing the likelihood of cervical carcinoma progression. The above findings are in solidarity with other recent studies [23].

Our study has also unveiled a possible link between diabetes and an increased risk of both human papillomavirus (HPV) infection and cervical cancer through the shared genetic factors underlying these conditions. This finding carries certain implications for understanding the complex interplay between diabetes, HPV infection, and cervical cancer development. The gene COL11A2P1, closely linked to HLA-DPB2 and strongly associated with cervical cancer and early age of onset for DM, is located on Chromosome 6 [24]. Studies suggest its involvement in immune-related pathways and inflammatory responses, which may influence both cancer progression and diabetes development. INS-IGF2, located on chromosome 11, is a read-through gene and paralog of the INS gene, which encodes for insulin [25]. It is involved in the AMPK signalling pathway, a critical regulator of energy balance and metabolism, which is being evaluated for its role in tumour suppression and insulin regulation, linking metabolic disorders to cancer biology. The A allele of the gene TTC7B is strongly linked to cervical cancer, particularly poor response to platinum-based therapy for cervical carcinoma [26]. It is also associated with severe autoimmune diabetes type 2, likely due to its influence on immune system dysregulation. This may contribute to explaining poor response to chemotherapy in some cervical carcinoma patients with diabetes, as it could exacerbate tumour resistance. SILC1, located on chromosome 2, is associated with CIN grade 2/3 and gastric cancer [27]. This gene, involved in regulating cellular invasiveness and proliferation, is also linked to type 2 diabetes, with evidence suggesting it may mediate shared pathways that predispose individuals to both conditions.

Our research has identified specific genetic variants that are associated with an elevated risk of developing both diabetes and susceptibility to HPV infection and cervical cancer. This finding suggests possibility of a common genetic basis that may predispose individuals to these seemingly unrelated conditions. Genetic studies have previously highlighted the importance of certain loci in both diabetes [15,16,17] and cervical cancer [13, 14], but our study is among the first to demonstrate shared genetic links. The shared genetic factors between diabetes, HPV infection, and cervical cancer may be indicative of underlying biological mechanisms. For instance, genetic variants associated with diabetes could influence the immune response, potentially impairing the body’s ability to clear HPV infections, a known precursor to cervical cancer. Additionally, these variants may play a role in the progression of cervical abnormalities to cancerous stages. Functional validation studies evaluating impact on development of both the disorders can play an important role in establishing the association.

Cervical cancer remains a global public health concern, and diabetes is a widespread chronic condition. Understanding the link between the two is crucial for healthcare providers and policymakers. Our study contributes to the growing body of evidence supporting the need for comprehensive healthcare management that considers not only diabetes but also its potential implications on other health outcomes. This discovery has significant implications for both diabetes management and women’s health, and it warrants careful consideration in the context of preventive healthcare strategies and personalized screening protocols along with potential avenues for targeted prevention and management strategies. For instance, firm establishment of association with further studies can guide clinicians to recommend diabetic females opt for cervical screening more frequently than their non-diabetic counterparts. This is particularly important in regions where diabetes incidence is rising and no established public health screening programmes for cervical pathologies exist or there is lack of awareness among general population.

While our study provides valuable insights, it is not without limitations. We acknowledge that confounding factors like smoking status, lack of genetic data from diverse population and unavailability of glycaemic control status data, may influence the observed association. Because smoking itself is a major risk factor for cervical cancer and poor glycaemic control is well known to predispose towards increased risk of infection and oxidative damage, both the factors can potentially affect pathologic findings. The GWAS data are lacking from resource limited regions, and hence, current analysis is based on genetic data available from a less diverse population. Genetic data are primarily available from European, East Asian, African American ethnicities and sparsely from South Asian ethnicities; this can limit generalization of the association found in this study. Future research should incorporate larger and more diverse cohorts, as well as longitudinal studies, to confirm and further explore these findings. The study could not identify specific snRNPs due to technical limitations. Additionally, investigating the impact of glycaemic control and diabetes duration on cervical pathologies could provide deeper insights into the relationship. While our study presents a noteworthy revelation, further prospective research, particularly functional validation studies, is needed to unravel the precise mechanisms by which these shared genetic factors contribute to the risk of developing both conditions.