International Journal of Molecular Medical Science, 2024, Vol.14, No.5, 264-273 http://medscipublisher.com/index.php/ijmms 3 underlying molecular alterations, such as genetic or epigenetic changes that drive cervical carcinogenesis (Liang et al., 2021). This limitation can be especially problematic in the early stages of cervical cancer development, when cellular changes may not yet be apparent. Consequently, there is a growing recognition of the need for more sensitive and specific screening tools, such as genetic marker-based methods, which could complement or even replace cytology-based screening to improve early detection and reduce the burden of cervical cancer. 2.2 HPV DNA testing Human papillomavirus (HPV) DNA testing has become a crucial part of cervical cancer screening due to the established role of high-risk HPV types in its development (Sabeena et al., 2020). This test detects the presence of DNA from high-risk HPV strains in cervical cells, helping to identify women at increased risk for developing cervical intraepithelial neoplasia (CIN) and cervical cancer (Zhang et al., 2022). HPV DNA testing has shown superior sensitivity compared to cytology-based methods, with sensitivity rates exceeding 90% for detecting CIN2+ lesions (Thomsen et al., 2021). This high sensitivity makes HPV DNA testing an invaluable tool for identifying at-risk women, facilitating earlier intervention and treatment. Additionally, HPV DNA testing can serve as a primary screening method or as a triage option following an abnormal cytology result, thereby enhancing the overall effectiveness of the screening strategy. One major advantage of HPV DNA testing is its ability to be conducted using self-collected samples, which has been shown to increase screening uptake, especially among populations with limited access to healthcare services or those less likely to participate in regular screening programs. Self-sampling methods, such as vaginal swabs, have proven to be highly acceptable and effective, offering a way to expand screening coverage in low-resource settings and among women hesitant to undergo clinician-collected sampling (Leeuwen et al., 2018). Additionally, the high negative predictive value of HPV DNA testing allows for longer screening intervals, easing the burden on healthcare systems and reducing the frequency of invasive procedures for women with negative results. However, while HPV DNA testing significantly enhances the detection of high-risk cases, its relatively low specificity can lead to the identification of transient HPV infections that may never progress to cancer (Gaisa et al., 2021). This limitation highlights the need for complementary triage methods, such as genetic or epigenetic markers, to better identify women at the highest risk of developing cervical cancer. 2.3 Limitations of traditional screening methods Despite the widespread use of Pap smears and HPV DNA testing in cervical cancer screening programs, both methods have significant limitations that can affect their overall effectiveness. The Pap smear, while crucial in reducing the incidence and mortality of cervical cancer, has variable sensitivity, ranging from 50% to 75%. This variability depends on factors such as sample collection, slide preparation, and the expertise of the observer in cytological interpretation. As a result, false-negative results can occur, causing precancerous or cancerous lesions to be missed and delaying diagnosis and treatment. Additionally, the subjective nature of cytology interpretation means the Pap smear may overlook subtle cellular changes, particularly in the early stages of carcinogenesis, when molecular alterations have yet to manifest as visible abnormalities (Comparetto and Borruto, 2021). Consequently, while the Pap smear is effective for detecting established lesions, it may be less reliable for early detection of cervical cancer at the molecular level. HPV DNA testing, in contrast, provides higher sensitivity for detecting high-risk HPV infections linked to cervical cancer. However, this increased sensitivity comes with a trade-off: reduced specificity. HPV DNA testing can identify transient HPV infections, which are common and often resolve on their own without causing significant disease (Zhang et al., 2022). As a result, a positive HPV test does not necessarily indicate an immediate risk of developing cervical cancer, leading to a high rate of false positives. This can result in unnecessary follow-up procedures, such as colposcopies and biopsies, which increase healthcare costs and may cause both physical and psychological distress for patients. Moreover, while HPV testing is effective at detecting high-risk HPV types, it does not provide information about the subsequent genetic and epigenetic changes in host cells that drive cancer progression. Therefore, while traditional screening methods like Pap smears and HPV DNA testing are vital components of current cervical cancer prevention strategies, they have inherent limitations that
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