Cervical mucus biomarkers could improve early detection of cervical cancer

Cervical cancer is a highly prevalent cancer, with approximately 500,000 new cases diagnosed each year. Shockingly, the number of individuals diagnosed with precursor lesions in the cervix-;also known as cervical intraepithelial neoplasia (CIN)-;is 20 times higher. As with many potentially malignant conditions, early diagnosis of cervical cancer can make all the difference in a patient's life in terms of treatment outcomes. For this, developing effective, convenient, and easily available screening protocols for CIN and cervical cancer is of paramount importance.

Currently, the two most widely used screening procedures for these conditions are human papillomavirus (HPV) test and cytology examination. While cytology is well established as a screening method in many countries, it has rather low sensitivity for detecting CIN. On the other hand, HPV tests are highly sensitive, but HPV infections do not always lead to cervical lesions, resulting in poor specificity. Given these drawbacks, the need for improved diagnostic methods is all the more necessary. 

Against this backdrop, a research team led by Professor Takuma Fujii from Fujita Health University, Japan, aimed to identify biomarkers that could assist in the early detection of cervical cancer. In their latest paper published in Cancer Science on May 15, 2024, they report on a series of compounds that show abnormal expression in serum and cervical mucus samples of cervical cancer patients. These findings could potentially revolutionize disease prevention strategies. 

Interestingly, the use of cervical mucus samples as part of a potential diagnostic tool was not initially planned. "We wanted to investigate how changes in local immunity are related to cervical cancer, and so, we aimed to study all the currently known microRNAs (miRNAs) associated with the development and progression of cervical tumors," explains Fujii. Adding further, Fujii says, "Initially, we focused on developing a serum-based diagnostic method for clinical use. However, we realized it would be better to first verify if molecular expression levels in the local tissue correlated with serum, assessing the feasibility of a serum diagnostic method."

To achieve these goals, the research team compared the miRNA and cytokine profiles from serum and mucus samples. These were collected from patients with cervical cancer or CIN who underwent routine gynecological examinations at Fujita Health University Hospital, over approximately eight years. Through initial screening, the researchers identified three candidate miRNAs and five candidate cytokines in serum, and five candidate miRNAs and seven candidate cytokines in mucus.

With the help of miRNA real-time PCR tests and cytokine immunoassay experiments on a larger sample size, the team verified the abnormal expression of these biomarkers on patients with cervical cancer at different stages of the disease. They subsequently evaluated the diagnostic potential of these compounds. Surprisingly, while miRNAs and cytokines in serum showed limited diagnostic accuracy, a specific combination of miRNAs and cytokines in mucus samples proved much more promising. This suggests that focusing on changes in local expression levels, rather than serum levels, may offer a superior diagnostic strategy.

"Our study, for the first time, demonstrates that analyzing mucus samples can distinguish cervical tumors from normal tissues more accurately than serum samples. Using such a method as an additional option to traditional screening techniques could help discover cancer and precancerous conditions at an earlier stage," remarks Fujii.

Going ahead, however, further validation on larger populations is necessary to solidify these findings and pave the way for improved cervical cancer screening and diagnostic procedures. These advancements could reduce the need for invasive procedures such as colposcopy, which, in turn, would reduce the burden on patients and minimize healthcare costs.

Here's hoping that with continued progress, early detection of cervical cancer becomes feasible, sparing women from the burden of this devastating disease.