Abstract
Cervical cancer is the fourth most common neoplasia in women and the infection with human papilloma virus (HPV) is its necessary cause. Screening methods, currently based on cytology and HPV DNA tests, display low specificity/sensitivity, reducing the efficacy of cervical cancer screening programs. Herein, molecular signatures of cervical cytologic specimens revealed by liquid chromatography-mass spectrometry (LC-MS), were tested in their ability to provide a metabolomic screening for cervical cancer. These molecules were tested whether they could clinically differentiate insignificant HPV infections from precancerous lesions. For that, high-grade squamous intraepithelial lesions (HSIL)-related metabolites were compared to those of no cervical lesions in women with and without HPV infection. Samples were collected from women diagnosed with normal cervix (N = 40) and from those detected with HSIL from cytology and colposcopy (N = 40). Liquid-based cytology diagnosis, DNA HPV-detection test, and LC-MS analysis were carried out for all the samples. The same sample, in a customized collection medium, could be used for all the diagnostic techniques employed here. The metabolomic profile of cervical cancer provided by LC-MS was found to indicate unique molecular signatures for HSIL, being two ceramides and a sphingosine metabolite. These molecules occurred independently of women’s HPV status and could be related to the pre-neoplastic phenotype. Statistical models based on such findings could correctly discriminate and classify HSIL and no cervical lesion women. The results showcase the potential of LC-MS as an emerging technology for clinical use in cervical cancer screening, although further validation with a larger sample set is still necessary.
Highlights
Cervical cancer is the fourth most common neoplasia in women, and the seventh overall
Cervical cytologic samples were obtained from women from two groups: (i) 40 women undergoing gynecological examination in the family planning clinic (FPC) from the Women’s Hospital “Prof. Dr José Aristodemo Pinotti”—CAISM-UNICAMP, previously diagnosed with normal cervix in the clinical evaluation and (ii) 40 women undergoing to a loop electrosurgical excision procedure (LEEP) due to previous detected high-grade squamous intraepithelial lesions (HSIL) from cytology and colposcopy, in the surgical service from CAISM-UNICAMP
Considering the results for cytology and histology for HSIL subjects, there was an agreement of 91% (35 HSIL subjects confirmed via histology)
Summary
Cervical cancer is the fourth most common neoplasia in women, and the seventh overall. In Brazil, the last survey highlighted cervical cancer as the fourth most common cancer with 7.9% incidence and the projections for the biannual period 2016–2017 is the incidence of 47,400 new cases [2]. Among the high-risk HPV, HPV16 and HPV18 are responsible for 70% of all the cervical cancer cases [3, 5]. Cervical lesions generated by HPV infection are classified according to lower anogenital squamous terminology (LAST) as those leading to low-grade squamous intraepithelial lesions (LSIL) or high-grade squamous intraepithelial lesions (HSIL) [6]. About 75% of women infected with high-risk HPV display normal cytological features and present no lesions [4]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
