Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2024 Nov 26;12(12):2699.
doi: 10.3390/biomedicines12122699.

Serum Antibodies Against the E5 Oncoprotein from Human Papillomavirus Type 16 Are Inversely Associated with the Infection and the Degree of Cervical Lesions

Azucena Salazar-Piña  1 , Minerva Maldonado-Gama  2 , Ana M Gonzalez-Jaimes  3 , Aurelio Cruz-Valdez  4 , Eduardo Ortiz-Panozo  4 , Fernando Esquivel-Guadarrama  5 , Lourdes Gutierrez-Xicotencatl  2
Affiliations

Serum Antibodies Against the E5 Oncoprotein from Human Papillomavirus Type 16 Are Inversely Associated with the Infection and the Degree of Cervical Lesions

Azucena Salazar-Piña et al. Biomedicines. .

Abstract

Background: The humoral immune response against human papillomavirus (HPV) has been suggested as a source of biomarkers for the early detection of cervical cancer (CC). Therefore, we aimed to characterize the antibody response against HPV16 E5 in the natural history of cervical cancer and to determine its usefulness as a biomarker of HPV-associated cervical lesions.

Methods: This study was conducted at the Cuautla General Hospital, Morelos, Mexico, with women (18 to 64 years) who agreed to participate. Samples were obtained from 335 women with cervical lesions and 150 women with negative Papanicolaou tests. HPV genotyping was performed by PCR and pyrosequencing, and anti-E5 antibodies were detected by slot blot.

Results: The overall anti-E5 antibodies prevalence in the study was 17.9%, with the higher prevalence observed in the no lesion (NL, 49.4%) group, and with a downward trend according to the degree of the cervical lesion, from cervical intraepithelial neoplasia-1 (CIN1, 32.2%) to CIN2 (11.5%) and CIN3/CC (6.9%). The logistic regression model showed negative associations of anti-E5 antibodies with CIN1 (OR = 0.38), CIN2 (OR = 0.42), and CIN3/CC (OR = 0.32) groups, being statistically significant. Contrast analysis showed an inverse relationship between anti-E5 antibodies with HPV DNA and the CIN1 (OR = 0.35), CIN2 (OR = 0.39), and CIN3/CC (OR = 0.31) groups.

Conclusions: These results suggest that anti-E5 antibodies could be associated with clearance of infection in women without lesions and with CIN1 lesions since an inverse relationship was observed between the presence of HPV DNA and anti-E5 antibodies. In contrast, with progression from CIN2/CIN3 to CC, the relationship was reversed, as the anti-E5 antibodies disappeared, and the frequency of the viral genome increased.

Keywords: HPV16; anti-E5 antibodies; cervical cancer; cervical intraepithelial neoplasia; serology.

PubMed Disclaimer

Conflict of interest statement

The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.

Figures

Figure 1
Figure 1
Flow diagram of the female population that participated in the study. CIN, cervical intraepithelial neoplasia grade 1, 2, or 3; CC, cervical cancer.
Figure 2
Figure 2
Anti-E5 antibody levels in women with different cervical lesions and CC. The median and interquartile range for each of the different cervical lesions are shown in the dispersion graph. The dashed line represents the cut-off point (5 AU/mL) as calculated for antibodies against E5 and described in Materials and Methods Section. The data were analyzed by the difference of medians using Kruskal–Wallis and Dunn testing, and statistical significances are shown as * p < 0.05.
Figure 3
Figure 3
Frequency of anti-E5 antibodies and HPV DNA in women with different cervical lesions and CC. The frequency of women that were positive for anti-E5 antibodies and/or HPV DNA was plotted in a graph by the degree of the cervical lesion and analyzed for possible interactions. Anti-E5 antibodies (▪); HPV DNA (●).
See this image and copyright information in PMC

References

    1. zur Hausen H. Papillomaviruses in the causation of human cancers—A brief historical account. Virology. 2009;384:260–265. doi: 10.1016/j.virol.2008.11.046. - DOI - PubMed
    1. de Sanjose S., Serrano B., Tous S., Alejo M., Lloveras B., Quiros B., Clavero O., Vidal A., Ferrandiz-Pulido C., Pavon M.A., et al. Burden of Human Papillomavirus (HPV)-Related Cancers Attributable to HPVs 6/11/16/18/31/33/45/52 and 58. JNCI Cancer Spectr. 2018;2:pky045. doi: 10.1093/jncics/pky045. - DOI - PMC - PubMed
    1. Serrano B., Brotons M., Bosch F.X., Bruni L. Epidemiology and burden of HPV-related disease. Best. Pract. Res. Clin. Obstet. Gynaecol. 2018;47:14–26. doi: 10.1016/j.bpobgyn.2017.08.006. - DOI - PubMed
    1. Aguilar-Lemarroy A., Vallejo-Ruiz V., Cortes-Gutierrez E.I., Salgado-Bernabe M.E., Ramos-Gonzalez N.P., Ortega-Cervantes L., Arias-Flores R., Medina-Diaz I.M., Hernandez-Garza F., Santos-Lopez G., et al. Human papillomavirus infections in Mexican women with normal cytology, precancerous lesions, and cervical cancer: Type-specific prevalence and HPV coinfections. J. Med. Virol. 2015;87:871–884. doi: 10.1002/jmv.24099. - DOI - PubMed
    1. Sung H., Ferlay J., Siegel R.L., Laversanne M., Soerjomataram I., Jemal A., Bray F. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J. Clin. 2021;71:209–249. doi: 10.3322/caac.21660. - DOI - PubMed

LinkOut - more resources