Increased Expression of HOXB2 and HOXB13 Proteins is Associated with HPV Infection and Cervical Cancer Progression

Abstract

<b>Background:</b> Cervical cancer (CeCa) is the second most common cancer in women in developing countries,and human papilloma virus (HPV) is the primary etiological factor. Aberrant expression of HOX transcriptionfactors has been observed in several types of cancer. To date, however, no reports exist on the expression ofHOXB2 and HOXB13 proteins during neoplastic progression in CeCa and its correlation with HPV infection.Materials and <br/><b>Methods</b>: Expression of HOXB2 and HOXB13 proteins was assessed in tissue microarrays fromnormal cervical epithelium, cervical intraepithelial neoplasias grade 1-3, and CeCa. HPV was detected by PCRand sequencing. Expression of HOX-positive cells was determined in each diagnostic group. <br/><b>Results</b>: Percentageof HOXB2- and HOXB13-positive cells gradually increased from means of 10.9% and 16.7%, respectively, insamples from healthy women, to 75.2% and 88.6% in those from CeCa patients. Frequency of HPV infectionalso increased from 13% in healthy tissue samples to 92.3% in CeCa. Both HOXB2 and HOXB13 proteinswere preferentially expressed in HPV+ samples. <br/><b>Conclusions</b>: The present study represents the first report onthe expression of both HOXB2 and HOXB13 proteins through cervix tumorigenesis, providing evidence thatincreased expression of such proteins is a common event during progression to CeCa.