Background: 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 transcription factors has been observed in several types of cancer. To date, however, no reports exist on the expression of HOXB2 and HOXB13 proteins during neoplastic progression in CeCa and its correlation with HPV infection. Materials and Methods: Expression of HOXB2 and HOXB13 proteins was assessed in tissue microarrays from normal cervical epithelium, cervical intraepithelial neoplasias grade 1-3, and CeCa. HPV was detected by PCR and sequencing. Expression of HOX-positive cells was determined in each diagnostic group. Results: Percentage of HOXB2-and HOXB13-positive cells gradually increased from means of 10.9% and 16.7%, respectively, in samples from healthy women, to 75.2% and 88.6% in those from CeCa patients. Frequency of HPV infection also increased from 13% in healthy tissue samples to 92.3% in CeCa. Both HOXB2 and HOXB13 proteins were preferentially expressed in HPV+ samples. Conclusions: The present study represents the first report on the expression of both HOXB2 and HOXB13 proteins through cervix tumorigenesis, providing evidence that increased expression of such proteins is a common event during progression to CeCa.
Cervical cancer (CC) is the second most common cancer in Mexican women. Human papillomavirus (HPV) infection is necessary but not sufficient for CC development. Furthermore, genetic factors as polymorphisms could be important susceptibility factors. Controversial results regarding TP53 polymorphisms specifically in codon 72 of CC have been reported. In the present work, the exon 4 sequence of TP53 gene in CC and healthy Mexican-mestizo women were analyzed. A group of 111 women with CC and 126 healthy women (control) were included. Peripheral blood cells for polymorphism analysis and cervical scrape for HPV detection were used. PCR of exon 4 of TP53 were subjected to denaturing high-performance liquid chromatography (DHPLC) analysis and sequencing. HPV detection was subjected to PCR and sequencing. The statistical analysis was carried out using the Arlequin software. Codon 72 Arg/Arg was the most common SNP detected, and Hardy-Weinberg analysis showed equilibrium in control and CC samples (P>0.05). Wild type sequence of TP53 exon 4 was detected in 66 and 57% in control and CC samples, respectively. For codon 72 Arg/Arg, differences between control and CC women were found (P=0.043). An association between HPV 16/18 infection and 72 Arg/Arg in woman with CC was found (P=0.026). Haplotype GC (codon 36 and 72) was statistically significantly associated with CC (P=0.011). HPV 16 was the most common viral type. Codon 72 Arg/Arg is the most common polymorphism in the Mexican population and could be associated to HPV 16 and/or HPV 18 infection in CC.
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