Co-expression of HSV2 and Chlamydia trachomatis in HPV-positive cervical cancer and cervical intraepithelial neoplasia lesions is associated with aberrations in key intracellular pathways.
OBJECTIVE
Oncogenic human papillomaviruses (HPVs) are the etiological agents of cervical cancer. Different cofactors might be needed for malignant transformation, but they still remain elusive.


METHODS
To delineate the role of Chlamydia trachomatis (CT) and herpes simplex virus type 2 (HSV2) in HPV-positive cervical intraepithelial neoplasia (CIN) lesions and cervical carcinoma a series of 149 cervical cancer and CIN biopsies were analyzed for CT and HSV2 DNA by PCR, and HPV genotyped by InnoLipa. Monitoring of aberrations in key intracellular pathways due to CT/HSV2 and HPV co-expression were analyzed with 13 biomarkers.


RESULTS
Of the 149 samples tested, 136 were HPV DNA positive; 32/136 contained also CT DNA and 29 HSV2 DNA. Detection of CT was significantly (p = 0.0001) related to multiple-type HPV infections, while HSV2 was of borderline significance (p = 0.053). Of the 13 biomarkers tested, cytoplasmic and nuclear NF-kappaB and VEGF-C were significantly increased in CT+/HPV+ lesions; p = 0.023, p = 0.045, and p = 0.020 as well as survivin, p = 0.026. Survivin was the only marker that was overexpressed also in HSV2+/HPV+ lesions, p = 0.027.


CONCLUSIONS
CT infection favors the entry and persistence of multiple HR-HPV types, which leads to viral integration, inhibition of apoptosis, overexpression of E6/E7 oncogenes and cell transformation.
Paba
Pierpaolo
P
Laboratory of Clinical Microbiology and Virology, University Hospital Tor Vergata, Rome, Italy.
Bonifacio
Daniela
D
Di Bonito
Luigi
L
Ombres
Domenico
D
Favalli
Cartesio
C
Syrjänen
Kari
K
Ciotti
Marco
M
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002692:Chlamydia trachomatis / Q000235:genetics / Q000302:isolation & purification*; D004269:DNA, Bacterial / Q000032:analysis; D004279:DNA, Viral / Q000032:analysis; D005260:Female; D020869:Gene Expression Profiling; D018258:Herpesvirus 2, Human / Q000235:genetics / Q000302:isolation & purification*; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins; D008869:Microtubule-Associated Proteins / Q000096:biosynthesis / Q000235:genetics; D008875:Middle Aged; D016328:NF-kappa B / Q000096:biosynthesis / Q000235:genetics; D009363:Neoplasm Proteins / Q000096:biosynthesis / Q000235:genetics; D027383:Papillomaviridae / Q000145:classification / Q000235:genetics / Q000302:isolation & purification*; D030361:Papillomavirus Infections / Q000150:complications*; D016133:Polymerase Chain Reaction; D000077022:Survivin; D042582:Vascular Endothelial Growth Factor C / Q000096:biosynthesis / Q000235:genetics; D002578:Uterine Cervical Dysplasia / Q000382:microbiology* / Q000821:virology*
C107489:BIRC5 protein, human; D004269:DNA, Bacterial; D004279:DNA, Viral; D051034:Inhibitor of Apoptosis Proteins; D008869:Microtubule-Associated Proteins; D016328:NF-kappa B; D009363:Neoplasm Proteins; D000077022:Survivin; D042582:Vascular Endothelial Growth Factor C