Does Epstein-Barr virus play a role in lymphoepithelioma-like carcinoma of the uterine cervix?

The role of Epstein-Barr viruses (EBVs) in lymphoepithelioma-like carcinoma (LELC) of the uterine cervix is controversial. We aimed to investigate the existence of EBV and human papillomavirus (HPV) in LELC of the cervix. Nine patients of LELC of the cervix, treated at Chang Gung Memorial Hospital between 1996 and 2000, with complete clinicopathologic findings and follow-up data were studied. Twenty-five patients with squamous cell carcinoma were recruited as controls. The EBV genome was measured by real-time quantitative polymerase chain reaction (PCR) and EBV-encoded RNA in situ hybridization from formalin-fixed, paraffin-embedded tissues. HPV genotyping was carried out by SPF1/GP6+ PCR and hybridization with a GeneChip. Type-specific E6 PCR of the 18 most commonly found HPV genotypes in Taiwan was also performed. HPV-16 was found in 3 cases, HPV-18, HPV-31, and HPV-35, and HPV-58 in 1 case each. One case showed positive for both HPV-16 and HPV-58. Low copy number of EBV DNA was found in 9 cases of LELC (1-14.7 copies/microg) and 7 cases of squamous cell carcinoma (3.8-1586 copies/microg) using real-time quantitative PCR Bam H1 W fragment probe, but EBV-encoded RNA-in situ hybridization was negative in tumor cells. Therefore, positive rates for EBV and HPV were 0% and 88.9% (8/9) in LELC of the cervix, respectively. All patients with LELC of the cervix had no evidence of disease for more than 5 years from diagnoses. Our results suggest that EBV is not involved in the carcinogenesis of so-called LELC of the cervix but the EBV sequences might exist in a florid inflammatory stromal component.