GYNECOLOGIC ONCOLOGY 12, S42-S55 (1981) Detection of Nucleic Acid Sequences in Cervical Tumors JAMES K. MCDOUGALL,* DENISE A. GALLOWAY,* CHRISTOPHER CRUM,~ RICHARD LEVINE,$ RALPH RICHART,t AND CECILIA M. FENoGLIot *Fred Hutchinson Cancer Research Center, 1124 Columbia Street, Seattle, Washington 98104; and Departments of tPathology, and SObstetrics and Gynecology, Columbia University, College of Physicians and Surgeons, 168th Street and Broadway, New York, New York 10032 Presented at the Conference on Early Cervical Neoplasia, March 23-25, 1981 Our results suggest that HSV RNA is present in abnormal cells of a significant proportion of cervical tissue specimens containing intraepithelial neoplasia and that it is only rarely detected in sections of normal cervical epithelium. A proliferation of atypical basal-type cells and their continued persistence through the more mature upper layers is the first indication of dysplasia and CIN in cervical epithelium, and it is in these proliferating cells that evidence of HSV RNA can be found. The results of localizing an HSV-2 antigen (ICSP 11-12) closely parallel the in situ hybridization results. About 30% of patients with dysplasia (CIN I and II) have detectable antigen. It is interesting to note that the incidence of detectable antigen decreased to 12% in patients with carcinoma in situ, but was de- monstrable in 20% of patients who had microinvasive or invasive squamous cell lesions. INTRODUCTION Herpesviruses are widespread in humans, primates, and other animals and are the causative agents of diseases ranging from relatively mild skin eruptions to severe and frequently fatal encephalitis. Some members of the group Herpeto- viridae are convincingly associated with naturally occurring cancers, e.g., Ma- rek’s disease virus (MDV) in poultry, Lucke carcinoma in the frog, and Ep- stein-Barr virus (EBV) in Burkitt’s lymphoma and in nasopharyngeal carcinoma in man. Herpes simplex virus type 1 (HSV-l), HSV-2, and cytomegalovirus (CMV) have been proposed as having etiologic roles in other cancers in humans, e.g., uterine cervical carcinoma and other urogenital tumors. Herpesviruses are large DNA-containing viruses with a virion diameter of 100 nm, although en- veloped virions may be up to 200 nm in diameter. The molecular weight of nucleic acid ranges from 92 to 150 x lo6 daltons. Apart from EBV, the herpesviruses indigenous to man (HSV-1, HSV-2, CMV, and herpes zoster (HZV)) will replicate in and undergo productive infection in most in vitro cul- tivated mammalian cells. Virion production is accompanied by metabolic and structural changes in the host cell which eventually lead to cell death. There are, however, two examples in which retention and/or replication of the entire replicative machinery of the virus is compatible with cell survival. EBV can persist in peripheral lymphoid cells which when placed in in vitro culture may either themselves establish cell lines or by undergoing productive infection release S42 0090-8258/81/05OS42-14$01.00/O Copyright Q 1981 by Academic Press, Inc. All rights of reproduction in any form reserved.