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Background Herpesvirus 8 (HHV-8) oncoprotein K1 is linked to lymphoproliferation and suppression of apoptosis mediated by the Fas death receptor. Expression of K1 in transgenic mice induces accumulation of lymphoid tissue cells and lymphoma. Methods To examine how K1 and Fas interact to suppress apoptosis, K1--Fas binding was studied in human embryonic kidney (HEK) and lymphoma (BJAB) cells that expressed wild-type K1 or a K1 lg domain deletion mutant and were treated with Fas ligand (FasL) or an agonistic Fas antibody, using immunoprecipitation and Western blot analysis. Cleavage of caspase-3 and apoptosis was compared in liver samples from mice that were transfected with empty vector vs with plasmids expressing wild-type K1 or a K1 lg deletion mutant and treated with agonistic Fas antibody for 7 hours. These studies used immunohistochemical staining and terminal deoxynucleotidyl transferase--mediated dUTP nick end labeling assay. All statistical tests were two-sided. Results Immunoprecipitation and Western blot analysis of transfected HEK and B JAB cells revealed that wild-type K1 but not lg-deleted K1 binds to Fas and prevents Fas activation by FasL or by an agonistic Fas antibody. More mice that were transfected with wild-type K1 (7 of 10) than mice transfected with empty vector (3 of 13) or the K1 lg deletion mutant (0 of 6) survived treatment with the agonistic Fas antibody. Compared with vectortransfected mice, livers of wild-type K1-transfected mice contained fewer cells in which caspase-3 was cleaved (87.6% vs 58.0%, difference = 29.6%, 95% confidence interval [CI] = 19.2% to 40.0%; P = .003) and fewer apoptotic cells (83.7% vs 34.2%, difference = 49.5%, 95% CI = 39.8% to 59.2%; P = .003). Conclusions K1 blocks Fas signaling by directly binding to Fas through the lg-like domain of K1 and preventing binding of FasL. The relative resistance of cancer cells to Fas-mediated apoptosis may be due to the inhibition of Fas by lg domain--containing proteins.

Some human papillomavirus infections of the uterine cervix may go away spontaneously, especially if the virus is one of the types that does not necessarily cause cervical cancer. Researchers studied 1,006 women who were referred for a biopsy because they had an abnormal Pap smear. In many of the women, the biopsy done between two to four months later showed a normal cervix. This means the infection cleared spontaneously.

Byline: Ervin Adam, Zuzana Berkova, Zuzana Daxnerova, Joseph Icenogle, William C. Reeves, Raymond H. Kaufman Keywords: Cervical intraepithelial neoplasia; human papillomavirus; polymerase chain reaction; risk factors; screening Abstract: Objective: This study was undertaken to assess the association between detection of high-risk types of human papillomavirus and various demographic and behavioral characteristics and to further relate this association to cervical histopathologic findings. Study Design: A total of 1007 patients with a Papanicolaou test result reported as high-grade squamous intraepithelial lesion or with 2 results reported as atypical squamous cells of undetermined significance or low-grade squamous intraepithelial lesion were referred from city and county clinics to a colposcopic clinic. All women had a cervical smear obtained, underwent colposcopically directed biopsy and endocervical curettage, and had a specimen taken for human papillomavirus deoxyribonucleic acid detection by polymerase chain reaction. Demographic information was obtained from each patient. Results: Human papillomavirus deoxyribonucleic acid was identified in 655 (66%) of the specimens. High-risk human papillomavirus types (16, 18, 31, 33, and 35) were detected in 463 (70.7%) of these specimens. The prevalence of evidence of human papillomavirus (koilocytosis) and grade 1 cervical intraepithelial neoplasia in the biopsy specimen decreased significantly with age, whereas the prevalence of grade 2 or 3 cervical intraepithelial neoplasia in the biopsy specimen increased with age. There was a significant age-dependent decreasing trend in detection of high-risk human papillomavirus deoxyribonucleic acid among women who had human papillomavirus-associated changes, grade 1 cervical intraepithelial neoplasia, and grade 2 or 3 cervical intraepithelial neoplasia in the biopsy specimen. The prevalences of high-risk human papillomavirus among patients with grade 1 cervical intraepithelial neoplasia and grade 2 or 3 cervical intraepithelial neoplasia were similar, and both were significantly higher than among women with no evidence of cervical intraepithelial neoplasia or koilocytosis in the biopsy specimen. Risk factors associated with grade 2 or 3 cervical intraepithelial neoplasia were different from those associated with human papillomavirus-associated changes and with grade 1 cervical intraepithelial neoplasia. Conclusion: The detection of high-risk human papillomavirus was age-dependent for all histologic categories. Patients with grade 2 or 3 cervical intraepithelial neoplasia had a prevalence of high-risk human papillomavirus that was similar to that among women with grade 1 cervical intraepithelial neoplasia but significantly higher than that among women whose biopsy specimens appeared normal or demonstrated only the presence of human papillomavirus-induced changes (koilocytosis). This suggests that separation of human papillomavirus-associated changes only from grade 1 cervical intraepithelial neoplasia may be of significance in tissue diagnosis. (Am J Obstet Gynecol 2000;182:257-64.) Author Affiliation: Houston, Texas, and Atlanta, Georgia From the Division of Molecular Virology.sup.a and the Department of Obstetrics and Gynecology,.sup.b Baylor College of Medicine, and the Centers for Disease Control and Prevention..sup.c Article History: Received 25 January 1999; Revised 12 July 1999; Accepted 23 September 1999 Article Note: (footnote) [star] Supported by contract 200-92-0537 of the Centers for Disease Control and Prevention., [star][star] Reprint requests: Raymond H. Kaufman, MD, Baylor College of Medicine, Department of Obstetrics and Gynecology, 6550 Fannin, Suite 701, Houston, TX 77030.

Women with cervical human papillomavirus (HPV) infections who have only mild changes on a Pap smear probably do not have cervical cancer or its precursor, a condition called cervical intraepithelial neoplasia (CIN). In a study of 1,007 women, those with mild changes were less likely to be infected with HPV types that have been linked to cervical cancer. Women with CIN were more likely to have these viral types.

The polymerase chain reaction appears to be effective in detecting human papillomavirus type 16 in cervical tissue samples from women with an abnormal Pap smear. Researchers used this screening method on 1,007 women with an abnormal Pap smear. A total of 553 had high-grade cervical intraepithelial neoplasia, which is a risk factor for cervical cancer. Human papillomavirus type 16, which is also a risk factor for cervical cancer, was found in 60% of these women, but only in 33% of the women without cervical intraepithelial neoplasia.

Byline: Ervin Adam, Raymond H. Kaufman, Zuzana Berkova, Joseph Icenogle, William C. Reeves Keywords: Human papillomavirus; polymerase chain reaction; cervical intraepithelial neoplasia; screening Abstract: OBJECTIVE: Our purpose was to assess the usefulness of the polymerase chain reaction assay for detection of human papillomavirus infection for prognostic value in the triage strategies for high-grade (grade 2 or 3) cervical intraepithelial neoplasia in women referred for colposcopy after abnormal Papanicolaou smears. STUDY DESIGN: A total of 1007 women referred to a colposcopic clinic providing care for an indigent population were studied. Four hundred fifty-four women were referred after two Papanicolaou smears reported as atypical squamous cells of undetermined significance or low grade-squamous cervical intraepithelial lesion, and 553 were referred after a single smear reported as high-grade squamous intraepithelial lesion. All women had a cervical smear, colposcopy-directed biopsy, and endocervical curettage performed. A sample for human papillomavirus deoxyribonucleic acid detection by polymerase chain reaction was obtained. RESULTS: High-risk human papillomavirus types were detected in 463 (46%) of 1007 women studied. There was a significant increase of the frequency of high-risk human papillomavirus by the increasing severity of biopsy findings ranging from 32.7% in women without cervical intraepithelial neoplasia on biopsy to 60% in women having grade 2 or 3 on the biopsy specimen. Women having a negative Papanicolaou smear found to have high-risk human papillomavirus deoxyribonucleic acid at the time of colposcopy had a significantly higher rate of grade 2 or 3 cervical intraepithelial neoplasia on the biopsy specimen than did women without high-risk human papillomavirus. There was no such difference observed in women with a cytologic finding of low- or high-grade squamous intraepithelial lesions at the time of colposcopy. The polymerase chain reaction assay appears to be more sensitive than the commercial human papillomavirus profile test. The positive predictive value for grade 2 or 3 cervical intraepithelial neoplasia of both tests was similar (21.7% and 22.8%, respectively). CONCLUSION: The human papillomavirus is associated with high-grade cervical intraepithelial neoplasia, but the screening for human papillomavirus deoxyribonucleic acid does not have prognostic value in women reported as having atypical squamous cells of undetermined significance or low-grade squamous intraepithelial lesions on two precolposcopy Papanicolaou smears. (Am J Obstet Gynecol 1998;178:1235-44.) Author Affiliation: Houston, Texas, and Atlanta, Georgia Article Note: (footnote) [star] From the Division of Molecular Virologya and the Department of Obstetrics and Gynecology,b Baylor College of Medicine, and the Centers for Disease Control and Prevention.c , [star][star] Supported by contract No. 200-92-0537, Centers for Disease Control and Prevention, Atlanta, Georgia., a Reprint requests: Raymond H. Kaufman, MD, Baylor College of Medicine, Department of Obstetrics and Gynecology, 6550 Fannin, Suite 701, Houston, TX 77030., aa 6/6/89840