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Published in: BMC Cancer 1/2001

Open Access 01-12-2001 | Research article

Human papillomavirus DNA in plasma of patients with cervical cancer

Authors: Wichai Pornthanakasem, Kanjana Shotelersuk, Wichai Termrungruanglert, Narin Voravud, Somchai Niruthisard, Apiwat Mutirangura

Published in: BMC Cancer | Issue 1/2001

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Abstract

Background

Human papillomavirus (HPV) is a crucial etiological factor for cervical cancer (CC) development. From a diagnostic view-point, the consistent presence of HPV in CC allows the viral DNA to be used as a genetic marker. The aims of this study were to evaluate the presence, physical status and clinical significant of HPV DNA in circulation of CC patients.

Results

Whereas 6 out of 50 (12%) HPV positive CC patients revealed plasma HPV DNA, it was detected in none of 20 normal controls or 13 HPV negative CC cases. The plasma DNA exhibited an HPV type identical to the HPV in the primary tumors and the DNA from both sources was integrated into host genome. Interestingly, several findings suggested an association between plasma HPV DNA and metastasis. First, three of the HPV DNA positive cases were CC patients with clinical stage IVB or recurrence with distance metastases (P = 0.001, RR = 15.67). Second, the amount of plasma HPV DNA from metastatic patients to be three times more than three other patients without metastases. Finally, the later cases had tendency to develop recurrence distant metastases within one year after complete treatment when compared with other HPV associated CC patients with the same stage but without the present of plasma HPV DNA.

Conclusions

The plasma HPV DNA originated from the CC, was associated with metastasis and could be used as a marker representing the circulating free CC DNA.
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Literature
1.
go back to reference Cannistra SA, Niloff JM: Cancer of the uterine cervix. N Engl J Med. 1996, 334: 1030-1038. 10.1056/NEJM199604183341606.CrossRefPubMed Cannistra SA, Niloff JM: Cancer of the uterine cervix. N Engl J Med. 1996, 334: 1030-1038. 10.1056/NEJM199604183341606.CrossRefPubMed
3.
go back to reference Bosch FX, Manos MM, Munoz N, Sherman M, Jansen AM, Peto J, Schiffman MH, Moreno V, Kurman R, Shah KV: Prevalence of human papillomavirus in cervical cancer: a worldwide perspective International biological study on cervical cancer (IBSCC) Study Group. J Natl Cancer Inst. 1995, 87: 796-802. 10.1093/jnci/87.11.796.CrossRefPubMed Bosch FX, Manos MM, Munoz N, Sherman M, Jansen AM, Peto J, Schiffman MH, Moreno V, Kurman R, Shah KV: Prevalence of human papillomavirus in cervical cancer: a worldwide perspective International biological study on cervical cancer (IBSCC) Study Group. J Natl Cancer Inst. 1995, 87: 796-802. 10.1093/jnci/87.11.796.CrossRefPubMed
4.
go back to reference Schiffman MH, Bauer HM, Hoover RN, Glass AG, Cadell DM, Rush BB, Scott DR, Sherman ME, Kurman RJ, Wacholder S, Stanton CK, Manos MM: Epidemiologic evidence showing that human papillomavirus infection causes most cervical intraepithelial neoplasia. J Natl Cancer Inst. 1993, 85: 958-964. 10.1093/jnci/85.12.958.CrossRefPubMed Schiffman MH, Bauer HM, Hoover RN, Glass AG, Cadell DM, Rush BB, Scott DR, Sherman ME, Kurman RJ, Wacholder S, Stanton CK, Manos MM: Epidemiologic evidence showing that human papillomavirus infection causes most cervical intraepithelial neoplasia. J Natl Cancer Inst. 1993, 85: 958-964. 10.1093/jnci/85.12.958.CrossRefPubMed
5.
go back to reference Kubbutant MHG, Vousden KH: Role of E6 and E7 oncoproteins in HPV-induced anogenital malignancies. Semin Virol. 1996, 7: 295-304. 10.1006/smvy.1996.0037.CrossRef Kubbutant MHG, Vousden KH: Role of E6 and E7 oncoproteins in HPV-induced anogenital malignancies. Semin Virol. 1996, 7: 295-304. 10.1006/smvy.1996.0037.CrossRef
6.
go back to reference Baker CC, Phelps WC, Lindgren V, Braun MJ, Gonda MA, Howley PM: Structural and transcriptional analysis of human papillomavirus type 16 sequences in cervical carcinoma cell lines. J Virol. 1987, 61: 962-971.PubMedPubMedCentral Baker CC, Phelps WC, Lindgren V, Braun MJ, Gonda MA, Howley PM: Structural and transcriptional analysis of human papillomavirus type 16 sequences in cervical carcinoma cell lines. J Virol. 1987, 61: 962-971.PubMedPubMedCentral
7.
go back to reference Park JS, Hwang ES, Park SN, Ahn HK, Um SJ, Kim CJ, Kim SJ, Namkoong SE: Physical status and expression of HPV genes in cervical cancers. Gynecol Oncol. 1997, 65: 121-129. 10.1006/gyno.1996.4596.CrossRefPubMed Park JS, Hwang ES, Park SN, Ahn HK, Um SJ, Kim CJ, Kim SJ, Namkoong SE: Physical status and expression of HPV genes in cervical cancers. Gynecol Oncol. 1997, 65: 121-129. 10.1006/gyno.1996.4596.CrossRefPubMed
8.
go back to reference Cuzick J: Human papillomavirus testing for primary cervical cancer screening. JAMA. 2000, 283: 108-109. 10.1001/jama.283.1.108.CrossRefPubMed Cuzick J: Human papillomavirus testing for primary cervical cancer screening. JAMA. 2000, 283: 108-109. 10.1001/jama.283.1.108.CrossRefPubMed
9.
go back to reference Sidransky D: Circulating DNA: What we know and what we need to learn. Ann N Y Acad Sci. 2000, 906: 1-4.CrossRefPubMed Sidransky D: Circulating DNA: What we know and what we need to learn. Ann N Y Acad Sci. 2000, 906: 1-4.CrossRefPubMed
10.
go back to reference Stroun M, Maurice P, Vasioukhin V, Lyautey J, Lederrey C, Lefort F, Rossier A, Chen XQ, Anker P: The origin and mechanism of circulating DNA. Ann N Y Acad Sci. 2000, 906: 161-168.CrossRefPubMed Stroun M, Maurice P, Vasioukhin V, Lyautey J, Lederrey C, Lefort F, Rossier A, Chen XQ, Anker P: The origin and mechanism of circulating DNA. Ann N Y Acad Sci. 2000, 906: 161-168.CrossRefPubMed
11.
go back to reference Jen J, Wu L, Sidransky D: An overview on the isolation and analysis of circulating tumor DNA in plasma and serum. Ann N Y Acad Sci. 2000, 906: 8-12.CrossRefPubMed Jen J, Wu L, Sidransky D: An overview on the isolation and analysis of circulating tumor DNA in plasma and serum. Ann N Y Acad Sci. 2000, 906: 8-12.CrossRefPubMed
12.
go back to reference Anker P, Mulcahy H, Chen XQ, Stroun M: Detection of circulating tumour DNA in the blood (plasma/serum) of cancer patients. Cancer Metastasis Rev. 1999, 18: 65-73. 10.1023/A:1006260319913.CrossRefPubMed Anker P, Mulcahy H, Chen XQ, Stroun M: Detection of circulating tumour DNA in the blood (plasma/serum) of cancer patients. Cancer Metastasis Rev. 1999, 18: 65-73. 10.1023/A:1006260319913.CrossRefPubMed
13.
go back to reference Mutirangura A, Pornthanakasem W, Theamboonlers A, Sriuranpong V, Lertsanguansinchi P, Yenrudi S, Voravud N, Supiyaphun P, Poovorawan Y: Epstein-Barr viral DNA in serum of patients with nasopharyngeal carcinoma. Clin Cancer Res. 1998, 4: 665-669.PubMed Mutirangura A, Pornthanakasem W, Theamboonlers A, Sriuranpong V, Lertsanguansinchi P, Yenrudi S, Voravud N, Supiyaphun P, Poovorawan Y: Epstein-Barr viral DNA in serum of patients with nasopharyngeal carcinoma. Clin Cancer Res. 1998, 4: 665-669.PubMed
14.
go back to reference Tangkijvanich P, Hirsch P, Theamboonlers A, Nuchprayoon I, Poovorawan Y: Association of hepatitis viruses with hepatocellular carcinoma in Thailand. J Gastroenterol. 1999, 34: 227-233. 10.1007/s005350050248.CrossRefPubMed Tangkijvanich P, Hirsch P, Theamboonlers A, Nuchprayoon I, Poovorawan Y: Association of hepatitis viruses with hepatocellular carcinoma in Thailand. J Gastroenterol. 1999, 34: 227-233. 10.1007/s005350050248.CrossRefPubMed
15.
go back to reference Shotelersuk K, Khorprasert C, Sakdikul S, Pornthanakasem W, Voravud N, Mutirangura A: Epstein-Barr virus DNA in serum/plasma as a tumor marker for nasopharyngeal cancer. Clin Cancer Res. 2000, 6: 1046-1051.PubMed Shotelersuk K, Khorprasert C, Sakdikul S, Pornthanakasem W, Voravud N, Mutirangura A: Epstein-Barr virus DNA in serum/plasma as a tumor marker for nasopharyngeal cancer. Clin Cancer Res. 2000, 6: 1046-1051.PubMed
16.
go back to reference Lo YM, Chan LY, Lo KW, Leung SF, Zhang J, Chan AT, Lee JC, Hjelm NM, Johnson PJ, Huang DP: Quantitative analysis of cell-free Epstein-Barr virus DNA in plasma of patients with nasopharyngeal carcinoma. Cancer Res. 1999, 59: 1188-1191.PubMed Lo YM, Chan LY, Lo KW, Leung SF, Zhang J, Chan AT, Lee JC, Hjelm NM, Johnson PJ, Huang DP: Quantitative analysis of cell-free Epstein-Barr virus DNA in plasma of patients with nasopharyngeal carcinoma. Cancer Res. 1999, 59: 1188-1191.PubMed
17.
go back to reference Resnick RM, Cornelissen MT, Wright DK, Eichinger GH, Fox HS, ter Schegget J, Manos MM: Detection and typing of human papillomavirus in archival cervical cancer specimens by DNA amplification with consensus primers. J Natl Cancer Inst. 1990, 82: 1477-1484. 10.1093/jnci/82.18.1477.CrossRefPubMed Resnick RM, Cornelissen MT, Wright DK, Eichinger GH, Fox HS, ter Schegget J, Manos MM: Detection and typing of human papillomavirus in archival cervical cancer specimens by DNA amplification with consensus primers. J Natl Cancer Inst. 1990, 82: 1477-1484. 10.1093/jnci/82.18.1477.CrossRefPubMed
18.
go back to reference Cui KH, Warnes GM, Jeffrey R, Matthews CD: Sex determination of preimplantation embryos by human testis-determining-gene amplification. Lancet. 1994, 343: 79-82. 10.1016/S0140-6736(94)90815-X.CrossRefPubMed Cui KH, Warnes GM, Jeffrey R, Matthews CD: Sex determination of preimplantation embryos by human testis-determining-gene amplification. Lancet. 1994, 343: 79-82. 10.1016/S0140-6736(94)90815-X.CrossRefPubMed
20.
go back to reference Martel-Renoir D, Grunewald V, Touitou R, Schwaab G, Joab I: Qualitative analysis of the expression of Epstein-Barr virus lytic genes in nasopharyngeal carcinoma biopsies. J Gen Virol. 1995, 76: 1401-8.CrossRefPubMed Martel-Renoir D, Grunewald V, Touitou R, Schwaab G, Joab I: Qualitative analysis of the expression of Epstein-Barr virus lytic genes in nasopharyngeal carcinoma biopsies. J Gen Virol. 1995, 76: 1401-8.CrossRefPubMed
21.
go back to reference Joab I, Nicolas JC, Schwaab G, de-Thoe G, Clausse B, Perricaudet M, Zeng Y: Detection of anti-Epstein-Barr-virus transactivator (ZEBRA) antibodies in sera from patients with nasopharyngeal carcinoma. Int J Cancer. 1991, 48: 647-649.CrossRefPubMed Joab I, Nicolas JC, Schwaab G, de-Thoe G, Clausse B, Perricaudet M, Zeng Y: Detection of anti-Epstein-Barr-virus transactivator (ZEBRA) antibodies in sera from patients with nasopharyngeal carcinoma. Int J Cancer. 1991, 48: 647-649.CrossRefPubMed
22.
go back to reference Sanchez-Cespedes M, Esteller M, Wu L, Nawroz-Danish H, Yoo GH, Koch WM, Jen J, Herman JG, Sidransky D: Gene promoter hypermethylation in tumors and serum of head and neck cancer patients. Cancer Res. 2000, 60: 892-5.PubMed Sanchez-Cespedes M, Esteller M, Wu L, Nawroz-Danish H, Yoo GH, Koch WM, Jen J, Herman JG, Sidransky D: Gene promoter hypermethylation in tumors and serum of head and neck cancer patients. Cancer Res. 2000, 60: 892-5.PubMed
23.
go back to reference Caone RB, Pai SI, Koch WM, Gillison ML, Danish HN, Westra WH, Daniel R, Shah KV, Sidransky D: Detection and quantitation of human papillomavirus (HPV) DNA in the sera of patients with HPV-associated head and neck squamous cell carcinoma. Clin Cancer Res. 2000, 6: 4171-5. Caone RB, Pai SI, Koch WM, Gillison ML, Danish HN, Westra WH, Daniel R, Shah KV, Sidransky D: Detection and quantitation of human papillomavirus (HPV) DNA in the sera of patients with HPV-associated head and neck squamous cell carcinoma. Clin Cancer Res. 2000, 6: 4171-5.
24.
go back to reference Fujiwara Y, Chi DD, Wang H, Keleman P, Morton DL, Turner R, Hoon DS: Plasma DNA microsatellites as tumor-specific markers and indicators of tumor progression in melanoma patients. Cancer Res. 1999, 59: 1567-1571.PubMed Fujiwara Y, Chi DD, Wang H, Keleman P, Morton DL, Turner R, Hoon DS: Plasma DNA microsatellites as tumor-specific markers and indicators of tumor progression in melanoma patients. Cancer Res. 1999, 59: 1567-1571.PubMed
25.
go back to reference Silva JM, Dominguez G, Garcia JM, Gonzalez R, Villanueva MJ, Navarro F, Provencio M, San Martin S, Espana P, Bonilla F: Presence of tumor DNA in plasma of breast cancer patients: clinicopathological correlations. Cancer Res. 1999, 59: 3251-3256.PubMed Silva JM, Dominguez G, Garcia JM, Gonzalez R, Villanueva MJ, Navarro F, Provencio M, San Martin S, Espana P, Bonilla F: Presence of tumor DNA in plasma of breast cancer patients: clinicopathological correlations. Cancer Res. 1999, 59: 3251-3256.PubMed
26.
go back to reference Yamada T, Nakamori S, Ohzato H, Oshima S, Aoki T, Higaki N, Sugimoto K, Akagi K, Fujiwara Y, Nishisho I, Sakon M, Gotoh M, Monden M: Detection of K-ras gene mutations in plasma DNA of patients with pancreatic adenocarcinoma: correlation with clinicopathological features. Clin Cancer Res. 1998, 4: 1527-32.PubMed Yamada T, Nakamori S, Ohzato H, Oshima S, Aoki T, Higaki N, Sugimoto K, Akagi K, Fujiwara Y, Nishisho I, Sakon M, Gotoh M, Monden M: Detection of K-ras gene mutations in plasma DNA of patients with pancreatic adenocarcinoma: correlation with clinicopathological features. Clin Cancer Res. 1998, 4: 1527-32.PubMed
27.
go back to reference Pao CC, Hor JJ, Yang FP, Lin CY, Tseng CJ: Detection of human papillomavirus mRNA and cervical cancer cells in peripheral blood of cervical cancer patients with metastasis. J Clin Oncol. 1997, 15: 1008-1012.PubMed Pao CC, Hor JJ, Yang FP, Lin CY, Tseng CJ: Detection of human papillomavirus mRNA and cervical cancer cells in peripheral blood of cervical cancer patients with metastasis. J Clin Oncol. 1997, 15: 1008-1012.PubMed
28.
go back to reference Czegledy J, Iosif C, Hansson BG, Evander M, Gergely L, Wadell G: Can a test for E6/E7 transcripts of human papillomavirus type 16 serve as a diagnostic tool for the detection of micrometastasis in cervical cancer?. Int J Cancer. 1995, 64: 211-5.CrossRefPubMed Czegledy J, Iosif C, Hansson BG, Evander M, Gergely L, Wadell G: Can a test for E6/E7 transcripts of human papillomavirus type 16 serve as a diagnostic tool for the detection of micrometastasis in cervical cancer?. Int J Cancer. 1995, 64: 211-5.CrossRefPubMed
29.
go back to reference Sorenson GD, Porter DM, Barth RJ, Memoli VA, Rhodes CH, Karagas M, Tosteson TD, Bzik DJ: Detection of mutated KRAS2 sequences in plasma from patients with pancreatic carcinoma in comparison with the Ca19-9 assay. J Int Soc Oncodev Biol Med. 1997, 18: 66- Sorenson GD, Porter DM, Barth RJ, Memoli VA, Rhodes CH, Karagas M, Tosteson TD, Bzik DJ: Detection of mutated KRAS2 sequences in plasma from patients with pancreatic carcinoma in comparison with the Ca19-9 assay. J Int Soc Oncodev Biol Med. 1997, 18: 66-
30.
go back to reference Anker P, Lyautey J, Lefort F, Lederrey C, Stroun M: Transformation of NIH/3T3 cells and SW 480 cells displaying K-ras mutation. C R Acad Sci III. 1994, 317: 869-74.PubMed Anker P, Lyautey J, Lefort F, Lederrey C, Stroun M: Transformation of NIH/3T3 cells and SW 480 cells displaying K-ras mutation. C R Acad Sci III. 1994, 317: 869-74.PubMed
31.
go back to reference Garcia-Olmo D, Garcia-Olmo DC, Ontanon J, Martinez E, Vallejo M: Tumor DNA circulating in the plasma might play a role in metastasis: the hypothesis of the genometastasis. Histopathol. 1999, 4: 1159-1164. Garcia-Olmo D, Garcia-Olmo DC, Ontanon J, Martinez E, Vallejo M: Tumor DNA circulating in the plasma might play a role in metastasis: the hypothesis of the genometastasis. Histopathol. 1999, 4: 1159-1164.
Metadata
Title
Human papillomavirus DNA in plasma of patients with cervical cancer
Authors
Wichai Pornthanakasem
Kanjana Shotelersuk
Wichai Termrungruanglert
Narin Voravud
Somchai Niruthisard
Apiwat Mutirangura
Publication date
01-12-2001
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2001
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/1471-2407-1-2

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