Human papillomavirus deoxyribonucleic acid in cervical carcinoma from primary and metastatic sites

Lancaster, Wayne D.; Castellano, Carlos; Santos, Carlos Roberto dos; Delgado, Gregorio; Kurman, Robert J.; Jenson, A. Bennett

doi:10.1016/0002-9378(86)90405-9

Cited by 131 publications

(39 citation statements)

References 12 publications

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“…agreement with earlier reports (Yoshikawa et al, 1985;Scholl et al, 1985 ;Lancaster et al, 1986;Meanwell et al, 1987). However some samples showed deletions or certain genomic rearrangements leading to an atypical pattern which also may be indicative of integration of HPV-16 DNA into the host cell genome (Lehn et al, 1985;Millan et al, 1986;Choo et al, 1987;Takebe et al, 1987;Wilczynski et al, 1988).…”

Section: Discussionsupporting

confidence: 91%

Analysis by polymerase chain reaction of the physical state of human papillomavirus type 16 DNA in cervical preneoplastic and neoplastic lesions

Das

Sharma

Gopalakrishna

et al. 1992

Journal of General Virology

141

120

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Integration of human papillomavirus (HPV) DNA into the host cell genome is believed to be essential for malignant progression. However unambiguous detection of the physical state of HPV is a difficult and timeconsuming procedure. To resolve this issue a simple, rapid and highly sensitive technique of polymerase chain reaction (PCR) has been utilized for detecting the physical state of HPV-16 DNA. Investigations were carried out in 122 cervical specimens comprising the whole spectrum of cervical lesions starting from cervical dysplasia to invasive carcinoma including HPV-16-positive normal controls. A pair of oligonucleotide primers specific to the E2 open reading frame, which is often deleted or disrupted following HPV integration, was used for the study. Distinction between episomal and integrated forms of viral DNA was accomplished by detecting amplification of the E2-specific fragment (1139 bp) in the PCR product. The PCR results were compared with those obtained by the conventional methods of Southern blotting, twodimensional gel electrophoresis and chromosomal in situ hybridization; a high degree of agreement was observed between the methods. The findings indicate that although integrated forms of HPV-16 DNA were detected in more than 70% of cervical cancer specimens, integration was less frequent (23%) in severe dysplasia and carcinoma in situ. Only 2.5 % of cases showed both episomal and integrated forms ofHPV-16 DNA. The difference between episomal and integrated forms was statistically significant (P<0.01). The absence of integration in about 30% of cancer cases suggests that integration of HPV may not be necessary for malignant progression and alternative mechanism(s) of malignant transformation may occur without HPV integration. The PCR test thus provides an effective complement to Southern blotting and twodimensional gel electrophoresis for accurate detection of the integration of HPV DNA.

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Section: Discussionsupporting

confidence: 91%

Analysis by polymerase chain reaction of the physical state of human papillomavirus type 16 DNA in cervical preneoplastic and neoplastic lesions

Das

Sharma

Gopalakrishna

et al. 1992

Journal of General Virology

141

120

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“…165 (4) The viral genome is present in the original tumour and in metastases. 166 (5) Most of the cell lines established from cervical cancer contain either HPV-16 or HPV-18 genomes. 167 (6) The pattern of transcription changes as the lesion increases in severity.…”

Section: Biological Plausibility and Coherencementioning

confidence: 99%

The causal relation between human papillomavirus and cervical cancer

Bosch

Lörincz²,

Muñóz

et al. 2002

Journal of Clinical Pathology

3,003

2,122

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“…The E6-E7 genes of HPV-16, which are expressed at high levels in cervical carcinomas, encode proteins that are capable of transcriptional regulation and cellular transformation through interactions with cellular proteins, such as the tumor suppressor gene products pRB and p53 (5). These functions suggest an important role of HPV-16 in the initiation of cervical cancers.The HPV-16 DNA is frequently found in metastases of cervical cancers in either local lymph nodes (6)(7)(8)(9)(10)(11)(12)(13)(14) or distant site (15). The same HPV DNA sequences are consistently detected in metastases and primary tumors from the same patients, suggesting the same origin of viral DNA, and in situ hybridization has demonstrated the HPV DNA within the nuclei of metastatic cells (9, 10).…”

mentioning

confidence: 99%

Metastatic conversion of cells by expression of human papillomavirus type 16 E6 and E7 genes.

Chen

Ashe

Singhal

et al. 1993

Proc. Natl. Acad. Sci. U.S.A.

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The There is convincing epidemiological and experimental evidence linking specific types of human papillomavirus (HPV) with the etiology of cervical cancer (1, 2). HPV-16 and -18 are present in >70% of cervical dysplasias and carcinomas, whereas HPV-6 and -11 are usually found in benign genital condyloma acuminata (3, 4). The E6-E7 genes of HPV-16, which are expressed at high levels in cervical carcinomas, encode proteins that are capable of transcriptional regulation and cellular transformation through interactions with cellular proteins, such as the tumor suppressor gene products pRB and p53 (5). These functions suggest an important role of HPV-16 in the initiation of cervical cancers.The HPV-16 DNA is frequently found in metastases of cervical cancers in either local lymph nodes (6)(7)(8)(9)(10)(11)(12)(13)(14) or distant site (15). The same HPV DNA sequences are consistently detected in metastases and primary tumors from the same patients, suggesting the same origin of viral DNA, and in situ hybridization has demonstrated the HPV DNA within the nuclei of metastatic cells (9, 10). HPV-16 DNA can also be detected in histologically negative lymph nodes (8, 11), suggesting that it may provide a sensitive indicator for early metastases. It is not known, however, whether the expression of HPV genes influences the ability of a tumor to metastasize, and it is controversial whether human cervical cancers with HPV-16 DNA are more invasive than those associated with nononcogenic HPV types or HPV-negative cancers (16)(17)(18).To investigate the relationship between the expression of HPV-16 genes and tumor metastasis, we have assessed the ability of murine cell lines expressing the E6 and E7 genes from oncogenic HPV-16 or nononcogenic HPV-6b to formThe publication costs of this article were defrayed in part by page charge payment. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. §1734 solely to indicate this fact. metastasis in a nude mouse model. We report here that the expression in mouse cell lines of the E6 and E7 genes from HPV-16, but not from HPV-6b, results in metastatic conversion. MATERIALS AND METHODSMice. Female BALB/c (nu/nu) mice, 4-8 weeks old, and C3H/HeN mice, 6-8 weeks old, were bought from HarlanSprague-Dawley.Cell Lines. NCTC2555 is a fibrosarcoma line of C3H/HeN mouse origin (19), and the NIH 3T3 fibroblast line is BALB/c mouse origin. The CaSki line was derived from a HPV-16-positive squamous cell carcinoma of human cervix. PA317 and t-2 are packaging cell lines for amphotropic or ecotropic retroviruses, respectively. YAC-1 is a natural killer (NK) cell-sensitive lymphoma line and EL-4 is a NK-resistant lymphoma line. All cells were purchased from American Type Culture Collection and were maintained at 37°C with Dulbecco's modified Eagle's medium (DMEM) containing 10% fetal calf serum (HyClone) in a humidified atmosphere of 5% C02/95% air.Gene Transfer by Recombinant Retroviruses. Retroviruses were prepared as described (20,21) at biosafety level 2....

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Human papillomavirus deoxyribonucleic acid in cervical carcinoma from primary and metastatic sites

Cited by 131 publications

References 12 publications

Analysis by polymerase chain reaction of the physical state of human papillomavirus type 16 DNA in cervical preneoplastic and neoplastic lesions

Analysis by polymerase chain reaction of the physical state of human papillomavirus type 16 DNA in cervical preneoplastic and neoplastic lesions

The causal relation between human papillomavirus and cervical cancer

Metastatic conversion of cells by expression of human papillomavirus type 16 E6 and E7 genes.

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