Human Papillomavirus DNA in Distant Metastases of Cervical Cancer

Ikenberg, Hans; Teufel, G.; Schmitt, B.; Kommoss, Friedrich; B, Stanimirović; Pfleiderer, Albrecht

doi:10.1006/gyno.1993.1009

Cited by 42 publications

(25 citation statements)

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“…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: 73%

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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mentioning

confidence: 73%

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 detection of HPV DNA in the metastatic lymph nodes of patients with CCs was first reported in 1986, by Lancaster et al30 More recently, other authors have demonstrated that distant metastases from HPV-related tumors can also contain the virus 31. On the other hand, a variable proportion of nonmetastatic lymph nodes harboring oncogenic HPV have also been described.…”

Section: Discussionmentioning

confidence: 96%

A very rare case of HPV-53-related cervical cancer, in a 79-year-old woman with a previous history of negative Pap cytology

Zappacosta¹,

Lattanzio²,

Viola³

et al. 2014

CIA

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The introduction of organized cervical cancer (CC) screening programs has drastically reduced the prevalence of CC. However the incidence is still too high, especially among elderly women. All guidelines strongly recommend a regular Papanicolaou (Pap) testing for young and middle-aged patients. On the other hand, many international professional societies no longer advise screening in women who have undergone hysterectomy, and in women aged 65 years and above, who have a previous history of regular Pap smears. Here we report the case of poorly differentiated CC, involving the pelvic lymph nodes and urinary bladder, occurring in a 79-year-old woman who regularly underwent Pap tests, with no reported cytological abnormalities. In this very rare case, the CC cells, as well as cells from metastatic lymph nodes and cells from urinary specimens, molecularly showed human papilloma virus (HPV)-53. With the limitations of a single case, this report brings important information to prevent CC in elderly patients: the utility of molecular tests to increase sensitivity of Pap smears in postmenopausal women; the importance of HPV-53 as one of the four “emergent” genotypes having a possible role in oncogenesis; and the presence of HPV-53 in lymph node metastases from cervical carcinoma, which would support the role of this virus in the maintenance of malignant status.

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“…This is again compatible with independent malignant conver sion events leading to a heterogeneous tumor. It should be stressed that these examples represent overall rare exceptions of the usual monoclonal pattern of tumors and métastasés observed in our and other laboratories' studies but tumor heterogeneity may also well explain apparently inconsistent findings such as HPV-negative métastasés of HPV-positive tumors, HPV-positive mé tastasés in patients with HPV-negative cancers [13] or a HPV-negative recurrence of a HPV-positive tumor [40], These observations do not impair the general utility of HPV-DNA screening as an additional, sensitive assay for métastasés but argue against its exclusive use in node evaluation.…”

Section: Discussionmentioning

confidence: 83%

Human Papillomavirus DNA in Genital Cancers, Metastases, and Lymph Nodes

Beyer-Finkler

Girardi²,

Sillem³

et al. 1995

Intervirology

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To evaluate the utility of human papillomavirus (HPV) DNA as molecular marker for diagnostic screening of lymph nodes for cancer metastases, we examined 16 involved and 124 histologically cancer-free nodes of 34 patients with cervical, vulval, or vaginal carcinomas associated with HPV 6, 16, 18, 31, 33, 45, or X. All metastases of HPV-positive tumors contained viral DNA of the same type as the primary cancer but in one case the copy number of viral genomes was dramatically reduced. In a varying proportion of histologically normal nodes of 7 of 23 patients with HPV 16-positive cancers HPV 16 DNA was revealed by Southern blot hybridization and/or PCR. Histologic reevaluation showed a metastasis in one case. Three examples of tumor heterogeneity regarding physical state or copy number of viral DNA are presented. Tumor heterogeneity is discussed as possible explanation for apparently inconsistent results such as HPV-negative metastases of HPV-positive tumors.

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Human Papillomavirus DNA in Distant Metastases of Cervical Cancer

Cited by 42 publications

References 0 publications

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

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

A very rare case of HPV-53-related cervical cancer, in a 79-year-old woman with a previous history of negative Pap cytology

Human Papillomavirus DNA in Genital Cancers, Metastases, and Lymph Nodes

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