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

Beyer-Finkler, Elke; Girardi, Fábio Muradás; Sillem, Martin; Pfister, Herbert

doi:10.1159/000150429

Cited by 13 publications

(9 citation statements)

References 23 publications

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“…Insofar as the PCRs used were sensitive [Cavuslu et al, 1996], detection of HPV-negative metastases from patients with HPV-positive tumours was surprising, though again this has been noted by others [Fuchs et al, 1989;Yanuck et al, 1991;Crook et al, 1992;Mvula et al, 1994]. The explanations for such cases are unknown but might include genetic heterogeneity or biclonal origin of metastatic tumour cells [Beyer-Finkler et al, 1995]. We also found HPV DNA in uninvolved (10) DO-1 This study a BCLL, B-cell chronic lymphocytic leukemia; NHL, HIV-1-associated non-Hodgkin's lymphoma; Ca, carcinoma; LN1, patients with metastatic or, LN2, uninvolved lymph nodes draining from a primary cervical carcinoma; CIN, cervical intraepithelial neoplasia; Ab, antibody used for detection of p53 overexpression.…”

Section: Discussionmentioning

confidence: 92%

Relationship between human papillomavirus infection and overexpression of p53 protein in cervical carcinomas and lymph node metastases

Çavuşlu

Goodlad²,

Hobbs³

et al. 1997

J. Med. Virol.

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Overexpression of p53 protein is common in cervical carcinoma. We investigated archival biopsies from 26 cervical cancer patients (24 with available lymph nodes) to determine the relationship between p53 overexpression and HPV infection at the cervix and lymph nodes. Twelve cervical carcinoma patients had p53 protein in cervical biopsies detectable by immunohistochemistry using monoclonal antibody DO-1, and 22 were positive for HPV DNA in polymerase chain reaction assays (16, contained HPV-16; 3, HPV-18; and, 3 HPV-X). Seven cervical cancer patients had one or more lymph nodes positive for p53 protein, and all but one of these were concordantly p53 positive at the cervix. However, detection of p53 protein in cervical biopsies was predictive neither of the expression of p53 at draining lymph nodes (P > 0.1) nor of the occurrence of metastases (P > 0.1). Fourteen patients were positive at one or more lymph nodes for HPV DNA. Cervical positivity for HPV DNA was associated significantly with concordant HPV positivity at the lymph nodes (P = 0.039) and was predictive of metastases (P = 0.019). There was no association between positivity for p53 and for HPV DNA at primary cervical carcinomas or at the lymph nodes (all P > 0.1). We conclude that, although detectable p53 protein is a common feature of cervical carcinomas, it is not predictive of metastases and is independent of HPV infection.

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Section: Discussionmentioning

confidence: 92%

Relationship between human papillomavirus infection and overexpression of p53 protein in cervical carcinomas and lymph node metastases

Çavuşlu

Goodlad²,

Hobbs³

et al. 1997

J. Med. Virol.

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“…These results are in keeping with those of Füle et al [21], showing the lack of any close correlation between metastasis and viral detection in lymph nodes. Beyer-Finkler et al [29] pointed out that lymph node HPV DNA might originate from disintegrating tumor cells, being conveyed passively by lymphatic flow or actively by phagocytic cells. Füle et al showed that, in highly heterogeneous advanced-stage tumors with numerous genetic original article Annals of Oncology aberrations, the loss of HPV DNA did not affect the proliferative capacity of cell clones [21].…”

Section: Discussionmentioning

confidence: 99%

Frequency and prognostic significance of HPV DNA in sentinel lymph nodes of patients with cervical cancer

Coutant¹,

Barranger²,

Cortez

et al. 2007

Annals of Oncology

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Background: It has been suggested that histologically undetectable or 'occult' metastases in the lymphatic system could explain some recurrences. HPV DNA screening by means of the polymerase chain reaction (PCR) has been proposed as a method to detect occult metastases. This study was designed to determine the frequency of HPV DNA detection by PCR in sentinel lymph node (SN), and its relation to the clinical characteristics and outcome of women with cervical cancer. Patients and methods:The primary cervical tumor and SN were tested for HPV DNA by means of PCR in 59 patients.Results: Fifteen (25.4%) of the 59 women undergoing the SN procedure had an involved SN. HPV DNA was more frequent in positive SN than in negative SN (P < 0.0001). Seven patients had a recurrence, after a mean delay of 17 months (range: 10-26). One of seven patients with a recurrence had an involved SN. HPV DNA was detected in an SN of one of seven patients with recurrence and nine (19.5%) of 46 patients without recurrence (not significant). Conclusion:In women with cervical cancer, HPV DNA screening of sentinel nodes might help to identify patients at risk of lymph node metastases and recurrence.

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“…On the other hand, even non-enlarged, non-metastatic cancer sometimes has a worse outcome despite a low clinical stage disease. Some studies have examined the prognostic value of HPV DNA detection in histological free PLN but so far a consensus has not been reached [Beyer-Finkler et al, 1995;Garzetti et al, 1998;Chan et al, 2005]. This study had two goals both to asses the prevalence and location of HPV types in tumors and lymph nodes and analyze the influence of H-ras mutations on the clinical course of the disease.…”

Section: Discussionmentioning

confidence: 99%

“…The role of HPV in the development of lymph node metastasis and adverse clinical outcome is poorly understood. Little is known about the intrinsic mechanisms involved in the metastatic process in HPV positive carcinoma, and it was suggested that HPV DNA in lymph nodes may indicate an early, subclinical metastasis [Beyer-Finkler et al, 1995;Garzetti et al, 1998;Chan et al, 2005].…”

Section: Introductionmentioning

confidence: 99%

Human papillomavirus and mutated H‐ras oncogene in cervical carcinomas and pathological negative pelvic lymph nodes: A retrospective follow‐up

Landro

Dalbert

Picconi

et al. 2008

Journal of Medical Virology

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The metastasis status of pelvic lymph nodes (PLNs) seems to be a predictive factor of survival. It was suggested that the presence of HPV DNA and other biological markers in PLN may indicate a sub clinical early metastasis. The aim was to describe the prevalence and distribution patterns of HPV DNA and H-ras mutations in intra operatively obtained cervical tumors and PLN. Thirty-seven cervical tumors and 61 lymph node biopsies from 37 patients with cervical cancer were selected. HPV typing and location were performed by PCR/dot blot and in situ hybridization (ISH) respectively. PCR/RFLP was used to scan for mutations in H-ras. Hundred percent of the cervical cancers and 85% of the PLN were HPV positive; co-infection with more than one type was 27%. HPV 16 was detected alone or co-infecting with other types in 84% of tumors and 46% of PLN; the second most frequent viral type was HPV 18 (tumor: 27%; PLN: 20%). In PLN, HPV was located in nuclei or/and cytoplasm of lymphocytes, macrophages, endothelial, and /or stromal cells. H-ras mutations were identified in 5/24 (21%) of patients with cervical tumors showing poor or moderated differentiation. HPV DNA in histological tumor-free PLN not necessary indicate metastasis, but it may be associated to an active immune reaction. Mutated H-ras is probably involved in cervical carcinogenesis and its detection in tumor and metastasis free PLN may be related to early metastasis or recurrence in at least a subset of poorly differentiated cervical tumors.

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

Cited by 13 publications

References 23 publications

Relationship between human papillomavirus infection and overexpression of p53 protein in cervical carcinomas and lymph node metastases

Relationship between human papillomavirus infection and overexpression of p53 protein in cervical carcinomas and lymph node metastases

Frequency and prognostic significance of HPV DNA in sentinel lymph nodes of patients with cervical cancer

Human papillomavirus and mutated H‐ras oncogene in cervical carcinomas and pathological negative pelvic lymph nodes: A retrospective follow‐up

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