Predictive value of HPV DNA in lymph nodes in surgically treated cervical carcinoma patients—A prospective study

Łukaszuk, Krzysztof; Liss, Joanna; Gulczyński, Jacek; Nowaczyk, Monika; Nakonieczny, Miroslaw; Piatkowski, M.; Sliwiński, W; Baay, Marc; Woźniak, Izabela; Maj, Bozena; Łukaszuk, Mariusz

doi:10.1016/j.ygyno.2006.10.018

Cited by 22 publications

(30 citation statements)

References 24 publications

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“…As reported by Fule et al [2006] and Chan et al [2005] the present data do not support that the presence of HPV DNA in histological-free lymph nodes is associated with a poor prognosis; most of the patients (83%) remained asymptomatic for 5-10 years post-surgery, including one patient with nodal metastasis who also remained asymptomatic, probably due to the excision of all the PLNs involved. A recent report [Lukaszuk et al, 2007] seems to disagreed with the conclusions of this study. They found that the survival of the patient group with metastasis positive PLN did not statistically differ from the patient group with metastasis negative/HPV positive PNL, and they concluded that the presence of HPV DNA in lymph node is probably an early metastasis.…”

Section: Discussioncontrasting

confidence: 97%

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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Section: Discussioncontrasting

confidence: 97%

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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“…Furthermore, in women with cervical cancer, although numerous publications have suggested that the presence of HPV DNA in LNs could be an early indicator of relapse and poor prognosis [28][29][30][31][32] , the significance of this association remains controversial. In patients with OPSCC, this relationship has not been well investigated to date.…”

Section: Discussionmentioning

confidence: 99%

The Presence of HPV DNA in Neck Lymph Node Metastasis Correlates with Improved Overall Survival of Patients with Oropharyngeal Cancer Undergoing Surgical Treatment

Shimura

Hama²,

Suda³

et al. 2016

Oncology

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Background: Few studies have addressed how human papilloma virus (HPV) infection in oropharyngeal squamous cell carcinoma (OPSCC) affects the outcome of surgical therapy; furthermore, the relationship between the presence of HPV DNA and neck lymph node (LN) metastasis has not been well established. Methods: A total of 65 patients who underwent surgery as a first-line therapy for OPSCC were enrolled in this study. In HPV-positive patients, the presence of HPV DNA in metastatic neck LN lesions was evaluated. Results: The HPV-positive patients had significantly better overall survival than the HPV-negative patients (log-rank test, p = 0.04), whereas HPV infection status did not significantly affect disease-free survival (log-rank test, p = 0.65). In all of the HPV-positive OPSCC patients who developed cervical LN metastasis, the same HPV DNA type was found in both the primary tumour and the metastases. Conclusions: The present results suggest that HPV infection is a determining factor for good prognosis in patients undergoing first-line surgical therapy for OPSCC.

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“…Detection of HPV DNA in histologically normal lymph nodes of patients with cervix, vulva and penis cancer, using highly sensitive technologies such as PCR, has led to speculation that it could indicate an early metastasis or micrometastasis overlooked in the histological test [11][12][13][14][15][16]. Nodal metastasis is an important parameter in postoperative adjuvant therapy decisions, given its strong correlation with recurrence.…”

Section: Viral Dna Extraction From Tumorsmentioning

confidence: 99%

“…However, the results of different studies have been controversial. [13][14][15][16]. In our previous study group, it was noted that the presence of HPV DNA in tumor free PLNs did not necessarily indicate metastasis, but could be associated with an active immune reaction [14].…”

Section: Viral Dna Extraction From Tumorsmentioning

confidence: 99%

Detection of E6/E7 human papilloma virus (HPV) transcripts in lymph nodes of patients with cervical cancer

Basiletti¹,

Soderini²,

Picconi³

et al. 2017

Integr Cancer Sci Therap

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Volume 4(5): [1][2][3][4][5] types that taxonomically correspond to A7 (HPV 18, 39, 45, 59 and 68) and A9 species (HPV 16,31, 33, 35, 52 and 58) Hospital Nacional "Profesor Alejandro Posadas", Argentina 5Hospital Municipal "Juan A. Fernández", Argentina AbstractPersistent high risk Human Papillomavirus (HPV) infection is necessary for the development of cervical cancer (CC). HPV carcinogenesis is based on viral E6 and E7 proteins' capacity to interfere in cell proliferation control. The metastasis status of pelvic lymph nodes (PLN) is a critical parameter in post-operative decisions on adjuvant therapy, given its strong correlation with recurrence in CC. In order to complement the histopathological evaluation of subclinical node metastases, we evaluated the application of a commercial HPV E6 / E7 mRNA kit, to detect viral messenger RNAs in lymph nodes and tumors of patients with CC.Forty five cervical primary tumors and 152 PLN ( 3-4 from each patient) were included. HPVs were typed in tumors by PCR (polymerase chain reaction) using generic primers PGMY and reverse line blot hybridization (RLB) with type-specific oligo probes corresponding to 37 HPV types that infect the anogenital tract. PNL were collected in RNAlater (Invitrogen) and mRNA was extracted using the MiniMag (Biomerieux) system. Detection of E6 and E7 mRNAs corresponding to HPVs types 16, 18, 31, 33 and 45 was carried out using isothermal real time PCR (NucliSENS EasyQ HPV, Biomerieux).HPV was detected in the tumors of 42 patients; the viral types identified were HPV16 (n = 32), HPV18 (n = 5), HPV31 (n = 3), HPV45 (n = 2), HPV59 (n = 1) and HPV73 (n = 1). These last 2 cases were not considered in the study because the mRNA detection system does not include these viral types. Also excluded were 2 cases whose tumors were HPV negative. There was a high correlation between the histological and virological results. Seventy-two percent of the histologically positive PLN were positive for E6-E7 mRNA; while 93% (125/134) of the negative PLN were also negative for E6-E7 mRNA assay. There was, however 8% (9/134) of negative PLN in which viral messengers were detected.Patients' follow up was limited (4 years) and except for two patients who died (both positive for HPV 45) in the period under review, no recurrences were recorded in any of the patients included in the study.The presence of HPV in PLN may indicate a metastasis, as since the virus is not able of producing viremia or invading tissues it can only be "transported" by the cancer cell. The presence of HPV mRNA indicates viral genome transcription, a process which occurs in a lymph node only in CC metastatic cells, as these viruses can only replicate in epithelial-origin cells. Therefore, the findings of these mRNAs in the negative pelvic lymph nodes point out a very early metastasis, detectable at molecular level, but unobservable on histological diagnosis.The commercial kits for HPV E6/E7 mRNA detection, usually applied for the cervical disease management, may be used also to evaluate PLN biopsie...

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Predictive value of HPV DNA in lymph nodes in surgically treated cervical carcinoma patients—A prospective study

Cited by 22 publications

References 24 publications

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

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

The Presence of HPV DNA in Neck Lymph Node Metastasis Correlates with Improved Overall Survival of Patients with Oropharyngeal Cancer Undergoing Surgical Treatment

Detection of E6/E7 human papilloma virus (HPV) transcripts in lymph nodes of patients with cervical cancer

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