Human papillomavirus 16 dna in cervical cancers and in lymph nodes of cervical cancer patients: A diagnostic marker for early metastases?

Fuchs, Pawel G.; Girardi, Frank; Pfister, Herbert

doi:10.1002/ijc.2910430110

Cited by 95 publications

(67 citation statements)

References 21 publications

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“…Recently, similar data have emerged with respect to HPV-16-containing cervical carcinomas, a proportion of which have been found to contain episomal HPV DNA only (Fuchs et al, 1989;Matsukura et al, 1989;Cullen et al, 1991). Furthermore, Nasseri et al (1991) have found that the presence of HPV-16 E2-encoding transcripts does not affect the expression levels of the E7 protein in immortalized cervical keratinocytes suggesting that E2 interruption triggered by integration is not causally related to increased E7 expression.…”

Section: Discussionmentioning

confidence: 66%

Human papillomavirus (HPV) type 16 and 33 E6/E7 region transcripts in tonsillar carcinomas can originate from integrated and episomal HPV DNA

Snijders¹,

Meijer²,

Brule³

et al. 1992

Journal of General Virology

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This study was undertaken to determine whether human papillomavirus (HPV) E6/E7 gene transcription in tonsillar carcinomas is correlated with viral DNA integration. Therefore, tonsillar carcinomas containing HPV-16 (n = 2) and HPV-33 (n = 2) DNA were analysed for the viral physical state and transcription of the E6/E7 region. Southern blot analysis, DNA polymerase chain reaction (PCR) and, eventually, twodimensional gel electrophoresis revealed indications for the presence of only episomal DNA in the HPV-16-containing biopsies and only integrated DNA in one HPV-33-containing biopsy. The second HPV-33-containing carcinoma, from which one biopsy and two resected tumour specimens were analysed, showed a rather complex physical state profile. The biopsy of this tumour contained only episomal DNA, one resected tumour part contained only integrated DNA and the remaining tumour part contained both integrated and episomal HPV-33 DNA. Independent of the viral physical state, all biopsies and resected tumour parts tested showed the presence of E6/E7 transcripts as determined by RNA PCR. The results indicate that E6/E7 transcripts in tonsillar carcinomas can originate from integrated as well as episomal HPV DNA.

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Section: Discussionmentioning

confidence: 66%

Human papillomavirus (HPV) type 16 and 33 E6/E7 region transcripts in tonsillar carcinomas can originate from integrated and episomal HPV DNA

Snijders¹,

Meijer²,

Brule³

et al. 1992

Journal of General Virology

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“…However, this feature is not universal, and an estimated 30% of cervical cancers do not contain integrated HPV DNA (18,35). Highgrade lesions and cancers could be screened for E2 expression before a decision were made on whether E2 immunotherapy was appropriate, much as breast cancers are now screened for expression of the HER2/neu protein before Herceptin (trastuzamab; Genentech, San Francisco, Calif.) therapy is chosen (24,46).…”

Section: Discussionmentioning

confidence: 99%

Vaccination of Rabbits with an Adenovirus Vector Expressing the Papillomavirus E2 Protein Leads to Clearance of Papillomas and Infection

Brandsma

Shlyankevich²,

Zhang³

et al. 2004

J Virol

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Cervical cancer arises from lesions caused by infection with high-risk types of human papillomavirus (HPV).Therefore, vaccination against HPV could prevent carcinogenesis by preventing HPV infection or inducing lesion regression. HPV E2 protein is an attractive candidate for vaccine development because it is required for papilloma formation, is involved in all stages of the virus life cycle, and is expressed in all premalignant lesions as well as some cancers. This study reports vaccination against E2 protein using a rabbit model of papillomavirus infection. A recombinant adenovirus (Ad) vector expressing the E2 protein of cottontail rabbit papillomavirus (CRPV) was tested for therapeutic efficacy in CRPV-infected rabbits. Primary immunization with the Ad-E2 vaccine, compared to immunization with a control Ad vector, reduced the number of papillomaforming sites from 17 of 45 to 4 of 45. After booster immunization, vaccinated rabbits formed no new papillomas versus an additional 23 papillomas in rabbits that received the control vector. Papillomas in the Ad-E2 vaccinees were significantly smaller than those in the control rabbits, and all four papillomas in the Ad-E2 vaccinated rabbits regressed. No CRPV DNA was detected either in the regression sites or in sites that did not form papillomas, indicating that the vaccination led to clearance of CRPV from all infected sites.Human papillomaviruses (HPVs) cause cervical cancer, which affects about one-half million women worldwide annually (37, 51, 56). HPV-associated disease includes anal, vulvar (56), oral and other respiratory tract cancers (20), and nearly all skin cancers in patients with epidermodysplasia verruciformis (13). HPV infection is also implicated in nonmelanoma skin cancers in immunocompetent as well as immunodeficient patients (4-6, 13, 26, 29, 40). It has been estimated that 10% of the world's tumor burden is attributable to HPV infection (57).Cervical carcinogenesis begins with benign epithelial lesions induced by HPV. Because genital HPV infection is highly prevalent, many women are at risk (41). Progression to cervical cancer typically takes more than a decade, so cytological screening can detect high-grade lesions in time for treatment. However, present treatments do not cure all lesions in all patients, and recurrence is a common sequela. Furthermore, cervical cancer has a mortality rate of 33%, clearly indicating the need for better therapy.Because premalignant lesions caused by HPV can be detected early, vaccination against HPV antigens could provide an effective therapy to induce lesion regression and prevent cancer (9-12, 45). A therapeutic vaccine could also eliminate residual HPV infection after surgical removal of a lesion (9)(10)(11)(12)45). The viral E6 and E7 oncoproteins are presently popular targets for a therapeutic HPV vaccine. These proteins stimulate cellular proliferation, promote genetic instability, and transform cells, in large part by perturbing the p53 and retinoblastoma tumor suppressor pathways (reviewed in reference 38)...

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“…However, Cullen et al observed pure integrated HPV DNA, mixed forms and episomal forms in HPV 16 containing cancers, whereas all HPV 18 containing cancers revealed only integrated form (26); Matsukura et al detected exclusive episomal forms of HPV 16 DNA in infected cervical epithelium, albeit this form was present in 70% of investigated cervical malignancies (27)(28)(29).…”

Section: ------------------------------------------------------------mentioning

confidence: 99%

Significance of multiple HPV infection in cervical cancer patients and its impact on treatment response

et al. 1992

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Abstract. Human papilloma virus (HPV) is the major cause of invasive cervical cancer (ICC). The study aim was to determine the prevalence of HPV genotypes and to correlate HPV types with response to radiotherapy. A total of 43 cervical biopsies collected from sequentially enrolled patients were analyzed by DNA amplification with MY09/MY11 primers and sequenced to determine the HPV genotype. Samples with multiple infections were resolved by multiplex PCR, combined with array primer extension (APEX). HPV DNA was detected in 40 of 43 (93%) samples. Nine different HPVs, including the most common types -16 (53%) and -18 (13%) were detected. Other types were HPV 31, 33, 45, 52, 58, 66 and 68. Single HPV types were found in 33 of 40 samples (82%) and multiple types in 7 of 40 samples (18%). The following significant predictors were identified: a) HPV 58 was most significant (p=0.02), followed by HPV 18 (p=0.04) associated with lack of treatment response; b) tumor size (p=0.042) and treatment response (p=0.025) elicited association with HPV infection type; c) treatment failure were found to be nearly 5-fold higher in case of multiple infections than of single infection (57% versus 12%) (odds ratio = 9.66; 95% CI 1.6-6.00). d) Multiple HPV infections correlated most prominently with lack of treatment compared with single type infection (p=0.005). Hence, patients with multiple infections, large tumor size, and HPV 58 and/or 18, are at risk of treatment failure and need to be followed for response and suitable inter-ventions done for a favorable outcome.

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Human papillomavirus 16 dna in cervical cancers and in lymph nodes of cervical cancer patients: A diagnostic marker for early metastases?

Cited by 95 publications

References 21 publications

Human papillomavirus (HPV) type 16 and 33 E6/E7 region transcripts in tonsillar carcinomas can originate from integrated and episomal HPV DNA

Human papillomavirus (HPV) type 16 and 33 E6/E7 region transcripts in tonsillar carcinomas can originate from integrated and episomal HPV DNA

Vaccination of Rabbits with an Adenovirus Vector Expressing the Papillomavirus E2 Protein Leads to Clearance of Papillomas and Infection

Significance of multiple HPV infection in cervical cancer patients and its impact on treatment response

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