Randomized Placebo-Controlled Evaluation of Intramuscular Interferon Beta Treatment of Recurrent Human Papillomavirus

González-Sánchez, José Luis; Martínez-Chéquer, Juan Carlos; Hernandez-Celaya, Maria Eugenia; Barahona-Bustillos, Edgar; Andrade-Manzano, Alejandro

doi:10.1097/00006250-200104000-00026

Cited by 6 publications

(7 citation statements)

References 18 publications

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“…IFN therapy proved to be beneficial in HPV infections such as condylomata acuminata , whereas the use of IFN therapy in HPV‐associated anogenital intraepithelial neoplasia has been assessed in several studies with contradicting results. Improved outcome for IFN‐treated patients was shown in some studies , whereas others reported no change in response rates between treated patients and controls . This might be attributed to the fact that local application seems to achieve better responses than systemic application .…”

Section: Prophylactic and Therapeutic Alternatives For Hpv‐positive Omentioning

confidence: 97%

Next‐generation treatment strategies for human papillomavirus‐related head and neck squamous cell carcinoma: where do we go?

Olthof

Straetmans

Snoeck

et al. 2011

Reviews in Medical Virology

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Oncogenic human papillomavirus (HPV) is currently recognised as a major risk factor for the development of head and neck squamous cell carcinomas (HNSCC). HPV is mostly detected in tumours arising from the oropharynx and more specifically from the tonsil. HPV-related tumours display clinical and molecular characteristics that are distinct from HPV-unrelated tumours, which are generally induced by alcohol and tobacco abuse. Detection of biologically active HPV in HNSCC has prognostic relevance, which warrants the separate classification of HPV-induced tumours and is a prerequisite for further optimisation of treatment protocols for this distinct group. Current guidelines for the treatment of oropharyngeal squamous cell carcinoma (OPSCC) have not incorporated specific treatment modalities for HPV-related tumours. The development of such treatment options is still in a preclinical phase or in early clinical trials. Recent data on treatment response of OPSCC have been obtained by retrospectively analysing HPV-status and indicate that patients with HPV-related tumours show a favourable prognosis, independent of the type of treatment. These patients may benefit from de-intensified treatment, which should be assessed in prospective clinical trials. The development and future use of new antiviral and immunomodulatory therapeutics may be instrumental in this approach to improve survival rates and decrease disease-and-treatment-related morbidity. In this review we will focus on present therapeutic HPV-targeting strategies and discuss future directions for de-intensified treatment of HPV-positive HNSCC.

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Section: Prophylactic and Therapeutic Alternatives For Hpv‐positive Omentioning

confidence: 97%

Next‐generation treatment strategies for human papillomavirus‐related head and neck squamous cell carcinoma: where do we go?

Olthof

Straetmans

Snoeck

et al. 2011

Reviews in Medical Virology

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“…Finally, six studies that met all the inclusion criteria were used (two randomized controlled trials and four observational studies). The studies were from two countries: one from Mexico 16 and five from China 12,17–20 . These studies included 303 patients, and the pooled effective rate of interferon was 61.50% (95% confidence interval [CI] 0.480–0.749).…”

Section: Resultsmentioning

confidence: 99%

REBACIN® is an optional intervention for persistent high‐risk human papillomavirus infection: A retrospective analysis of 364 patients

Yang

Teng

Ming

et al. 2020

Intl J Gynecology & Obste

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Background: Persistent high-risk human papillomavirus (hrHPV) infection is a crucial cause of cervical cancer, for which optimal pharmacological intervention remains unavailable. This study aimed at evaluating the therapeutic efficacy of REBACIN® in patients with persistent hrHPV infection. Methods: This study is a combination of a retrospective analysis and a meta-analysis. The retrospective analysis included 364 patients who were persistently infected with HPV for at least twelve months, between September 2015 and February 2019, and only received REBACIN® intervention. HPV DNA typing, HC2 hrHPV DNA, and ThinPrep cytologic tests were performed before and after REBACIN® intervention, to evaluate the therapeutic efficacy. The meta-analysis included trials evaluating the therapeutic efficacy of interferons. Results: After a follow-up period of three to six months, the overall effective rate of REBACIN® was 74.73% (272/364), which was higher than that of interferon (61.50%

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“…The interaction of E6 and p300/CBP may thus block the growth-suppressing effects of interferon and allow HPV infections to persist for extended periods of time. Interferon therapy has also been suggested as a treatment for highgrade HPV infections, but variable results have been observed in clinical trails (6,14,15). Previously, we reported that keratinocytes that maintain HPV-31 episomes are highly sensitive to interferon treatment but that resistant populations quickly appear (9).…”

Section: Discussionmentioning

confidence: 95%

Human Papillomavirus E6 Proteins Mediate Resistance to Interferon-Induced Growth Arrest through Inhibition of p53 Acetylation

Hebner

Beglin

Laimins

2007

J Virol

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The high-risk human papillomavirus (HPV) E6 and E7 proteins act cooperatively to mediate multiple activities in viral pathogenesis. For instance, E7 acts to increase p53 levels while E6 accelerates its rate of turnover through the binding of the cellular ubiquitin ligase E6AP. Interferons are important antiviral agents that modulate both the initial and persistent phases of viral infection. The expression of HPV type 16 E7 was found to sensitize keratinocytes to the growth-inhibitory effects of interferon, while coexpression of E6 abrogates this inhibition. Treatment of E7-expressing cells with interferon ultimately resulted in cellular senescence through a process that is dependent upon acetylation of p53 by p300/CBP at lysine 382. Cells expressing mutant forms of E6 that are unable to bind p300/CBP or bind p53 failed to block acetylation of p53 at lysine 382 and were sensitive to growth arrest by interferon. In contrast, mutant forms of E6 that are unable to bind E6AP remain resistant to the effects of interferon, demonstrating that the absolute levels of p53 are not the major determinants of this activity. Finally, p53 acetylation at lysine 382 was found not to be an essential determinant of other types of senescence such as that induced by overexpression of Ras in human fibroblasts. This study identifies an important physiological role for E6 binding to p300/CBP in blocking growth arrest of human keratinocytes in the presence of interferon and so contributes to the persistence of HPV-infected cells.The E6 and E7 oncoproteins of human papillomaviruses (HPVs) act cooperatively to immortalize and transform human keratinocytes, with one factor complementing the activity of the other. While E7 stabilizes p53, E6 acts to reduce levels by recruiting the cellular ubiquitin ligase E6AP to the p53 complex, resulting in increased rates of turnover (32). Similarly, E6 activates hTert expression, which, together with E7 inactivation of the RB pathway, acts to immortalize human primary cells (22). Additional pathways that may require the cooperative action of both viral proteins involve resistance to growth arrest and senescence induced by either high-level expression of cell cycle regulators such as Ras or exposure to extracellular agents such as interferon.Interferon is a major signaling component of the innate immune response to viral infection. Type I interferons, which consist primarily of alpha and beta types, induce the transcription of multiple genes via the Jak-Stat signaling pathway, leading to immunomodulatory, as well as growth-inhibitory, effects (7, 34). Recent work has linked the tumor suppressor p53 as a regulator of the interferon response induced upon viral infection (35). While p53 is not directly activated by type I interferons, it can modulate the interferon response, thereby playing a central role in the cellular response to viral infection.The p53 protein acts as a transcription factor that controls the expression of genes involved in cell cycle regulation, apoptosis, and senescence (23, 28). p53 ac...

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Randomized Placebo-Controlled Evaluation of Intramuscular Interferon Beta Treatment of Recurrent Human Papillomavirus

Cited by 6 publications

References 18 publications

Next‐generation treatment strategies for human papillomavirus‐related head and neck squamous cell carcinoma: where do we go?

Next‐generation treatment strategies for human papillomavirus‐related head and neck squamous cell carcinoma: where do we go?

REBACIN® is an optional intervention for persistent high‐risk human papillomavirus infection: A retrospective analysis of 364 patients

Human Papillomavirus E6 Proteins Mediate Resistance to Interferon-Induced Growth Arrest through Inhibition of p53 Acetylation

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