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Special Issue "Clinical Advances of Human Papillomaviruses"

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A special issue of Journal of Clinical Medicine (ISSN 2077-0383).

Deadline for manuscript submissions: closed (30 September 2014)

Special Issue Editors

Guest Editor
Prof. Dr. Stephen K. Tyring

The University of Texas, Medical School at Houston, 1401 Binz, Suite 200, Houston, TX 77004, USA
Website | E-Mail
Fax: +713 524 3432
Interests: cutaneous infectious diseases; cutaneous immunology; cutaneous oncology
Guest Editor
Dr. Christopher Downing

Center for Clinical Studies, 1401 Binz Ave, Suite 200, Houston, TX 77004, USA
Website | E-Mail
Fax: +281 335 4605
Interests: psoriasis; atopic dermatitis; HPV; HSV; postherpetic neuralgia
Guest Editor
Dr. Jacqueline Guidry

Center for Clinical Studies, 1401 Binz Ave, Suite 200, Houston, TX 77004 USA
Website | E-Mail
Phone: +713 528 8818
Fax: +713 528 8848
Interests: psoriasis; HPV; HSV; atopic dermatitis; acne

Special Issue Information

Dear Colleagues,

The human papillomavirus (HPV) is responsible for the majority of newly acquired sexually transmitted infections (STIs) in the United States (in the year 2013). HPV is also an essential carcinogen; it is increasingly implicated in association with cancers occurring at numerous sites of the body, including the oropharynx. The virus is well-known as the cause of nearly 100 percent of all cervical cancers. The significant health and economic burdens of disease continue to stimulate research on the virus, with special interest in decreasing disease transmissibility through vaccination and improvements in cancer screening. Recent screening advancements by national health organizations have guided physicians in the way they screen for cervical cancer with respect to starting and stopping age, frequency, and select groups for which the standard recommendations do not apply. Although there is not currently any specific treatment for the HPV infection, the diseases it causes are treatable. Two vaccines have been developed against HPV infection: the bivalent and quadrivalent vaccines approved in 2006 for use in women and the quadrivalent vaccine approved in 2009 for use in men (as well as women).

This Special Issue is composed of articles that reflect the latest developments of the human papillomaviruses, with additional focus on anticipated advances of the disease.

Prof. Dr. Stephen Tyring
Dr. Christopher Downing
Dr. Jacqueline Guidry
Guest Editors

Submission

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. Papers will be published continuously (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are refereed through a peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Journal of Clinical Medicine is an international peer-reviewed Open Access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 300 CHF (Swiss Francs). English correction and/or formatting fees of 250 CHF (Swiss Francs) will be charged in certain cases for those articles accepted for publication that require extensive additional formatting and/or English corrections.


Keywords

  • HPV
  • Virology
  • cervical cancer
  • vaccination
  • pap smear
  • warts
  • Gardasil
  • Cervarix

Published Papers (10 papers)

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Review

Open AccessReview Cutaneous Squamous Cell Carcinomas in Organ Transplant Recipients
J. Clin. Med. 2015, 4(6), 1229-1239; doi:10.3390/jcm4061229
Received: 9 May 2015 / Revised: 27 May 2015 / Accepted: 28 May 2015 / Published: 3 June 2015
Cited by 6 | PDF Full-text (111 KB) | HTML Full-text | XML Full-text
Abstract
Non-melanoma skin cancers represent a major cause of morbidity after organ transplantation. Squamous cell carcinomas (SCC) are the most common cutaneous malignancies seen in this population, with a 65–100 fold greater incidence in organ transplant recipients compared to the general population. In recent
[...] Read more.
Non-melanoma skin cancers represent a major cause of morbidity after organ transplantation. Squamous cell carcinomas (SCC) are the most common cutaneous malignancies seen in this population, with a 65–100 fold greater incidence in organ transplant recipients compared to the general population. In recent years, human papillomaviruses (HPV) of the beta genus have been implicated in the pathogenesis of post-transplant SCCs. The underlying mechanism of carcinogenesis has been attributed to the E6 and E7 proteins of HPV. Specific immunosuppressive medications, such as the calcineurin inhibitors and azathioprine, are associated with a higher incidence of post-transplant SCCs compared to other immunosuppressive agents. Compared to other immunosuppressives, mTOR inhibitors and mycophenolate mofetil have been associated with a decreased risk of developing post-transplant non-melanoma skin cancers. As a result, they may represent ideal immunosuppressive medications in organ transplant recipients. Treatment options for post-transplant SCCs include surgical excision, Mohs micrographic surgery, systemic retinoid therapy, adjunct topical therapy, electrodessication and curettage, and radiation therapy. This review will discuss the epidemiology, risk factors, and management options of post-transplant SCCs. In addition, the underlying mechanisms of beta-HPV mediated carcinogenesis will be discussed. Full article
(This article belongs to the Special Issue Clinical Advances of Human Papillomaviruses)
Open AccessReview Human Papillomavirus: Current and Future RNAi Therapeutic Strategies for Cervical Cancer
J. Clin. Med. 2015, 4(5), 1126-1155; doi:10.3390/jcm4051126
Received: 27 January 2015 / Accepted: 8 May 2015 / Published: 21 May 2015
PDF Full-text (687 KB) | HTML Full-text | XML Full-text
Abstract
Human papillomaviruses (HPVs) are small DNA viruses; some oncogenic ones can cause different types of cancer, in particular cervical cancer. HPV-associated carcinogenesis provides a classical model system for RNA interference (RNAi) based cancer therapies, because the viral oncogenes E6 and E7 that cause
[...] Read more.
Human papillomaviruses (HPVs) are small DNA viruses; some oncogenic ones can cause different types of cancer, in particular cervical cancer. HPV-associated carcinogenesis provides a classical model system for RNA interference (RNAi) based cancer therapies, because the viral oncogenes E6 and E7 that cause cervical cancer are expressed only in cancerous cells. Previous studies on the development of therapeutic RNAi facilitated the advancement of therapeutic siRNAs and demonstrated its versatility by siRNA-mediated depletion of single or multiple cellular/viral targets. Sequence-specific gene silencing using RNAi shows promise as a novel therapeutic approach for the treatment of a variety of diseases that currently lack effective treatments. However, siRNA-based targeting requires further validation of its efficacy in vitro and in vivo, for its potential off-target effects, and of the design of conventional therapies to be used in combination with siRNAs and their drug delivery vehicles. In this review we discuss what is currently known about HPV-associated carcinogenesis and the potential for combining siRNA with other treatment strategies for the development of future therapies. Finally, we present our assessment of the most promising path to the development of RNAi therapeutic strategies for clinical settings. Full article
(This article belongs to the Special Issue Clinical Advances of Human Papillomaviruses)
Open AccessReview Current Cervical Carcinoma Screening Guidelines
J. Clin. Med. 2015, 4(5), 918-932; doi:10.3390/jcm4050918
Received: 7 April 2015 / Revised: 23 April 2015 / Accepted: 23 April 2015 / Published: 7 May 2015
PDF Full-text (85 KB) | HTML Full-text | XML Full-text
Abstract
A formidable threat to the health of women, cervical carcinoma can be prevented in many cases with adequate screening. The current guidelines for cervical carcinoma screening were created as joint recommendations of the American Cancer Society (ACS), the American Society for Colposcopy and
[...] Read more.
A formidable threat to the health of women, cervical carcinoma can be prevented in many cases with adequate screening. The current guidelines for cervical carcinoma screening were created as joint recommendations of the American Cancer Society (ACS), the American Society for Colposcopy and Cervical Pathology (ASCCP) and the American Society for Clinical Pathology (ASCP) in 2012, and later accepted and promoted by the American Congress of Obstetricians and Gynecologists (ACOG). The 2012 recommendations underscore the utility of molecular testing as an adjunct to cytology screening for certain women and provide guidance to clinicians based on different risk-benefit considerations for different ages. This manuscript will review screening techniques and current recommendations for cervical cancer screening and human papilloma virus (HPV) testing, as well as possible future screening strategies. Full article
(This article belongs to the Special Issue Clinical Advances of Human Papillomaviruses)
Open AccessReview Advancements in the Management of HPV-Associated Head and Neck Squamous Cell Carcinoma
J. Clin. Med. 2015, 4(5), 822-831; doi:10.3390/jcm4050822
Received: 24 October 2014 / Revised: 5 March 2015 / Accepted: 6 March 2015 / Published: 24 April 2015
PDF Full-text (56 KB) | HTML Full-text | XML Full-text
Abstract
Head and neck carcinomas have long been linked to alcohol and tobacco abuse; however, within the last two decades, the human papillomavirus (HPV) has emerged as a third etiology and is specifically associated with head and neck squamous cell carcinomas (HNSCC). In this
[...] Read more.
Head and neck carcinomas have long been linked to alcohol and tobacco abuse; however, within the last two decades, the human papillomavirus (HPV) has emerged as a third etiology and is specifically associated with head and neck squamous cell carcinomas (HNSCC). In this anatomical region, the oncogenic HPV-16 mediates transformation and immortalization of epithelium, most commonly in the oropharynx. Nevertheless, the recent identification of novel HPV mechanisms thought to be specific to oropharyngeal carcinogenesis has coincided with observations that HPV-associated HNSCC has differing clinical behavior—in terms of natural history, therapeutic response, and prognosis—than HPV-negative head and neck tumors. Taken together with the growing incidence of HPV transmission in younger populations, these discoveries have sparked a rapid expansion in both laboratory and clinical studies on the infection and disease. Herein, we review the clinical characteristics of HPV-associated HNSCC, with particular emphasis on recent advancements in our understanding of the management of this infectious malignancy. Full article
(This article belongs to the Special Issue Clinical Advances of Human Papillomaviruses)
Open AccessReview Advancements in Pharmacotherapy for Noncancerous Manifestations of HPV
J. Clin. Med. 2015, 4(5), 832-846; doi:10.3390/jcm4050832
Received: 1 December 2014 / Revised: 7 April 2015 / Accepted: 14 April 2015 / Published: 24 April 2015
Cited by 4 | PDF Full-text (174 KB) | HTML Full-text | XML Full-text
Abstract
Human papillomavirus (HPV) is the most common sexually transmitted disease. Via infection of the basal epithelial cells, HPV causes numerous malignancies and noncancerous cutaneous manifestations. Noncancerous cutaneous manifestations of HPV, including common, plantar, plane, and anogenital warts, are among the most common reasons
[...] Read more.
Human papillomavirus (HPV) is the most common sexually transmitted disease. Via infection of the basal epithelial cells, HPV causes numerous malignancies and noncancerous cutaneous manifestations. Noncancerous cutaneous manifestations of HPV, including common, plantar, plane, and anogenital warts, are among the most common reasons for an office visit. Although there are various therapies available, they are notoriously difficult to treat. HPV treatments can be grouped into destructive (cantharidin, salicylic acid), virucidal (cidofovir, interferon-α), antimitotic (bleomycin, podophyllotoxin, 5-fluorouracil), immunotherapy (Candida antigen, contact allergen immunotherapy, imiquimod) or miscellaneous (trichloroacetic acid, polyphenon E). The mechanism of action, recent efficacy data, safety profile and recommended regimen for each of these treatment modalities is discussed. Full article
(This article belongs to the Special Issue Clinical Advances of Human Papillomaviruses)
Open AccessReview Safety and Efficacy Data on Vaccines and Immunization to Human Papillomavirus
J. Clin. Med. 2015, 4(4), 614-633; doi:10.3390/jcm4040614
Received: 30 September 2014 / Revised: 9 February 2015 / Accepted: 17 February 2015 / Published: 3 April 2015
Cited by 13 | PDF Full-text (181 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Since the discovery of the causal association between human papillomavirus (HPV) and cervical cancer, efforts to develop an effective prophylactic vaccine to prevent high-risk HPV infections have been at the forefront of modern medical research. HPV causes 530,000 cervical cancer cases worldwide, which
[...] Read more.
Since the discovery of the causal association between human papillomavirus (HPV) and cervical cancer, efforts to develop an effective prophylactic vaccine to prevent high-risk HPV infections have been at the forefront of modern medical research. HPV causes 530,000 cervical cancer cases worldwide, which is the second most common cause of cancer deaths in women; a worldwide collaboration among epidemiologists, molecular biologists, vaccinologists, virologists, and clinicians helped lead to the development of two highly effective prophylactive HPV vaccines. The first, Gardasil, is a quadrivalent vaccine made up of recombinant HPV L1 capsid proteins from the two high-risk HPV types (16/18) responsible for 70% of cervical cancer cases as well as two low-risk HPV types (6/11) which are the causative agent for genital warts. The second, Cervarix, is a bivalent vaccine that was FDA approved three years after Gardasil and is also composed of L1 capsid proteins from HPV types 16/18. This review article focuses on the safety and efficacy data of both FDA-approved vaccines, as well as highlighting a few advances in future HPV vaccines that show promise in becoming additional treatment options for this worldwide disease. Full article
(This article belongs to the Special Issue Clinical Advances of Human Papillomaviruses)
Open AccessReview The Interaction between Human Immunodeficiency Virus and Human Papillomaviruses in Heterosexuals in Africa
J. Clin. Med. 2015, 4(4), 579-592; doi:10.3390/jcm4040579
Received: 15 December 2014 / Revised: 12 February 2015 / Accepted: 10 March 2015 / Published: 2 April 2015
Cited by 4 | PDF Full-text (136 KB) | HTML Full-text | XML Full-text
Abstract
Sub-Saharan Africa has the highest incidence of human papillomavirus (HPV) and cervical cancer in the world, which is further aggravated by the burden of human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) disease with invasive cervical cancer being an AIDS-defining cancer. The prevalence of HPV
[...] Read more.
Sub-Saharan Africa has the highest incidence of human papillomavirus (HPV) and cervical cancer in the world, which is further aggravated by the burden of human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) disease with invasive cervical cancer being an AIDS-defining cancer. The prevalence of HPV infection and associated disease is very high in HIV-infected people and continues to be a problem even after anti-retroviral therapy. In the genital tract, the interaction between HPV and HIV is complex, with infection with multiple HPV types reported to make both women and men more susceptible to HIV infection. Besides the national programmes to vaccinate girls against HPV and screen women for cervical cancer, there should be targeted cervical cancer screening, treatment and prevention programmes introduced into HIV treatment centres. There is evidence that in high HIV prevalence areas, HIV-positive women could cause increases in the prevalence of genital HPV infection in HIV-negative men and so increase the HPV circulating in the community. Condom use and circumcision reduce the acquisition of HIV-1, and also to some extent of HPV. This review will highlight what is known about the interaction of HIV and HPV, with an emphasis on research in Africa. Full article
(This article belongs to the Special Issue Clinical Advances of Human Papillomaviruses)
Open AccessReview Immune Dysregulation in Patients Persistently Infected with Human Papillomaviruses 6 and 11
J. Clin. Med. 2015, 4(3), 375-388; doi:10.3390/jcm4030375
Received: 4 December 2014 / Revised: 30 December 2014 / Accepted: 28 January 2015 / Published: 3 March 2015
Cited by 1 | PDF Full-text (385 KB) | HTML Full-text | XML Full-text
Abstract
Human Papillomaviruses (HPVs) 6 and 11 are part of a large family of small DNA viruses, some of which are commensal. Although much of the population can contain or clear infection with these viruses, there is a subset of individuals who develop persistent
[...] Read more.
Human Papillomaviruses (HPVs) 6 and 11 are part of a large family of small DNA viruses, some of which are commensal. Although much of the population can contain or clear infection with these viruses, there is a subset of individuals who develop persistent infection that can cause significant morbidity and on occasion mortality. Depending on the site of infection, patients chronically infected with these viruses develop either recurrent, and on occasion, severe genital warts or recurrent respiratory papillomas that can obstruct the upper airway. The HPV-induced diseases described are likely the result of a complex and localized immune suppressive milieu that is characteristic of patients with persistent HPV infection. We review data that documents impaired Langerhans cell responses and maturation, describes the polarized adaptive T-cell immune responses made to these viruses, and the expression of class select II MHC and KIR genes that associate with severe HPV6 and 11 induced disease. Finally, we review evidence that documents the polarization of functional TH2 and T-regulatory T-cells in tissues persistently infected with HPV6 and 11, and we review evidence that there is suppression of natural killer cell function. Together, these altered innate and adaptive immune responses contribute to the cellular and humoral microenvironment that supports HPV 6 and 11-induced disease. Full article
(This article belongs to the Special Issue Clinical Advances of Human Papillomaviruses)
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Open AccessReview HPV Carcinomas in Immunocompromised Patients
J. Clin. Med. 2015, 4(2), 260-281; doi:10.3390/jcm4020260
Received: 11 November 2014 / Revised: 13 December 2014 / Accepted: 19 December 2014 / Published: 29 January 2015
Cited by 7 | PDF Full-text (156 KB) | HTML Full-text | XML Full-text
Abstract
Human papillomavirus (HPV) infection is the most common sexually transmitted disease worldwide and can result in pre-malignancies or overt malignancies of the skin and mucosal surfaces. HPV-related illnesses are an important personal and public health problem causing physical, mental, sexual and financial detriments.
[...] Read more.
Human papillomavirus (HPV) infection is the most common sexually transmitted disease worldwide and can result in pre-malignancies or overt malignancies of the skin and mucosal surfaces. HPV-related illnesses are an important personal and public health problem causing physical, mental, sexual and financial detriments. Moreover, this set of malignancies severely affects the immunosuppressed population, particularly HIV-positive patients and organ-transplant recipients. There is growing incidence of HPV-associated anogenital malignancies as well as a decrease in the average age of affected patients, likely related to the rising number of high-risk individuals. Squamous cell carcinoma is the most common type of HPV-related malignancy. Current treatment options for HPV infection and subsequent disease manifestations include imiquimod, retinoids, intralesional bleomycin, and cidofovir; however, primary prevention with HPV vaccination remains the most effective strategy. This review will discuss anogenital lesions in immunocompromised patients, cutaneous warts at nongenital sites, the association of HPV with skin cancer in immunocompromised patients, warts and carcinomas in organ-transplant patients, HIV-positive patients with HPV infections, and the management of cutaneous disease in the immunocompromised patient. Full article
(This article belongs to the Special Issue Clinical Advances of Human Papillomaviruses)
Open AccessReview Recent Insights into the Control of Human Papillomavirus (HPV) Genome Stability, Loss, and Degradation
J. Clin. Med. 2015, 4(2), 204-230; doi:10.3390/jcm4020204
Received: 6 November 2014 / Revised: 5 December 2014 / Accepted: 18 December 2014 / Published: 27 January 2015
Cited by 4 | PDF Full-text (551 KB) | HTML Full-text | XML Full-text
Abstract
Most human papillomavirus (HPV) antiviral strategies have focused upon inhibiting viral DNA replication, but it is increasingly apparent that viral DNA levels can be chemically controlled by approaches that promote its instability. HPVs and other DNA viruses have a tenuous relationship with their
[...] Read more.
Most human papillomavirus (HPV) antiviral strategies have focused upon inhibiting viral DNA replication, but it is increasingly apparent that viral DNA levels can be chemically controlled by approaches that promote its instability. HPVs and other DNA viruses have a tenuous relationship with their hosts. They must replicate and hide from the DNA damage response (DDR) and innate immune systems, which serve to protect cells from foreign or "non-self" DNA, and yet they draft these same systems to support their life cycles. DNA binding antiviral agents promoting massive viral DNA instability and elimination are reviewed. Mechanistic studies of these agents have identified genetic antiviral enhancers and repressors, antiviral sensitizers, and host cell elements that protect and stabilize HPV genomes. Viral DNA degradation appears to be an important means of controlling HPV DNA levels in some cases, but the underlying mechanisms remain poorly understood. These findings may prove useful not only for understanding viral DNA persistence but also in devising future antiviral strategies. Full article
(This article belongs to the Special Issue Clinical Advances of Human Papillomaviruses)
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