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Viruses
Special Issues
HPV and HPV Vaccine
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HPV and HPV Vaccine

A special issue of Viruses (ISSN 1999-4915). This special issue belongs to the section "Viral Immunology, Vaccines, and Antivirals".

Deadline for manuscript submissions: closed (31 May 2021) | Viewed by 46757

Special Issue Editor

Dr. Merilyn Hibma

E-Mail Website
Guest Editor
Department of Pathology, University of Otago, Dunedin, New Zealand
Interests: human papillomavirus; immune evasion; extracellular vesicles; cervical cancer; protective immunity.

Special Issue Information

Dear Colleagues, 

Human papillomaviruses (HPVs) are double-stranded DNA viruses with an 8 kb genome. In 2008, Harald zur Hausen was awarded the Nobel Prize ‘for his discovery of human papillomaviruses causing cervical cancer’. There are over 100 types of HPV, of which 13 are considered to be carcinogenic. Of those types, HPV 16 and 18 account for the greatest proportion of cases of cervical cancer, and HPV 16 is associated with 90% of HPV+ head and neck cancers. In addition, members of the beta-papillomaviruses are associated with cutaneous squamous cell carcinoma (cSCC) in patients with epidermodysplasia verruciformis, and may contribute to UV-induced cSCC. Several virus-like particle vaccines have been developed for HPV, including, more recently, a nonavalent vaccine. These vaccines have high prophylactic efficacy. 

In this Special Issue, we wish to explore current research in HPV and HPV vaccines. Topics of interest include, but are not limited to: 

  • the role of human papillomaviruses in cancer (including head and neck and skin cancer);
  • the immune response to HPV, including protective immunity;
  • animal papillomavirus studies that inform HPV immunity;
  • elucidation of the mechanisms of regulation of host immunity by human papillomavirus; and
  • HPV vaccines, including therapeutic vaccines targeting HPV.

Dr. Merilyn Hibma
Guest Editor

Manuscript Submission Information

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Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Viruses 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 2600 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • human papillomavirus
  • vaccine
  • oncogenesis
  • immune evasion
  • immune response

Published Papers (15 papers)

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Editorial

Jump to: Research, Review, Other

1 pages, 139 KiB  
Editorial
Special Issue: HPV and HPV Vaccines
by Merilyn Hibma
Viruses 2022, 14(2), 274; https://0-doi-org.brum.beds.ac.uk/10.3390/v14020274 - 28 Jan 2022
Viewed by 2093
Abstract
Our fundamental understanding of papillomaviruses and their interactions with their host, including their role in cancer and how the immune system responds to them, has made the elimination of cervical cancer a realistic global health goal [...] Full article
(This article belongs to the Special Issue HPV and HPV Vaccine)

Research

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18 pages, 2781 KiB  
Article
The Mouse Papillomavirus Epigenetic Signature Is Characterised by DNA Hypermethylation after Lesion Regression
by Allison M. Tschirley, Peter A. Stockwell, Euan J. Rodger, Oliver Eltherington, Ian M. Morison, Neil Christensen, Aniruddha Chatterjee and Merilyn Hibma
Viruses 2021, 13(10), 2045; https://0-doi-org.brum.beds.ac.uk/10.3390/v13102045 - 11 Oct 2021
Cited by 3 | Viewed by 2508
Abstract
Papillomaviruses (PVs) are double-stranded DNA tumour viruses that can infect cutaneous and mucosal epidermis. Human papillomavirus (HPV) types have been linked to the causality of cutaneous squamous cell carcinoma (cSCC); however, HPV DNA is not always detected in the resultant tumour. DNA methylation [...] Read more.
Papillomaviruses (PVs) are double-stranded DNA tumour viruses that can infect cutaneous and mucosal epidermis. Human papillomavirus (HPV) types have been linked to the causality of cutaneous squamous cell carcinoma (cSCC); however, HPV DNA is not always detected in the resultant tumour. DNA methylation is an epigenetic change that can contribute to carcinogenesis. We hypothesise that the DNA methylation pattern in cells is altered following PV infection. We tested if DNA methylation was altered by PV infection in the mouse papillomavirus (MmuPV1) model. Immunosuppressed mice were infected with MmuPV1 on cutaneous tail skin. Immunosuppression was withdrawn for some mice, causing lesions to spontaneously regress. Reduced representation bisulphite sequencing was carried out on DNA from the actively infected lesions, visibly regressed lesions, and mock-infected control mice. DNA methylation libraries were generated and analysed for differentially methylated regions throughout the genome. The presence of MmuPV1 sequences was also assessed. We identified 834 predominantly differentially hypermethylated fragments in regressed lesions, and no methylation differences in actively infected lesions. The promoter regions of genes associated with tumorigenicity, including the tumour suppressor protein DAPK1 and mismatch repair proteins MSH6 and PAPD7, were hypermethylated. Viral DNA was detected in active lesions and in some lesions that had regressed. This is the first description of the genome-wide DNA methylation landscape for active and regressed MmuPV1 lesions. We propose that the DNA hypermethylation in the regressed lesions that we report here may increase the susceptibility of cells to ultraviolet-induced cSCC. Full article
(This article belongs to the Special Issue HPV and HPV Vaccine)
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12 pages, 290 KiB  
Article
Anti-HPV16 Antibody Titers Prior to an Incident Cervical HPV16/31 Infection
by Ana Gradissimo, Viswanathan Shankar, Fanua Wiek, Lauren St. Peter, Yevgeniy Studentsov, Anne Nucci-Sack, Angela Diaz, Sarah Pickering, Nicolas F. Schlecht and Robert D. Burk
Viruses 2021, 13(8), 1548; https://0-doi-org.brum.beds.ac.uk/10.3390/v13081548 - 05 Aug 2021
Cited by 1 | Viewed by 1944
Abstract
The goal of this study was to investigate the serological titers of circulating antibodies against human papillomavirus (HPV) type 16 (anti-HPV16) prior to the detection of an incident HPV16 or HPV31 infection amongst vaccinated participants. Patients were selected from a prospective post-HPV vaccine [...] Read more.
The goal of this study was to investigate the serological titers of circulating antibodies against human papillomavirus (HPV) type 16 (anti-HPV16) prior to the detection of an incident HPV16 or HPV31 infection amongst vaccinated participants. Patients were selected from a prospective post-HPV vaccine longitudinal cohort at Mount Sinai Adolescent Health Center in Manhattan, NY. We performed a nested case–control study of 43 cases with incident detection of cervical HPV16 (n = 26) or HPV31 (n = 17) DNA who had completed the full set of immunizations of the quadrivalent HPV vaccine (4vHPV). Two control individuals whom had received three doses of the vaccine (HPV16/31-negative) were selected per case, matched on age at the first dose of vaccination and follow-up time in the study: a random control, and a high-risk control that was in the upper quartile of a sexual risk behavior score. We conducted an enzyme-linked immunosorbent assay (ELISA) for the detection of immunoglobulin G (IgG) antibodies specific to anti-HPV16 virus-like particles (VLPs). The results suggest that the average log antibody titers were higher among high-risk controls than the HPV16/31 incident cases and the randomly selected controls. We show a prospective association between anti-HPV16 VLP titers and the acquisition of an HPV16/31 incident infection post-receiving three doses of 4vHPV vaccine. Full article
(This article belongs to the Special Issue HPV and HPV Vaccine)
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11 pages, 1688 KiB  
Article
Multiple Human Papilloma Virus (HPV) Infections Are Associated with HSIL and Persistent HPV Infection Status in Korean Patients
by Moonsik Kim, Nora Jee-Young Park, Ji Yun Jeong and Ji Young Park
Viruses 2021, 13(7), 1342; https://0-doi-org.brum.beds.ac.uk/10.3390/v13071342 - 12 Jul 2021
Cited by 30 | Viewed by 3079
Abstract
Infections with multiple human papilloma virus (HPV) types have been reported, but their role in cervical carcinogenesis has not been fully elucidated. In this study, 236 cases with multiple HPV infection were examined and compared to 180 cases with single HPV infection. HPV [...] Read more.
Infections with multiple human papilloma virus (HPV) types have been reported, but their role in cervical carcinogenesis has not been fully elucidated. In this study, 236 cases with multiple HPV infection were examined and compared to 180 cases with single HPV infection. HPV genotyping was performed with cervico-vaginal swab specimens using multiplex (real-time) polymerase chain reaction (PCR). In multiple HPV infection, the most prevalent HPV genotype was HPV 53, followed by HPV 16, 58, 52, and 68. HPV 33, 35, 39, 51, 52, 53, 58, and 68 were high-risk-HPV (HR-HPV) genotypes that were more frequently detected in multiple HPV infection compared to that in single HPV infection. The association between multiple HPV infection and high-grade SIL (HSIL) was significantly stronger compared to that of single HPV infection and HSIL (p = 0.002). Patients with multiple HPV infection displayed persistent and longer duration of the HPV infection compared to patients with single HPV infection. Multiple HPV infections have distinct clinicopathologic characteristics. Since it is associated with persistent HPV infection, HSIL, and different HR-HPV strains in contrast to single HPV infection, the presence of multiple HPV infection should be reported; close follow up is warranted. Full article
(This article belongs to the Special Issue HPV and HPV Vaccine)
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17 pages, 7127 KiB  
Article
Identification of High-Risk Human Papillomavirus DNA, p16, and E6/E7 Oncoproteins in Laryngeal and Hypopharyngeal Squamous Cell Carcinomas
by Andrejs Lifsics, Valerija Groma, Maksims Cistjakovs, Sandra Skuja, Renars Deksnis and Modra Murovska
Viruses 2021, 13(6), 1008; https://0-doi-org.brum.beds.ac.uk/10.3390/v13061008 - 27 May 2021
Cited by 7 | Viewed by 2254
Abstract
Human papillomavirus (HPV) was proven to play a significant role in cancer development in the oropharynx. However, its role in the development of laryngeal (LSCC) and hypopharyngeal squamous cell carcinoma (HPSCC) remains to be clarified. High-risk HPV (HR-HPV) viral proteins E6 and E7 [...] Read more.
Human papillomavirus (HPV) was proven to play a significant role in cancer development in the oropharynx. However, its role in the development of laryngeal (LSCC) and hypopharyngeal squamous cell carcinoma (HPSCC) remains to be clarified. High-risk HPV (HR-HPV) viral proteins E6 and E7 are considered to be pertinent to HPV-related carcinogenesis. Hence, our aim was to estimate LSCC and HPSCC for HR-HPV DNA, p16, and E6/E7 oncoprotein status by using molecular virology and immunohistochemistry methods. The prevalence of HPV16 infection was 22/41 (53.7%) and 20/31 (64.5%) for LSCC and HPSCC, accordingly. The majority of HPV16+ tumor samples were stage III or IV. In most samples, the presence of either HPV16 E6 or HPV16 E7 viral protein in dysplastic or tumor cells was confirmed using immunohistochemistry. Our results suggest a high prevalence of HPV16 as a primary HR-HPV type in LSCC and HPSCC. The lack of HPV E6/E7 oncoproteins in some tumor samples may suggest either the absence of viral integration or the presence of other mechanisms of tumorigenesis. The utilization of p16 IHC as a surrogate marker of HR-HPV infection is impractical in LSCC and HPSCC. Full article
(This article belongs to the Special Issue HPV and HPV Vaccine)
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12 pages, 1027 KiB  
Article
Uptake of Human Papillomavirus Vaccine and Intention to Vaccinate among Healthy Pregnant Women in Serbia: A Cross-Sectional Study on Awareness, Knowledge, and Attitudes
by Ljiljana Markovic-Denic, Srboljub Milicevic, Jovana Todorovic, Vladimir Nikolic, Olivera Djuric, Vuk Marusic, Stefan Dugalic, Brankica Vasiljevic and Miroslava Gojnic-Dugalic
Viruses 2021, 13(5), 727; https://0-doi-org.brum.beds.ac.uk/10.3390/v13050727 - 21 Apr 2021
Cited by 1 | Viewed by 1964
Abstract
We aimed to assess awareness, knowledge, and attitudes of healthy pregnant women towards human papillomavirus (HPV), to estimate factors associated with a positive attitude towards HPV immunization and to assess the uptake of the vaccine among their children. A cross-sectional study was conducted [...] Read more.
We aimed to assess awareness, knowledge, and attitudes of healthy pregnant women towards human papillomavirus (HPV), to estimate factors associated with a positive attitude towards HPV immunization and to assess the uptake of the vaccine among their children. A cross-sectional study was conducted at the University Clinic of Gynecology and Obstetrics, Belgrade, Serbia among pregnant women attending their regular gynecological check-ups at the 12th gestational week. Knowledge about HPV and HPV vaccine was assessed using a specifically designed 12-item and 5-item questionnaires. Out of total 265 included women, 79.3% had heard of HPV, and 37.5% knew that HPV vaccine exists. HPV vaccine knowledge score was associated with higher odds for a positive attitude towards vaccination of both female (OR = 4.10, 95% CI 1.50–11.29) and male (OR = 3.71, 95% CI 1.52–9.01) child. The number of children (OR = 1.32, 95% CI 1.04–1.67) and high vaccine knowledge score (OR = 1.64 95% CI 1.13–2.39) were independent predictors associated with willingness to vaccinate child against HPV. The gynecologist was the preferable point of reference for information seeking about the HPV vaccine. Despite relatively high HPV awareness and knowledge among pregnant women in Serbia, about one-third of them are HPV vaccine aware, and are willing to vaccinate their children against HPV. Full article
(This article belongs to the Special Issue HPV and HPV Vaccine)
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16 pages, 288 KiB  
Article
Facilitators and Barriers to Take Up Clinician-Collected and Self-Collected HPV Tests among Chinese Men Who Have Sex with Men
by Zixin Wang, Yuan Fang, Ngai Sze Wong, Mary Ip, Xin Guo and Samuel Yeung Shan Wong
Viruses 2021, 13(4), 705; https://0-doi-org.brum.beds.ac.uk/10.3390/v13040705 - 19 Apr 2021
Cited by 4 | Viewed by 2107
Abstract
Regular tests for human papillomavirus (HPV) and early treatment could represent an important strategy for preventing anal cancers among men who have sex with men (MSM). This study investigated facilitators and barriers to take up clinician-collected and self-collected HPV tests among Chinese MSM. [...] Read more.
Regular tests for human papillomavirus (HPV) and early treatment could represent an important strategy for preventing anal cancers among men who have sex with men (MSM). This study investigated facilitators and barriers to take up clinician-collected and self-collected HPV tests among Chinese MSM. This study was based on the baseline sample of a longitudinal study promoting HPV vaccination among 350 Chinese MSM who had never received an HPV vaccination. The baseline survey was conducted from August 2019 to April 2020. The prevalence of any HPV tests uptake in lifetime was 19.1%; 4.9% had HPV infection in anus, genital, oral cavity, and other places. Among the participants, 20% and 76.8% intended to take up self-financed and free clinician-collected HPV tests, and 76.8% intended to use free self-collected HPV tests. After adjusting for significant background characteristics, perceived risk of HPV infection, and perceived benefits, barriers, cue to action, and self-efficacy related to HPV tests in general and/or specific to self-collected HPV tests were associated with behavioral intention to take up free clinician-collected and/or self-collected HPV tests. Less than 20% of Chinese MSM reported HPV tests uptake. Modifying perceptions related to HPV tests may be useful to increase HPV tests coverage in this group. Full article
(This article belongs to the Special Issue HPV and HPV Vaccine)
11 pages, 892 KiB  
Article
A Retrospective Cohort Study of Young Women Spontaneously Choosing to Be Vaccinated against HPV: Outcomes from Their First Cervical Cancer Screening Test
by Annarosa Del Mistro, Jessica Battagello, Luca Weis, Vittoria Bressan, Vittorio Selle, Mauro Ramigni, Alessandra Dal Zotto, Antonio Maggiolo, Silvia Gori, Helena Frayle, Marco Zappa, Manuel Zorzi and the Consensus Study Veneto Working Group
Viruses 2021, 13(3), 486; https://0-doi-org.brum.beds.ac.uk/10.3390/v13030486 - 16 Mar 2021
Cited by 4 | Viewed by 2040
Abstract
Background: Efficacy for cervical cancer prevention of opportunistic HPV vaccination in post-pubertal girls is lower than in 11-year-olds. Methods: Women born between 1986 and 1992 vaccinated at 15–25 years of age (at least one dose of 4-valent HPV vaccine) and screened at 24–27 [...] Read more.
Background: Efficacy for cervical cancer prevention of opportunistic HPV vaccination in post-pubertal girls is lower than in 11-year-olds. Methods: Women born between 1986 and 1992 vaccinated at 15–25 years of age (at least one dose of 4-valent HPV vaccine) and screened at 24–27 years of age were included. Frequency of opportunistic vaccination, overall and by birth cohort, was calculated; screening outcomes were compared between vaccinated and unvaccinated women. Results: Overall, 4718 (4.9%) HPV-vaccinated, and 91,512 unvaccinated, women were studied. The frequency of vaccination increased by birth cohort, ranging between 1.8% and 9.8%; age at vaccination decreased progressively by birth cohort (p < 0.0001). Participation in screening was 60.8% among vaccinated, and 56.6% among unvaccinated, women (p < 0.0001). Detection rates (DR) for high-grade lesions were lower in vaccinated women (2.11‰ vs. 3.85‰ in unvaccinated, for CIN3+, p = 0.24; 0.0‰ vs. 0.22‰ for cancer). The DR of CIN3+ increased with age at vaccination, scoring respectively 0.0‰, 0.83‰, and 4.68‰ for women vaccinated when they were 15–16, 17–20, and 21–25 years old (p = 0.17). Conclusions: In comparison to unvaccinated women, higher compliance with cervical cancer screening invitation and lower CIN3+ DR among vaccinated women was observed. Age at vaccination was inversely correlated to vaccination efficacy. Full article
(This article belongs to the Special Issue HPV and HPV Vaccine)
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14 pages, 2397 KiB  
Article
Distribution of Human Papillomavirus (HPV) Genotypes in HIV-Negative and HIV-Positive Women with Cervical Intraepithelial Lesions in the Eastern Cape Province, South Africa
by Ongeziwe Taku, Zizipho Z. A. Mbulawa, Keletso Phohlo, Mirta Garcia-Jardon, Charles B. Businge and Anna-Lise Williamson
Viruses 2021, 13(2), 280; https://0-doi-org.brum.beds.ac.uk/10.3390/v13020280 - 11 Feb 2021
Cited by 16 | Viewed by 2862
Abstract
South African women have a high rate of cervical cancer cases, but there are limited data on human papillomavirus (HPV) genotypes in cervical intraepithelial neoplasia (CIN) in the Eastern Cape province, South Africa. A total of 193 cervical specimens with confirmed CIN from [...] Read more.
South African women have a high rate of cervical cancer cases, but there are limited data on human papillomavirus (HPV) genotypes in cervical intraepithelial neoplasia (CIN) in the Eastern Cape province, South Africa. A total of 193 cervical specimens with confirmed CIN from women aged 18 years or older, recruited from a referral hospital, were tested for HPV infection. The cervical specimens, smeared onto FTA cards, were screened for 36 HPV types using an HPV direct flow kit. HPV prevalence was 93.5% (43/46) in CIN2 and 96.6% (142/147) in CIN3. HIV-positive women had a significantly higher HPV prevalence than HIV-negative women (98.0% vs. 89.1%, p = 0.012). The prevalence of multiple types was significantly higher in HIV-positive than HIV-negative women (p = 0.034). The frequently detected genotypes were HPV35 (23.9%), HPV58 (23.9%), HPV45 (19.6%), and HPV16 (17.3%) in CIN2 cases, while in CIN3, HPV35 (22.5%), HPV16 (21.8%), HPV33 (15.6%), and HPV58 (14.3%) were the most common identified HPV types, independent of HIV status. The prevalence of HPV types targeted by the nonavalent HPV vaccine was 60.9% and 68.7% among women with CIN2 and CIN3, respectively, indicating that vaccination would have an impact both in HIV-negative and HIV-positive South African women, although it will not provide full protection in preventing HPV infection and cervical cancer lesions. Full article
(This article belongs to the Special Issue HPV and HPV Vaccine)
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Review

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12 pages, 1203 KiB  
Review
The Reservoir of Persistent Human Papillomavirus Infection; Strategies for Elimination Using Anti-Viral Therapies
by Ke Zheng, Nagayasu Egawa, Aslam Shiraz, Mayako Katakuse, Maki Okamura, Heather M. Griffin and John Doorbar
Viruses 2022, 14(2), 214; https://0-doi-org.brum.beds.ac.uk/10.3390/v14020214 - 22 Jan 2022
Cited by 12 | Viewed by 5052
Abstract
Human Papillomaviruses have co-evolved with their human host, with each of the over 200 known HPV types infecting distinct epithelial niches to cause diverse disease pathologies. Despite the success of prophylactic vaccines in preventing high-risk HPV infection, the development of HPV anti-viral therapies [...] Read more.
Human Papillomaviruses have co-evolved with their human host, with each of the over 200 known HPV types infecting distinct epithelial niches to cause diverse disease pathologies. Despite the success of prophylactic vaccines in preventing high-risk HPV infection, the development of HPV anti-viral therapies has been hampered by the lack of enzymatic viral functions, and by difficulties in translating the results of in vitro experiments into clinically useful treatment regimes. In this review, we discuss recent advances in anti-HPV drug development, and highlight the importance of understanding persistent HPV infections for future anti-viral design. In the infected epithelial basal layer, HPV genomes are maintained at a very low copy number, with only limited viral gene expression; factors which allow them to hide from the host immune system. However, HPV gene expression confers an elevated proliferative potential, a delayed commitment to differentiation, and preferential persistence of the infected cell in the epithelial basal layer, when compared to their uninfected neighbours. To a large extent, this is driven by the viral E6 protein, which functions in the HPV life cycle as a modulator of epithelial homeostasis. By targeting HPV gene products involved in the maintenance of the viral reservoir, there appears to be new opportunities for the control or elimination of chronic HPV infections. Full article
(This article belongs to the Special Issue HPV and HPV Vaccine)
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36 pages, 4403 KiB  
Review
The Not-So-Good, the Bad and the Ugly: HPV E5, E6 and E7 Oncoproteins in the Orchestration of Carcinogenesis
by Om Basukala and Lawrence Banks
Viruses 2021, 13(10), 1892; https://0-doi-org.brum.beds.ac.uk/10.3390/v13101892 - 22 Sep 2021
Cited by 42 | Viewed by 5631
Abstract
Infection with HPV starts with the access of the viral particles to basal cells in the epidermis, potentially via microtraumas to the skin. The basal cells are able to keep away these pathogens in normal circumstances through a robust immune response from the [...] Read more.
Infection with HPV starts with the access of the viral particles to basal cells in the epidermis, potentially via microtraumas to the skin. The basal cells are able to keep away these pathogens in normal circumstances through a robust immune response from the host, as HPV infections are, in general, cleared within 2 to 3 weeks. However, the rare instances of persistent infection and/or in cases where the host immune system is compromised are major risk factors for the development of lesions potentially leading to malignancy. Evolutionarily, obligatory pathogens such as HPVs would not be expected to risk exposing the host to lethal cancer, as this would entail challenging their own life cycle, but infection with these viruses is highly correlated with cancer and malignancy—as in cancer of the cervix, which is almost always associated with these viruses. Despite this key associative cause and the availability of very effective vaccines against these viruses, therapeutic interventions against HPV-induced cancers are still a challenge, indicating the need for focused translational research. In this review, we will consider the key roles that the viral proteins play in driving the host cells to carcinogenesis, mainly focusing on events orchestrated by early proteins E5, E6 and E7—the not-so-good, the bad and the ugly—and discuss and summarize the major events that lead to these viruses mechanistically corrupting cellular homeostasis, giving rise to cancer and malignancy. Full article
(This article belongs to the Special Issue HPV and HPV Vaccine)
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12 pages, 230 KiB  
Review
De-Escalating Strategies in HPV-Associated Head and Neck Squamous Cell Carcinoma
by Panagiota Economopoulou, Ioannis Kotsantis and Amanda Psyrri
Viruses 2021, 13(9), 1787; https://0-doi-org.brum.beds.ac.uk/10.3390/v13091787 - 08 Sep 2021
Cited by 10 | Viewed by 2136
Abstract
HPV-related head and neck squamous cell carcinoma (HNSCC) has emerged as a diverse clinical and biological disease entity, mainly in young patients with oropharyngeal tumors who are nonsmokers and nondrinkers. Indeed, during the past few years, the pendulum has shifted towards a new [...] Read more.
HPV-related head and neck squamous cell carcinoma (HNSCC) has emerged as a diverse clinical and biological disease entity, mainly in young patients with oropharyngeal tumors who are nonsmokers and nondrinkers. Indeed, during the past few years, the pendulum has shifted towards a new epidemiological reality, the “HPV pandemic”, where the majority of oropharyngeal squamous cell carcinomas (OPSCCs) are attributed to HPV. The oncogenic potential of the virus is associated to its capacity of integrating oncogenes E6 and E7 into the host cell, leading to the inactivation of several tumor suppressor genes, such as Rb. HPV status can affect prognosis in OPSCC, but its role as a predictive biomarker remains to be elucidated. Given the favorable prognosis associated with HPV-positive disease, the concept of de-escalation treatment strategies has been developed with the primary intent being the reduction of treatment-related long-term toxicities. In this review, we aim to depict current data regarding treatment de-escalation in HPV-associated OPSCC and discuss ongoing clinical trials. Full article
(This article belongs to the Special Issue HPV and HPV Vaccine)
11 pages, 8626 KiB  
Review
Focus on HPV Infection and the Molecular Mechanisms of Oral Carcinogenesis
by Luigi Santacroce, Michele Di Cosola, Lucrezia Bottalico, Skender Topi, Ioannis Alexandros Charitos, Andrea Ballini, Francesco Inchingolo, Angela Pia Cazzolla and Gianna Dipalma
Viruses 2021, 13(4), 559; https://0-doi-org.brum.beds.ac.uk/10.3390/v13040559 - 26 Mar 2021
Cited by 42 | Viewed by 3647
Abstract
This study is focused on the epidemiological characteristics and biomolecular mechanisms that lead to the development of precancerous and cancerous conditions of oral lesions related to Human Papilloma Virus (HPV) infections. Current evidence from the literature demonstrates the role of HPV in potentially [...] Read more.
This study is focused on the epidemiological characteristics and biomolecular mechanisms that lead to the development of precancerous and cancerous conditions of oral lesions related to Human Papilloma Virus (HPV) infections. Current evidence from the literature demonstrates the role of HPV in potentially malignant oral disorders. Therefore, the underlying biomolecular processes can give arise, or contribute to, benign lesions as well as to oral carcinogenesis. Full article
(This article belongs to the Special Issue HPV and HPV Vaccine)
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20 pages, 3112 KiB  
Review
Potential Effects of Human Papillomavirus Type Substitution, Superinfection Exclusion and Latency on the Efficacy of the Current L1 Prophylactic Vaccines
by Ian N. Hampson, Anthony W. Oliver and Lynne Hampson
Viruses 2021, 13(1), 22; https://0-doi-org.brum.beds.ac.uk/10.3390/v13010022 - 24 Dec 2020
Cited by 8 | Viewed by 5932
Abstract
There are >200 different types of human papilloma virus (HPV) of which >51 infect genital epithelium, with ~14 of these classed as high-risk being more commonly associated with cervical cancer. During development of the disease, high-risk types have an increased tendency to develop [...] Read more.
There are >200 different types of human papilloma virus (HPV) of which >51 infect genital epithelium, with ~14 of these classed as high-risk being more commonly associated with cervical cancer. During development of the disease, high-risk types have an increased tendency to develop a truncated non-replicative life cycle, whereas low-risk, non-cancer-associated HPV types are either asymptomatic or cause benign lesions completing their full replicative life cycle. HPVs can also be present as non-replicative so-called “latent” infections and they can also show superinfection exclusion, where cells with pre-existing infections with one type cannot be infected with a different HPV type. Thus, the HPV repertoire and replication status present in an individual can form a complex dynamic meta-community which changes with respect to both time and exposure to different HPV types. In light of these considerations, it is not clear how current prophylactic HPV vaccines will affect this system and the potential for iatrogenic outcomes is discussed in light of recent outcome data. Full article
(This article belongs to the Special Issue HPV and HPV Vaccine)
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Other

8 pages, 7998 KiB  
Case Report
Leptomeningeal Carcinomatosis of a Poorly Differentiated Cervical Carcinoma Caused by Human Papillomavirus Type 18
by Pierpaolo Zorzato, Mattia Zambon, Silvia Gori, Helena Frayle, Maria Teresa Gervasi and Annarosa Del Mistro
Viruses 2021, 13(2), 307; https://0-doi-org.brum.beds.ac.uk/10.3390/v13020307 - 16 Feb 2021
Cited by 2 | Viewed by 1701
Abstract
Cervical cancer is caused by a persistent infection with high-risk types of Papillomaviruses (hrHPV); HPV16 and HPV18 are associated with about 70% of the cases. In the last decades the introduction of a cervical cancer screening has allowed a decrease in cervical cancer [...] Read more.
Cervical cancer is caused by a persistent infection with high-risk types of Papillomaviruses (hrHPV); HPV16 and HPV18 are associated with about 70% of the cases. In the last decades the introduction of a cervical cancer screening has allowed a decrease in cervical cancer incidence and mortality; regular adhesion to the screening procedures, by pap test or HPV test, and colposcopy, according to the international guidelines, prevents cancer development and allows for diagnosis at the early stages. Nowadays, in industrialized countries, it is not common to diagnose this pathology in advanced stages, and this occurrence is frequently associated with patient’s unattendance of cervical screening programs. We describe a case of delayed diagnosis of cervical cancer, posed only after the onset of the neurological symptoms caused by leptomeningeal metastases, despite a two-year history of abnormal cytology. The endocervical mass was analyzed by immunohistochemistry, and search and typing of HPV sequences was performed by PCR in the meningeal carcinomatous cells. A poorly differentiated squamous cell carcinoma was diagnosed, and HPV18 sequences were detected. This rapidly fatal case highlights the importance of following the evidence-based recommended protocols and the preventive role of the population-based cervical cancer screening programs. Full article
(This article belongs to the Special Issue HPV and HPV Vaccine)
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