Updates on Human Papillomavirus Induced Neoplasms

A special issue of Microorganisms (ISSN 2076-2607). This special issue belongs to the section "Medical Microbiology".

Deadline for manuscript submissions: closed (31 December 2020) | Viewed by 23468

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Faculty of Health Sciences, Kanazawa University, 5-11-80 Kodatsuno, Kanazawa, Ishikawa 920-0942, Japan
Interests: hematology and oncology; microbe-induced carcinogenesis; cancer drug discovery; parasitic infections; opportunistic microorganisms; immunology; microbiota; infectious diseases; artificial intelligence and medical sciences
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Dear Colleagues,

HPV is still the most frequent sexually transmitted pathogens worldwide. Although a majority of infections are asymptomatic and in most cases the virus becomes undetectable within two years of exposure, persistent infections with carcinogenic types of HPV can result in the development of cervical cancer and other HPV-associated malignancies such as vaginal, vulvar, penile, and anal cancers, as well as nasopharyngeal cancers. The identification of risk factors that can increase the probability of developing persistent HPV infections in certain populations has been an important topic of research, and accumulating evidence indicates that genetic and lifestyle factors, and likely co-infection with other microorganisms may, at least in part, interfere with the ability of the host immune system to achieve an effective “viral clearance”.

Cervical cancer screening programs based on cytological and/or detection of HPV DNA, HPV mRNA, or other viral markers have contributed to a dramatic decline in the incidence and mortality of cervical cancer in developed countries; however, current screening programs in low-income countries have failed to achieve a major impact on disease prevention. As a result, worldwide mortality of cervical cancer is about 300,000 cases each year, with nearly 90% of deaths occurring in developing countries.

The development and licensure of prophylactic HPV vaccines capable of eliciting effective immunity through the production of high titers of anti-HPV IgG neutralizing antibodies is increasing. These licensed vaccines are safe and highly effective against the most common oncogenic HPV types associated with cervical cancer and anogenital cancers, and are likely to prevent HPV+ oropharyngeal cancers; furthermore, HPV vaccination has significantly reduced the incidence of genital warts. However, coverage of HPV vaccines is a major limitation and is especially in low-income countries; HPV vaccines are not available through national immunization programs, and thus cost is a critical barrier for the delivery of HPV immunization in developing countries.

This Issue will highlight recent advances in the understating of HPV-induced neoplasms, with an emphasis on topics related to the diagnosis, prevention, and management of these disorders. We welcome the submission of original research articles encompassing both preclinical and clinical studies, as well as review and opinion articles dealing with but are not limited to the following: (1) new insights into HPV-induced carcinogenesis, (2) screening tools in HPV-associated cancers, (3) prophylactic and therapeutic vaccines in HPV-induced cancers, (4) the impact of co-infection with other microorganisms in HPV-induced cancers, (5) microbiota and HPV infection, (6) utilization of artificial intelligence tools for the diagnosis and management of HPV-associated neoplasms, (7) the application of new-generation sequencing for understanding HPV-induced cancers, (8) new antiviral agents for the eradication of HPV infection, (8) studies elucidating the natural history of HPV infection, and (9) biosimilar HPV vaccines.

We would welcome the direct submission of original research that meets the above criteria—please submit directly via MDPI Microorganisms, stating in your cover letter that you are targeting this Special Issue, or email your pre-submission queries if you are not sure about the suitability of your work.

Dr. Jorge Luis Espinoza
Guest Editor

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Published Papers (5 papers)

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Research

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11 pages, 592 KiB  
Article
Human Papillomavirus Distribution in Women with Abnormal Pap Smear and/or Cervical Intraepithelial Neoplasia in Vaccination Era. A Single-Center Study in the North Italian Population
by Barbara Gardella, Mattia Dominoni, Cecilia Sosso, Anna Arrigo, Andrea Gritti, Stefania Cesari, Giacomo Fiandrino and Arsenio Spinillo
Microorganisms 2021, 9(4), 729; https://doi.org/10.3390/microorganisms9040729 - 31 Mar 2021
Cited by 5 | Viewed by 2404
Abstract
Time trends prevalence of human papillomavirus (HPV) genotypes including negative and untypable infections were analyzed during a 15-year period (2005–2019) among 5807 subjects with abnormal pap-smears and/or cervical intraepithelial neoplasia (CIN). The rates of HPV16 dropped by 13% every 3 years (Prevalence Ratio, [...] Read more.
Time trends prevalence of human papillomavirus (HPV) genotypes including negative and untypable infections were analyzed during a 15-year period (2005–2019) among 5807 subjects with abnormal pap-smears and/or cervical intraepithelial neoplasia (CIN). The rates of HPV16 dropped by 13% every 3 years (Prevalence Ratio, PR = 0.87, 95% CI = 0.82–0.93) in the CIN1 biopsy, while HPV16 status was unchanged over time in the CIN2+ biopsy. In CIN1 lesions, there was a corresponding increase of HR-HPV types unrelated to nonavalent vaccine. The rates of HPV 18, 31, and 52, decreased by 35% (PR = 0.65, 95% CI = 0.54–0.79), 19% (PR = 0.81, 95% CI = 0.73–0.91), and 21% (PR = 0.79, 95% CI = 0.73–0.86) every 3-year interval in CIN2+, respectively. Overall, the prevalence of negative/untypable HPV specimens in the entire database increased from 9.6% (129/1349) in the period 2011–2013 to 17.6% (161/913) and 28.4% (224/790) in the 2014–2016 period and in the 2017–2019 period, respectively (PR = 1.69, 95% CI = 1.52–1.88). HPV 16 prevalence decreased significantly among subjects with low-grade cervical squamous lesions. A significant increase of both HPV types unrelated to nonavalent vaccination and negative/untypable HPV infections was reported. The prevalence of HPV types among subjects with abnormal pap smears in Northern Italy is changing. Many variables including demographic factors and possibly vaccination could be responsible for this modification. Full article
(This article belongs to the Special Issue Updates on Human Papillomavirus Induced Neoplasms)
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12 pages, 835 KiB  
Article
Evolving Profile of HPV-Driven Oropharyngeal Squamous Cell Carcinoma in a National Cancer Institute in Italy: A 10-Year Retrospective Study
by Maria Gabriella Donà, Francesca Rollo, Barbara Pichi, Giuseppe Spriano, Silvia Moretto, Renato Covello, Raul Pellini and Maria Benevolo
Microorganisms 2020, 8(10), 1498; https://doi.org/10.3390/microorganisms8101498 - 29 Sep 2020
Cited by 20 | Viewed by 2082
Abstract
Globally, 30% of oropharyngeal carcinomas (OPSCC) are caused by Human Papillomavirus (HPV). Recently, increasing incidence trends for HPV-driven OPSCC have been reported in many countries and changes in the typical HPV-positive OPSCC patient have been recorded, with an increase in the median age [...] Read more.
Globally, 30% of oropharyngeal carcinomas (OPSCC) are caused by Human Papillomavirus (HPV). Recently, increasing incidence trends for HPV-driven OPSCC have been reported in many countries and changes in the typical HPV-positive OPSCC patient have been recorded, with an increase in the median age and diagnoses in women. We investigated the characteristics of the OPSCC patients attending an Italian Cancer Institute from 2010 to 2019 and assessed possible changes overtime of demographic, behavioral, and clinico-pathologic variables of HPV-driven OPSCC. Overall, 339 OPSCCs were evaluated. HPV-DNA and p16 positivity were 48.7% and 55.2%, respectively, with an HPV-driven fraction (i.e., HPV-DNA+/p16+) of 48.3%. We observed a significant increase overtime in the rate of HPV-associated cases (53.7% in 2015–2019 vs. 40.3% in 2010–2014, p = 0.019). The rate of HPV-driven cases was significantly higher among women, never smokers, patients with T1–T2 tumors, and with nodal involvement. A trend was also observed toward an increase in HPV-driven OPSCCs among patients >61 years, women, former smokers, and patients with no nodal involvement in 2015–2019. Our findings consolidate the observation that HPV-associated OPSCCs are also increasing in Italy. Moreover, they suggest that the profile of the HPV-driven OPSCC patient might be changing. Full article
(This article belongs to the Special Issue Updates on Human Papillomavirus Induced Neoplasms)
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Review

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23 pages, 975 KiB  
Review
Genetic Predisposition to Persistent Human Papillomavirus-Infection and Virus-Induced Cancers
by Helen Espinoza, Kim T. Ha, Trang T. Pham and J. Luis Espinoza
Microorganisms 2021, 9(10), 2092; https://doi.org/10.3390/microorganisms9102092 - 3 Oct 2021
Cited by 19 | Viewed by 5095
Abstract
Human papillomaviruses (HPVs) are the most common sexually transmitted pathogens worldwide and among the more than 200 identified HPV types, approximately 15 high risk (HR-HPV) types are oncogenic, being strongly associated with the development of cervical cancer, anogenital cancers and an increasing fraction [...] Read more.
Human papillomaviruses (HPVs) are the most common sexually transmitted pathogens worldwide and among the more than 200 identified HPV types, approximately 15 high risk (HR-HPV) types are oncogenic, being strongly associated with the development of cervical cancer, anogenital cancers and an increasing fraction of head and neck squamous cell carcinomas (HNSCC). HPV-associated cervix cancer accounts for 83% of HPV-attributable cancers, and more than two-thirds of those cases occur in developing countries. Despite the high frequency of HPV infections, in most cases, the virus is cleared by the host immune response and only a small proportion of infected individuals develop persistent infections that can result in malignant transformation, indicating that other elements, including biological, genetic and environmental factors may influence the individual susceptibility to HPV-associated cancers. Previous studies have quantified that heritability, in the form of genetic variants, common in the general population, is implicated in nearly 30% of cervical cancers and a large number of studies conducted across various populations have identified genetic variants that appear to be associated with genes that predispose or protect the host to HPV infections thereby affecting individual susceptibility to HPV-associated cancers. In this article, we provide an overview of gene association studies on HPV-associated cancers with emphasis on genome-wide association study (GWAS) that have identified novel genetic factors linked to HPV infection or HPV-associated cancers. Full article
(This article belongs to the Special Issue Updates on Human Papillomavirus Induced Neoplasms)
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22 pages, 2322 KiB  
Review
The Host-Microbe Interplay in Human Papillomavirus-Induced Carcinogenesis
by Rei Wakabayashi, Yusuke Nakahama, Viet Nguyen and J. Luis Espinoza
Microorganisms 2019, 7(7), 199; https://doi.org/10.3390/microorganisms7070199 - 13 Jul 2019
Cited by 47 | Viewed by 9490
Abstract
Every year nearly half a million new cases of cervix cancer are diagnosed worldwide, making this malignancy the fourth commonest cancer in women. In 2018, more than 270,000 women died of cervix cancer globally with 85% of them being from developing countries. The [...] Read more.
Every year nearly half a million new cases of cervix cancer are diagnosed worldwide, making this malignancy the fourth commonest cancer in women. In 2018, more than 270,000 women died of cervix cancer globally with 85% of them being from developing countries. The majority of these cancers are caused by the infection with carcinogenic strains of human papillomavirus (HPV), which is also causally implicated in the development of other malignancies, including cancer of the anus, penis cancer and head and neck cancer. HPV is by far the most common sexually transmitted infection worldwide, however, most infected people do not develop cancer and do not even have a persistent infection. The development of highly effective HPV vaccines against most common high-risk HPV strains is a great medical achievement of the 21st century that could prevent up to 90% of cervix cancers. In this article, we review the current understanding of the balanced virus-host interaction that can lead to either virus elimination or the establishment of persistent infection and ultimately malignant transformation. We also highlight the influence of certain factors inherent to the host, including the immune status, genetic variants and the coexistence of other microbe infections and microbiome composition in the dynamic of HPV infection induced carcinogenesis. Full article
(This article belongs to the Special Issue Updates on Human Papillomavirus Induced Neoplasms)
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Other

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9 pages, 3470 KiB  
Case Report
Pathological and Virological Studies of p16-Positive Oropharyngeal Carcinoma with a Good Response to Neoadjuvant Chemotherapy
by Daisuke Inukai, Taichi Kan, Shunpei Yamanaka, Hiroki Okamoto, Yasushi Fujimoto, Takanori Ito, Natsuki Taniguchi, Yuuki Yamamoto, Toyonori Tsuzuki, Akiyoshi Takami and Tetsuya Ogawa
Microorganisms 2020, 8(10), 1497; https://doi.org/10.3390/microorganisms8101497 - 29 Sep 2020
Cited by 4 | Viewed by 3592
Abstract
Human papillomavirus (HPV)-related, p16-positive oropharyngeal carcinoma is considered to be sensitive to anticancer drugs, and the standard treatment is therefore chemoradiotherapy, rather than surgery, especially for aggressive disease. However, with this higher sensitivity, chemotherapy alone may achieve a pathological complete response (CR), making [...] Read more.
Human papillomavirus (HPV)-related, p16-positive oropharyngeal carcinoma is considered to be sensitive to anticancer drugs, and the standard treatment is therefore chemoradiotherapy, rather than surgery, especially for aggressive disease. However, with this higher sensitivity, chemotherapy alone may achieve a pathological complete response (CR), making radiation therapy unnecessary. A 46-year-old man with p16-positive squamous cell carcinoma (SCC) of the lateral oropharynx (palatine tonsil) underwent neoadjuvant chemotherapy. This achieved clinically significant tumor shrinkage and therefore surgery was performed for subsequent definitive treatment. Clinical and CT findings indicated a good effect of neoadjuvant chemotherapy on the tumor. A biopsy prior to chemotherapy revealed SCC, which demonstrated p16 immunoreactivity and positive signals for high-risk HPV by RNA in situ hybridization. The post-chemotherapy surgical specimen showed pathological CR and no p16 positive cells nor positive signals for high-risk HPV those were detected in the pre-chemotherapy specimen. There are some reports of chemotherapy alone achieving pathological CR in cases of p16-positive oropharyngeal carcinoma, but none have included high-risk HPV RNA findings. This is the first report of the disappearance of cancer cells as well as p16 staining and a positive signal for high-risk HPV. Achieving pathological CR confirmed by immunohistochemistry and high-risk HPV RNA in situ hybridization in a solid tumor with chemotherapy alone suggests that chemotherapy may have both an antitumor effect and an antiviral effect. Forgoing subsequent radiotherapy and undergoing surgery might be unnecessary and follow-up instead might be sufficient in such cases. Into the future, in an optimal tailored treatment approach, the option of neoadjuvant chemotherapy should be considered for management of p16-positive oropharyngeal carcinoma. Other options such as tumor immunotherapy are also expected to be effective. Full article
(This article belongs to the Special Issue Updates on Human Papillomavirus Induced Neoplasms)
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