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Advances in HPV-Associated Cancers of Different Organs
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Advances in HPV-Associated Cancers of Different Organs

A special issue of Cancers (ISSN 2072-6694). This special issue belongs to the section "Infectious Agents and Cancer".

Deadline for manuscript submissions: closed (15 September 2024) | Viewed by 5944

Special Issue Information

Dear Colleagues,

The relationship between persistent infections of oncogenic HPV genotypes and human carcinogenesis has been intensely studied since the late 1970s, when the role of HPV in cervical carcinogenesis was first suggested by zur Hausen. During the past few decades, remarkable progress has been made in basic research, unveiling the role of viral genes that interfere with the molecular signaling pathways of the host cells that, over the years, lead to the development of a malignant phenotype. Cancer of the uterine cervix was the first target of these studies, revealing important details of the cellular immortalization process. Better understanding of the role of HPV in cervical carcinogenesis also allowed the introduction and rational combination of different screening strategies (cytology, HPV testing and biomarkers), resulting in the production and global implementation of highly effective prophylactic HPV vaccines for the primary prevention of HPV-associated cancers. Following the analogy of HPV association with cervical cancer, other anatomic sites with similar malignancies (squamous cell cancer) have been studied as potential  sites of HPV-associated cancers since the early 1980s. Of these extra-genital sites, the upper respiratory tract was the first to be explored, covering oral mucosa, sino-nasal mucosa, larynx, and bronchus. Concomitantly, the first evidence of HPV involvement in benign and malignant lesions in the esophagus was obtained. Subsequently, several other malignancies have also been examined for their potential HPV association, including cancer of the breast and urinary bladder. The causal role of HPV in some of these extra-genital cancers has been generally accepted, e.g. cancers of the head and neck, whereas in some other cancers, the data are still incomplete or controversial. In this Special Issue of Cancers, a mixture of topics is covered, introducing some firmly accepted basic biology concepts, in addition to other topics that are more controversial or not yet firmly established.

Prof. Dr. Adhemar Longatto-Filho
Prof. Dr. Kari Syrjanen
Guest Editors

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. Cancers is an international peer-reviewed open access semimonthly 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 2900 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 carcinogenesis
  • human papillomavirus
  • HPV-related cancers
  • HPV biology
  • HPV vaccine

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Published Papers (4 papers)

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Research

19 pages, 8666 KiB  
Article
Comprehensive Transcriptome Analysis Reveals the Distinct Gene Expression Patterns of Tumor Microenvironment in HPV-Associated and HPV-Non Associated Tonsillar Squamous Cell Carcinoma
by Reham M. Alahmadi, Najat Marraiki, Mohammed Alswayyed, Hatim A. Khoja, Abdullah E. Al-Anazi, Rawan M. Alahmadi, Meshael M. Alkusayer, Bandar Alosaimi and Maaweya Awadalla
Cancers 2023, 15(23), 5548; https://doi.org/10.3390/cancers15235548 - 23 Nov 2023
Viewed by 1699
Abstract
Head and neck squamous cell carcinomas (HNSCCs) are a common type of cancer, ranking as the sixth most prevalent cancer worldwide and having a high morbidity and mortality rate. Among oropharyngeal squamous cell carcinoma (OPSCC) cancers, tonsillar squamous cell carcinoma (TSCC) is the [...] Read more.
Head and neck squamous cell carcinomas (HNSCCs) are a common type of cancer, ranking as the sixth most prevalent cancer worldwide and having a high morbidity and mortality rate. Among oropharyngeal squamous cell carcinoma (OPSCC) cancers, tonsillar squamous cell carcinoma (TSCC) is the most prevalent and has a particularly aggressive clinical course with poor disease outcomes. The tumor microenvironment (TME) of HNSCC is complex and heterogeneous, playing a crucial role in effective cancer therapy. Understanding the interaction between cancer inflammation, immunity, oncogenes, and tumor suppressor genes is essential for developing effective cancer treatments. This study aimed to gain a comprehensive understanding of the transcriptomes of the TME in TSCC, both associated with human papillomavirus (HPV) and not associated with HPV. The gene expression profiles of 168 genes linked to various cellular mediators and factors involved in inflammation, immunity crosstalk, transcription, signal transduction, oncogenesis, tumor suppression, angiogenesis, and apoptosis were analyzed. We identified 40 differentially expressed genes related to the communication between tumor cells and the cellular mediators of inflammation and immunity crosstalk. In HPV-positive TSCC patients, 33 genes were over-expressed with a fold change greater than 1.5, and 26 of these genes were unique to this group. In contrast, HPV-negative TSCC patients had 11 up-regulated genes. The results further showed that 48 gene transcripts related to oncogenesis, tumor suppression, angiogenesis, and apoptosis were up-regulated in both HPV-positive and HPV-negative TSCC patients. Among the HPV-positive TSCC patients, 37 genes were over-expressed, while the HPV-negative TSCC patients had 11 up-regulated genes. The tumor microenvironment (TME) of HPV-associated and HPV-non-associated TSCC exhibited distinct characteristics, including the dysregulation of various genes involved in cellular mediators, inflammation, immunity crosstalk, transcription factors, immune signaling pathways, signal transduction, oncogenesis, tumor suppression, angiogenesis, and apoptosis. Additionally, we detected six Hr-HPV genotypes in 81% of the TSCC patients, with HPV-16 and HPV-35 being the most common types, followed by HPV-45 and HPV-18. HPV-39 and 31 were also identified. The presence of Hr-HPV genotypes in TSCC patients varied from single to multiple infections. In conclusion, we observed distinct heterogeneity in the transcriptome of the microenvironment in HPV-associated and non-associated TSCC. Further in vitro and in vivo studies are needed to investigate the functional implications of the identified over-expressed genes. Also, deeper molecular pathways and immunological studies on the TME are required to determine the potential of targeting genes for cancer therapy. Full article
(This article belongs to the Special Issue Advances in HPV-Associated Cancers of Different Organs)
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22 pages, 5015 KiB  
Article
Unveiling the Association between HPV and Pan-Cancers: A Bidirectional Two-Sample Mendelian Randomization Study
by Jianxuan Sun, Jiacheng Xiang, Ye An, Jinzhou Xu, Yifan Xiong, Shaogang Wang and Qidong Xia
Cancers 2023, 15(21), 5147; https://doi.org/10.3390/cancers15215147 - 26 Oct 2023
Cited by 8 | Viewed by 3395
Abstract
Introduction: More and more studies have focused on the associations between human papillomavirus (HPV) infection and pan-cancers. However, current evidence is largely based on retrospective studies, which are susceptible to confounding factors and do not enable the establishment of causal relationships. Methods: A [...] Read more.
Introduction: More and more studies have focused on the associations between human papillomavirus (HPV) infection and pan-cancers. However, current evidence is largely based on retrospective studies, which are susceptible to confounding factors and do not enable the establishment of causal relationships. Methods: A bidirectional two-sample Mendelian randomization (MR) design was employed to thoroughly evaluate the causal relationships between HPV and 12 site-specific cancers except cervical cancer. Single nucleoside polymers (SNPs) with strong evidence from genome-wide association studies (GWAS) were selected from HPV exposure datasets and used as instrumental variables (IVs) in this study. For the MR analysis results, MR-Egger’s intercept P test, MR-PRESSO global test, Cochran’s Q test and a leave-one-out test were applied for sensitivity analysis. Using HPVTIMER, we also performed immune infiltration analyses in head and neck squamous cell carcinoma (HNSCC), oropharyngeal squamous cell carcinoma (OPSCC) and vulval squamous cell carcinoma (VSCC) to evaluate the tumor-immune microenvironment. Results: Based on the evidence of MR analysis, our study conclusively identified HPV16 as a risk factor implicated in the development of bladder cancer, colorectal cancer, and breast cancer, while HPV18 was identified as a risk factor for prostate cancer, ovarian cancer, lung cancer and breast cancer. The MR results also showed that HPV16 may be a protective factor for prostate cancer, anal cancer, lung cancer and oropharyngeal cancer, while HPV18 may be a protective factor for vaginal cancer. Conclusion: An HPV infection may modulate the immune microenvironment and therefore has a potential inhibitory effect on the development of certain cancers. These conclusions provided new insights into the potential mechanisms of carcinogenesis and needed further research for validation. Full article
(This article belongs to the Special Issue Advances in HPV-Associated Cancers of Different Organs)
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13 pages, 1438 KiB  
Article
Predictors for Survival of Patients with Squamous Cell Carcinoma of Unknown Primary in the Head and Neck Region
by Steffen Wagner, Christine Langer, Nora Wuerdemann, Susanne Reiser, Helen Abing, Jörn Pons-Kühnemann, Elena-Sophie Prigge, Magnus von Knebel Doeberitz, Stefan Gattenlöhner, Tim Waterboer, Lea Schroeder, Christoph Arens, Jens Peter Klussmann and Claus Wittekindt
Cancers 2023, 15(7), 2167; https://doi.org/10.3390/cancers15072167 - 6 Apr 2023
Cited by 3 | Viewed by 2060
Abstract
Background: Human papillomavirus (HPV) status is the most important predictor of survival in oropharyngeal squamous cell carcinoma (OPSCC). In patients with cervical lymph node metastases of squamous cell carcinoma of unknown origin (CUPHNSCC), much less is known. Methods: We assessed a [...] Read more.
Background: Human papillomavirus (HPV) status is the most important predictor of survival in oropharyngeal squamous cell carcinoma (OPSCC). In patients with cervical lymph node metastases of squamous cell carcinoma of unknown origin (CUPHNSCC), much less is known. Methods: We assessed a consecutive cohort of CUPHNSCC diagnosed from 2000–2018 for HPV DNA, mRNA, p16INK4a (p16) expression, and risk factors to identify prognostic classification markers. Results: In 32/103 (31%) CUPHNSCC, p16 was overexpressed, and high-risk HPV DNA was detected in 18/32 (56.3%). This was mostly consistent with mRNA detection. In recursive partitioning analysis, CUPHNSCC patients were classified into three risk groups according to performance status (ECOG) and p16. Principal component analysis suggests a negative correlation of p16, HPV DNA, and gender in relation to ECOG, as well as a correlation between N stage, extranodal extension, and tobacco/alcohol consumption. Conclusions: Despite obvious differences, CUPHNSCC shares similarities in risk profile with OPSCC. However, the detection of p16 alone appears to be more suitable for the classification of CUPHNSCC than for OPSCC and, in combination with ECOG, allows stratification into three risk groups. In the future, additional factors besides p16 and ECOG may become important in larger studies or cases with special risk profiles. Full article
(This article belongs to the Special Issue Advances in HPV-Associated Cancers of Different Organs)
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13 pages, 2806 KiB  
Article
HPV Type Distribution in Benign, High-Grade Squamous Intraepithelial Lesions and Squamous Cell Cancers of the Anus by HIV Status
by Sona Chowdhury, Teresa M. Darragh, J. Michael Berry-Lawhorn, Maria G. Isaguliants, Maxim S. Vonsky, Joan F. Hilton, Ann A. Lazar and Joel M. Palefsky
Cancers 2023, 15(3), 660; https://doi.org/10.3390/cancers15030660 - 20 Jan 2023
Cited by 4 | Viewed by 2180
Abstract
The incidence of anal cancer is increasing, especially in high-risk groups, such as PLWH. HPV 16, a high-risk (HR) HPV genotype, is the most common genotype in anal high-grade squamous intraepithelial lesions (HSIL) and squamous cell carcinoma (SCC) in the general population. However, [...] Read more.
The incidence of anal cancer is increasing, especially in high-risk groups, such as PLWH. HPV 16, a high-risk (HR) HPV genotype, is the most common genotype in anal high-grade squamous intraepithelial lesions (HSIL) and squamous cell carcinoma (SCC) in the general population. However, few studies have described the distribution of HR HPV genotypes other than HPV 16 in the anus of PLWH. HPV genotyping was performed by DNA amplification followed by dot-blot hybridization to identify the HR and low-risk (LR) genotypes in benign anal lesions (n = 34), HSIL (n = 30), and SCC (n = 51) of PLWH and HIV-negative individuals. HPV 16 was the most prominent HR HPV identified, but it was less common in HSIL and SCC from PLWH compared with HIV-negative individuals, and other non-HPV 16 HR HPV (non-16 HR HPV) types were more prevalent in samples from PLWH. A higher proportion of clinically normal tissues from PLWH were positive for one or more HPV genotypes. Multiple HPV infection was a hallmark feature for all tissues (benign, HSIL, SCC) of PLWH. These results indicate that the development of anal screening approaches based on HPV DNA testing need to include non-16 HR HPVs along with HPV 16, especially for PLWH. Along with anal cytology, these updated screening approaches may help to identify and prevent anal disease progression in PLWH. Full article
(This article belongs to the Special Issue Advances in HPV-Associated Cancers of Different Organs)
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