Human Papillomavirus Involvement Research Articles

Human papillomavirus and endometrial cancer (review of literature and meta-analysis)

The important role of human papillomavirus (HPV) of high carcinogenic risk in the emergence and development of cervical cancer is undeniable. Approximately 90 % of cases of verified cervical cancer are HPV positive. The level of infection with this virus exceeds that of gonococci, chlamydia and yeast infections. Currently, one of the most discussed issues is the possibility of the association of HPV with the risk of developing malignant neoplasms when localized in organs that are anatomically close to the cervix. One of these localizations is the body of the uterus. It is known that endometrial cancer is based on its pronounced hormone dependence. Nevertheless, many factors are involved in the carcinogenesis of endometrial neoplasms, including genetic and epigenetic disorders, as well as risk factors, which include alimentary, hormonal, hereditary causes. At the same time, a controversial issue is the involvement of HPV in the development of this type of cancer. The data on the presence of HPV in endometrial cancer are extremely contradictory: the researchers claim both the complete absence of the effect of the virus on the development of this type of cancer, and the detection of HPV in 60–80 % of cases of tumors. In this regard, it becomes necessary to systematize the currently available research results on this issue and to conduct a meta-analysis of the association of HPV infection with the risk of endometrial cancer.

Conjunctival cancer in people living with HIV.

Historically, conjunctival cancer has been associated with HIV particularly in sub-Saharan Africa. The human papilloma virus (HPV) has been implicated as a potential causative agent without conclusive evidence. This review covers recent evidence of the epidemiology, diagnosis and treatment of conjunctival cancer in people living with HIV (PLWH). HIV infection has been attributed to 33% of squamous cell carcinoma of the conjunctiva in sub-Saharan Africa. Although clear evidence of the effect of immunodeficiency on conjunctival cancer risk has been demonstrated, the role of HPV on conjunctival cancer development is still unclear. Biomarkers such as the p16 protein are not always indicative of HPV infection. The Epstein-Barr virus (EBV) might potentially be another infectious agent of interest in the development of conjunctival cancer. There is some evidence of increased conjunctival cancer recurrence post treatment as well as increased probability of metastasis in PLWH. Immunodeficiency increases the risk of conjunctival cancer in PLWH. Symptomatic screening of conjunctival cancer in PLWH should be encouraged. Research on HPV involvement should remain a priority and EBV considered as another etiologic agent of interest. More studies on treatment modalities in PLWH should be considered.

Selected updates in molecular and genomic pathology of esophageal cancer.

Recent years have seen rapid advances in the field of molecular and genomic pathology that have not only improved understanding of esophageal carcinogenesis and tumor immune environment in general but also have reshaped pathology practice and clinical management. In this article, we provide updates on three topics (1) human epidermal growth factor receptor 2, the first and most important biomarker in targeted therapy of esophageal cancer; (2) programmed death 1/programmed death ligand 1, recent biomarkers that have shown promise in treating both esophageal adenocarcinoma and esophageal squamous cell carcinoma; and (3) human papillomavirus involvement in esophageal carcinogenesis, one of the most debated topics in the field, discussed here with a renewed understanding from recent genomic and molecular data.

Клиническая эффективность использования рекомбинантного интерферона α-2b в терапии мужского бесплодия, обусловленного вирусом папилломы человека

The involvement of human papillomavirus (HPV) in male infertility is becoming increasingly evident. There are no approved treatment for male infertility associated with human papillomavirus infection (HPV).To study the effectiveness of interferon therapy (recombinant interferon -2b with an antioxidant complex of vitamins E and C) in the treatment of male infertility associated with HPV MATERIALS AND METHODS: An analysis of the results of a survey of 103 patients aged 28 to 46 years with a diagnosis of infertility associated with HPV was carried out. Ejaculate was assessed in accordance with the WHO recommendations (2010); the amplification method of DNA diagnostics, polymerase chain reaction (PCR), was used to identify the type of virus. The material for the study was ejaculate. Depending on the therapy, the patients were divided into two groups: the 1st control group (n=54) - were under observation. Group 2 (n=49) - received treatment with recombinant interferon -2b with an antioxidant complex of vitamins E and C (Viferon), (rectal suppositories), which was prescribed at a dosage of 3,000,000 IU per rectum 2 times a day with an interval of 12 hours for 20 days. The observation period is 1 year. The end point of the study was the onset of pregnancy.When comparing the characteristics of the groups obtained, no statistically significant difference was found. Almost all of the studied patients had various types of pathospermia. When identifying the virus, 6, 16, 18, 31, 33 types of HPV were most often detected in the ejaculate. The most common disorder in the studied groups is asthenozoospermia. The association of several types of virus had a statistically significant weak inverse correlation with morphological changes in the ejaculate, in comparison with the ejaculate where one type of virus was detected (r=0.257, p=0.0853). The more types of the virus were registered in the ejaculate in associative relationships, the more the expression of morphological changes in the ejaculate.Male infertility may be due to the presence of HPV in the ejaculate. The more types of HPV present in the ejaculate, the lower the total sperm motility. For the treatment of infertility caused by PVI, it is recommended to use recombinant interferon -2b with an antioxidant complex of vitamins E and C.

Importance of investigating high-risk human papillomavirus in lymph node metastasis of esophageal adenocarcinoma.

High-risk human papillomavirus has been suggested as a risk factor for esophageal adenocarcinoma. Tumor human papillomavirus status has been reported to confer a favorable prognosis in esophageal adenocarcinoma. The size of the primary tumor and degree of lymphatic spread determines the prognosis of esophageal carcinomas. Lymph node status has been found to be a predictor of recurrent disease as well as 5-year survival in esophageal malignancies. In human papillomavirus driven cancers, e.g. cervical, anogenital, head and neck cancers, associated lymph nodes with a high viral load suggest metastatic lymph node involvement. Thus, human papillomavirus could potentially be useful as a marker of micro-metastases. To date, there have been no reported studies regarding human papillomavirus involvement in lymph nodes of metastatic esophageal adenocarcinoma. This review highlights the importance of investigating human papillomavirus in lymph node metastasis of esophageal adenocarcinoma based on data derived from other human papillomavirus driven cancers.

HPV Involvement in the Tumor Microenvironment and Immune Treatment in Head and Neck Squamous Cell Carcinomas.

Head and neck squamous cell carcinomas (HNSCC) are one of the most prevalent cancers worldwide. Active human papillomavirus (HPV) infection has been identified as an important additional risk factor and seems to be associated with a better prognosis in non-drinker and non-smoker young patients with oropharyngeal SCC. The better response of the immune system against the HPV-induced HNSCC is suspected as a potential explanation for the better prognosis of young patients. To further assess this hypothesis, our review aims to shed light the current knowledge about the impact of HPV infection on the immune response in the context of HNSCC, focusing on the innate immune system, particularly highlighting the role of macrophages, Langerhans and myeloid cells, and on the adaptative immune system, pointing out the involvement of T regulatory, T CD8 and T CD4 lymphocytes. In addition, we also review the preventive (HPV vaccines) and therapeutic (checkpoint inhibitors) strategies against HPV-related HNSCC, stressing the use of anti-CTLA4, PD-L1, PD-L2 antibodies alone and in combination with other agents able to modulate immune responses.

Morpholiogical, quantitative image analysis and molecular biology of oesophageal squamous cell carcinoma (ESCC), with special reference to tumour progression and human papillomavirus (HPV) involvement

It is an urgent need to improve early diagnosis of ESCC, because is one of the most aggressive cancer. The quantitative image analysis can aid in the identification of ESCC. Despite much research effort, the major prognostic factor of ESCC remains the pathological stage of the disease as defined by the TNM classification, whereas tumour grading is of limited value in this respect, mainly due to its low reproducibility. A better means for disease prognostication based on improved understanding of the pathogenetic mechanisms is urgently required. Materials and methods: The material of the present study was derived from a series of 1876 oesophageal surgical specimens taken from a total of 700 patients, who underwent oesophageal resection for an invasive ESCC in Anyang Tumour Hospital, Henan Province of China. Among. The cases of ESCC, previously subjected to extensive testing for Human Papillomavirus (HPV) involvement and expression of p53 gene. All cases are analysed by histopathology and by in situ hybridisation (ISH) and PCR, and a group of 272 patients was randomly selected for analysis of the primary tumour, adjacent mucosa and regional lymph nodes, in the quantitative image analysis. All cases and HPV data were subjected to extensive univariate and multivariate analysis to disclose independent predictors of progressive disease. Results: For the analyses, the ESCCs were graded into two categories: well – moderately and poorly-differentiated. HPV DNA was detected in 116 (18.9 %) of the carcinomas by ISH and in 15.2 % by PCR. In univariate analysis, lymph node status was significantly (p < 0.01) predicted by the following nuclear parameters: nuclear area, G0/G1 ratio, HPV DNA status, integrated optical density (IOD), mean optical density (MOD) and S-Phase. In multivariate analysis, 6 variables remained as independent predictors of disease progression (p < 0.05 level), the three most significant ones being nuclear perimeter, nuclear roundness and equivalent diameter (p < 0.01). Conclusions: A series of quantitatively measured nuclear parameters seem to be a close correlation with ESCC differentiation and progression in univariate analysis and some of these variables proved to be significant independent predictors of disease progression in multivariate modelling as well. These data clearly advocate the use of quantitative image analysis in searching for additional prognostic factors of ESCC.

Enhanced Radiation Sensitivity of Human Papillomavirus-Driven Head and Neck Cancer: Focus on Immunological Aspects.

Head and neck squamous cell carcinomas (HNSCC), emerging in the mucosa of the upper aerodigestive tract, are associated with either the classical risk factors, tobacco and alcohol consumption, or with infections with high-risk types of the human papillomavirus (HPV). Depending on the involvement of HPV, HNSCC follow different pathways of carcinogenesis and show distinct clinical presentations regarding survival, prognosis and treatment response. For instance, HPV-driven HNSCC exhibit an enhanced radiation response compared to their typically radioresistant HPV-negative counterparts. Although radiosensitivity of HNSCC has been studied by many research groups, the major causes for the difference in radiation responses between HPV-driven and HPV-negative HNSCC are still an open question. In this mini review, we discuss the reported cellular and immunological factors involved in the enhanced radiation response in HPV-driven HNSCC, focusing on the vital role of the immune response in the outcome of HNSCC radiotherapy.

P2.10-01 Analysis of Human Papilloma Viruses (HPV) and Human Polyoma Viruses (HPyV) in Lung Cancer from Swedish Never-Smokers

A possible role for oncogenic infections in the etiology of lung cancer has been investigated in a large number of studies, with contradictory results. High-risk mucosal human papillomaviruses (HPV), recognized as being associated with cervical cancer and oropharyngeal cancer, has been suggested as a causative factor also in lung cancer [1,2], whereas other studies found no, or at most very limited, involvement of HPV in lung cancer [3,4]. To investigate human papillomaviruses (HPV) and human polyomaviruses (HPyV) as possible causative factors behind lung cancer in never-smokers, we analyzed the presence of these viruses in a subset of tumors within a larger Swedish cohort of never-smoking lung cancer patients [Swedish Molecular Initiative against Lung cancer, SMIL; Salomonsson et al. Abstract WCLC 2019]. Eighty-seven surgically resected lung cancer samples from never-smokers, diagnosed 2005-2014 in Stockholm, Sweden, were analyzed by Luminex assays for the presence of 27 HPV types (including all HPV types currently regarded as high-risk types) and for 10 HPyV species (BKPyV, JCPyV, KIPyV, WUPyV, TSPyV, MWPyV, HPyV6, 7, 9, and 10). All samples were positive for the β-globin gene, confirming the presence, amplification and detection of cellular DNA. All samples were negative for the HPV types included in the assay. The only viral DNA detected in the tumors were low amounts of Merkel cell polyomavirus (MCPyV) DNA, of unknown significance, in 15 samples. Our study shows no evidence for neither HPV nor HPyV in the etiology of lung cancer in Swedish never-smokers.

Impact of HPV Infection on the Immune System in Oropharyngeal and Non-Oropharyngeal Squamous Cell Carcinoma: A Systematic Review.

Objectives: To review the current knowledge regarding the involvement of human papilloma virus (HPV) infection and the immune system in the development of head and neck squamous cell carcinoma (HNSCC). Methods: An electronic literature search was conducted to identify articles published between 1990 and 2019 pertaining to tumor-infiltrating immune cells (TICs) in HNSCC using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Issues of clinical relevance, including tumor location, the number of tumor samples, the inclusion of additional specimens (dysplastic or normal mucosa), tumor size, methods used for HPV detection, relationship between antigen expression and patient characteristics (age, gender, smoking, alcohol consumption, etc.), and prognostic data (overall survival (OS) and recurrence-free survival (RFS)) were assessed by four blinded investigators. Results: The search identified 335 relevant studies, of which 41 met the inclusion criteria. Of these, 7 studies focused on the peripheral blood immune cell concentration in patients with HNSCC according to HPV status, and 36 studies investigated TICs in the intraepithelial and/or stromal compartment(s) according to HPV status. The immune cells studied were CD8+ T cells (N = 19), CD4+ T cells (N = 7), regulatory T cells (Tregs, N = 15), macrophages (N = 13), myeloid-derived suppressor cells (MDSCs, N = 4), and Langerhans cells (LCs, N = 2). Conclusions: Irrespective of tumor location, CD8+ and CD4+ T cells appear to play a key role in the development of HPV−related HNSCC, and their infiltration is likely associated with a significant impact on OS and RFS. To date, the roles and prognostic value of Tregs, macrophages, DCs and MDSCs remain unclear.

Human papilloma virus (HPV) infection as an etiological factor in malignant sinonasal neoplasms and nasopharyngeal carcinomas: A pathologist’s perspective

Human papilloma virus (HPV) infection as an etiological factor in malignant sinonasal neoplasms and nasopharyngeal carcinomas: A pathologist’s perspective - IJPO- Print ISSN No: - 2394-6784 Online ISSN No:- 2394-6792 Article DOI No:- 10.18231/j.ijpo.2019.044, Indian Journal of Pathology and Oncology-Indian J Pathol O

Human papillomavirus in laryngeal and hypopharyngeal lymphoepithelial carcinoma

The involvement of human papillomavirus (HPV) in laryngeal and hypopharyngeal lymphoepithelial carcinoma was investigated in a series of ten cases (seven laryngeal and three hypopharyngeal), retrieved from the files of three tertiary hospitals in the 2000–2017 period, through polymerase chain reaction with SPF10 primers and INNO-LiPA HPV Genotyping Extra II (Innogenetics). Epstein–Barr virus (EBV) was tested in all cases with in situ hybridization INFORM EBER Probe (Ventana Medical Systems). p16 and p53 expression were immunohistochemically analyzed. Calculated annual incidence was 0.013/100,000, and prevalence was 0.2% of laryngeal and hypopharyngeal carcinomas. All cases were EBV negative. HPV was detected in five cases, three of which also overexpressed p16. HPV16 was detected in four cases, and HPV58 in one case. Five cases were HPV negative, only one of these five overexpressed p16. No recurrence was observed in nine cases during follow-up. The 5-year disease-specific-survival rate was 100%. Mean overall survival was 87 months. Lymphoepithelial carcinoma of the larynx and hypopharynx are not related to EBV. Simultaneous HPV+/p16+ is consistent with HPV causation in a fraction of laryngeal and hypopharyngeal lymphoepithelial carcinomas.

HPV and skin carcinogenesis

Epidemiological and biological studies provide several lines of evidence for the involvement of cutaneous beta human papillomaviruses (HPVs), together with ultraviolet (UV) radiation, in the development of cutaneous squamous cell carcinoma. These viruses appear to act with a hit-and-run mechanism, being necessary at an early stage of carcinogenesis and being dispensable for the maintenance of the malignant phenotype. Studies in experimental models show that beta HPVs, mainly via the E6 and E7 oncoproteins, are able to promote proliferation and to circumvent cellular stresses induced by UV radiation. These findings support a model of skin carcinogenesis in which beta HPV-infected keratinocytes remain alive despite the accumulation of UV-induced DNA mutations. In this manner, these cells become highly susceptible to progression towards malignancy. Thus, UV radiation is the main driver of skin cancer development, while beta HPVs act as facilitators of the accumulation of UV-induced DNA mutations.

A systematic review of the HPV-attributable fraction of oropharyngeal squamous cell carcinomas in Germany.

The prevalence of oropharyngeal squamous cell carcinoma (OPSCC) is increasing globally while the prevalence of other head and neck cancers is decreasing. The most likely reasons for this are a decreasing influence of smoking and the growing relevance of infections with the human papilloma virus (HPV) as a risk factor. A rise in the HPV‐attributable fraction (HPV‐AF) of OPSCC has been observed in many countries, yet a comprehensive review of prevalence rates and trends in Germany is lacking. To determine the current HPV‐AF of OPSCC in Germany and to assess whether it has changed during the last decades, we performed a systematic literature review. We screened Medline and EMBASE for studies that reported the tumor HPV status of newly diagnosed OPSCC patients treated at medical centers in Germany by testing for both HPV DNA and p16INK4a overexpression to confirm involvement of HPV in tumorigenesis. Out of 287 screened studies, 14 studies with data from a total of 1819 OPSCC patients treated between 1988 and 2015 were included in the data synthesis. The reported average HPV‐AF varied considerably between the studies, ranging from 11.5% (1988‐2008) to 55.0% (2004‐2009). Two of the included studies did not only provide the HPV‐AF for the entire observed calendar period but also for separate years, allowing to more accurately assess changes over time. These studies reported increases in the HPV‐AF from 21% in 2000 to 53% in 2015 and from 38% in 2004 to 71% in 2013, respectively.

Oncogenic Human Papillomavirus involvement in epithelial ovarian carcinoma among women in Morocco.

Epithelial Ovarian cancer (EOC) although rare is the most lethal gynecological cancer in women worldwide. Despite its high prevalence few studies have been performed to evaluate the prevalence and determinants of HPV infection worldwide. The aim of the present study was to investigate the presence of HPV-DNA in Moroccan patients with EOC using PCR among women in Casablanca, and to examine the prevalence of some HPV genotypes in Moroccan population. We performed a study of HPV detection on Fresh biopsies of 70 epithelial ovarian cancer patients. PCR was realized using the MY09/11 and GP5+/6+ primers. Genotyping of HPV was performed by PCR typespecific for HPV 6, 11, 16, 18, 31, and 33.Data was statistically analyzed using SPSS software. Hence, the mean age was 48.9 years (range,21-76 years). Serous adeno carcinoma (75.71%) and stage III of the disease represent the majority of cases. eight patients were HPV positive (11.42%).Results of HPV genotyping revealed predominance of two genotypes: HPV 16 (87.5%) and HPV 31(12.5).No co-infection identified. Approximately 75% of positive cases had a serous cystadeno carcinoma and more than 62,5% had FIGO advanced stage (III or IV).Our study showed that high-risk HPV infection could play a major role among patients with EOC in Morocco.

Esophageal Squamous Papilloma Associated with Human Papillomavirus

Esophageal squamous papilloma (ESP) is a rare benign tumor of the esophagus. Human papillomavirus is known to infect the genitourinary tract, the anal canal, the respiratory tract, and the skin. It is associated with benign, precancerous and cancerous lesions. Esophageal papillomas, including HPV-induced squamous cell papillomas of the esophagus, are rare, with an incidence ranging from 0.01 to 0.04 percent. We present a case of esophageal HPV induced squamous cell papilloma. A 59-year-old male presented to the clinic with epigastric abdominal pain radiating to the chest, he was treated empirically with Pantoprazole with the resolution of symptoms. The patient underwent Positron Emission Tomography (PET) scan as part of follow-up surveillance for stage IV adenocarcinoma of the lung that was resected two years ago, it showed hypermetabolic focus involving the gastroesophageal junction. Biopsy of the lesion was consistent with the involvement of human papillomavirus with no evidence of dysplasia. This case illustrates the recognizing the role of human papillomavirus in squamous cell papilloma of the esophagus and its association with GERD.

Involvement of Human Papillomaviruses in Cervical Cancer.

Human papillomaviruses (HPV) are the first viruses to have been acknowledged to prompt carcinogenesis, and they are linked with cancers of the uterine cervix, anogenital tumors, and head and neck malignancies. This paper examines the structure and primary genomic attributes of HPV and highlights the clinical participation of the primary HPV serotypes, focusing on the roles that HPV-16 and 18 play in carcinogenesis. The mechanisms that take place in the progression of cervical neoplasia are described. The oncogenic proteins E6 and E7 disrupt control of the cell cycle by their communication with p53 and retinoblastoma protein. Epidemiological factors, diagnostic tools, and management of the disease are examined in this manuscript, as are the vaccines currently marketed to protect against viral infection. We offer insights into ongoing research on the roles that oxidative stress and microRNAs play in cervical carcinogenesis since such studies may lead to novel methods of diagnosis and treatment. Several of these topics are surfacing as being critical for future study. One particular area of importance is the study of the mechanisms involved in the modulation of infection and cancer development at cervical sites. HPV-induced cancers may be vulnerable to immune therapy, offering the chance to treat advanced cervical disease. We propose that oxidative stress, mRNA, and the mechanisms of HPV infection will be critical points for HPV cancer research over the next decade.

Human papillomavirus infection is not involved in esophageal verrucous carcinoma

Verrucous carcinoma of the esophagus (VCE) is a rare variant of squamous cell cancer, with a puzzling clinical, etiological, and molecular profile. The etiological involvement of human papillomavirus (HPV) in the cancer's natural history is controversial. This study considers 9 cases of VCE, focusing on patients' clinical history before surgery, histologic phenotype, immunophenotype (epidermal growth factor receptor [EGFR], E-cadherin, cyclin D1, p16, and p53 expression), HPV infection, and TP53 gene mutational status (exons 5-8). Using 3 different molecular test methods, not one of these cases of VCE featured HPV infection. The only case with synchronous nodal metastasis was characterized by a TP53 missense point mutation in association with high EGFR and low E-cadherin expression levels. In conclusion, HPV infection is probably not involved with VCE, while TP53 gene mutation, EGFR overexpression, and E-cadherin loss might fuel the tumor's proliferation and lend it a metastatic potential.

Human papillomavirus and colorectal cancer.

The involvement of human papillomavirus in carcinogenesis of colorectal cancer is a contentious issue. The presented meta-analysis was performed to systematize the currently available research results on the matter. The analysis was based on the data from 19 studies to assess the association of HPV infection with colorectal cancer. According to the obtained data, researchers determined the statistically significant level of HPV infection in tumor tissue of CRC and the resulting relative risk of developing CRC with HPV infection to be RR (95% CI) = 2.97 (1.42-6.22) with p = 0.0039.

Detection of HPV E7 Transcription at Single-Cell Resolution in Epidermis

Persistent human papillomavirus (HPV) infection is responsible for at least 5% of human malignancies. Most HPV-associated cancers are initiated by the HPV16 genotype, as confirmed by detection of integrated HPV DNA in cells of oral and anogenital epithelial cancers. However, single-cell RNA sequencing may enable prediction of HPV involvement in carcinogenesis at other sites. We conducted single-cell RNA sequencing on keratinocytes from a mouse transgenic for the E7 gene of HPV16 and showed sensitive and specific detection of HPV16-E7 mRNA, predominantly in basal keratinocytes. We showed that increased E7 mRNA copy number per cell was associated with increased expression of E7 induced genes. This technique enhances detection of active viral transcription in solid tissue and may clarify possible linkage of HPV infection to development of squamous cell carcinoma.