Human Papillomavirus Involvement Research Articles

Association of human papillomavirus 16 and 18 with ovarian cancer risk: Insights from a meta‑analysis.

Ovarian cancer (OC) presents a global health challenge, with well-documented genetic aspects. However, to the best of our knowledge, the role of human papillomavirus (HPV) types 16 and 18 in OC remains unclear. The present meta-analysis assessed the prevalence of HPV in OC across 43 studies and included a comparative meta-analysis of 19 case-control studies to determine the association of HPV with OC risk. Subgroup analyses were performed based on geographic regions and histopathological types to explore heterogeneity, and publication bias was evaluated using funnel plots and statistical tests of asymmetry. The pooled prevalence of HPV was found to be 10% (95% CI, 5-18) and 7% (95% CI, 3-15) specifically for HPV 16/18. Case-control studies indicated an odds ratio (OR) of 4.92 (95% CI, 1.96-12.53) for HPV 16/18, with higher pooled prevalence rates of 17% for all HPV genotypes and 13% for HPV 16/18. Notably, Asian countries exhibited the highest HPV prevalence and OR in OC. These findings support the involvement of HPV, particularly HPV 16 and 18, in increasing the risk of OC, emphasizing the need for further research to confirm these associations and explore potential mechanisms.

No genetic causal association between human papillomavirus and lung cancer risk: a bidirectional two-sample Mendelian randomization analysis

IntroductionSeveral observational or retrospective studies have previously been conducted to explore the possible association between lung cancer and human papillomavirus (HPV) infection. However, there may be inconsistencies in the data and conclusions due to differences in study design and HPV testing methods. There are currently no studies that provide conclusive evidence to support the involvement of HPV in the occurrence and development of lung cancer. Therefore, the relationship between HPV and lung cancer remains controversial and uncertain. This study aimed to explore whether HPV infection is causally related to lung cancer risk by systematically performing a two-way Two-Sample Mendelian Randomization (TSMR) analysis.MethodsIn the International Lung Cancer Consortium (ILCCO) genome-wide association study dataset, we included 11,348 lung cancer (LUCA) cases, including 3275 squamous cell carcinoma (LUSC) cases, 3442 adenocarcinoma (LUAD) cases, and 15,861 cases of control. Using genetic variants associated with the HPV E7 protein as instrumental variables, we summarized statistics associated with HPV infection in the MRC IEU OpenGWAS database, which included the HPV-16 E7 protein and the HPV-18 E7 protein. Two-sample Mendelian randomization (MR) results are expressed as odds ratios (OR) and 95% confidence intervals (CI).ResultsBased on a comprehensive analysis of genome-wide association study (GWAS) data from public databases, we mainly used inverse-variance weighted (IVW) to estimate causal relationships, while using MR-Egger, weighted median, simple mode, and weighted mode, and other four methods as supplements. Two-sample MR Analysis revealed no causal relationship between exposure factors (HPV-16 E7 protein and HPV-18 E7 protein) and outcome factors (lung cancer (LUCA) and its subtypes squamous cell carcinoma (LUSC) and adenocarcinoma (LUAD)) in forward MR Analysis using the IVW approach.HPV-16 E7 protein and LUCA and its subtypes LUSC and LUAD by IVW method results: [OR] = 1.002; 95% [CI]: 0.961 − 1.045; p = 0.920; [OR] = 1.023; 95% [CI]: 0.966 − 1.084; p = 0.438; [OR] = 0.994; 95% [CI]: 0.927 − 1.066; p = 0.872); HPV-18 E7 protein and LUCA and its subtypes LUSC and LUAD by IVW method results: [OR] = 0.965; 95% [CI]: 0.914 − 1.019; p = 0.197; [OR] = 0.933; 95% [CI]: 0.834 − 1.043; p = 0.222; [OR] = 1.028; 95% [CI]: 0.945 − 1.118; p = 0.524. It was observed through reverse MR that LUCA and its subtypes LUSC and LUAD were used as exposure factors, and HPV infection (HPV-16 E7 protein and HPV-18 E7 protein) was used as the outcome factors, the results of the IVW method are also invalid.LUCA and HPV-16 E7 protein and HPV-18 E7 protein by IVW method results: [OR] = 1.036; 95% [CI]: 0.761 − 1.411; p = 0.82; [OR] = 1.318; 95% [CI]: 0.949 − 1.830; p = 0.099; LUSC and HPV-16 E7 protein and HPV-18 E7 protein by IVW method results: [OR] = 1.123; 95% [CI]0.847 − 1.489; p = 0.421; [OR] = 0.931; 95% [CI]: 0.660 − 1.313; p = 0.682; LUAD and HPV-16 E7 protein and HPV-18 E7 protein by IVW method results: [OR] = 1.182; 95% [CI] 0.983 − 1.421; p = 0.075; [OR] = 1.017; 95% [CI]: 0.817 − 1.267; p = 0.877.Our results indicate that there is no causal relationship between genetically predicted HPV infection and LUCA and its subtypes LUSC and LUAD. In addition, in the reverse MR analysis, we did not observe a significant causal relationship between LUCA and its subtypes LUSC and LUAD on HPV infection.ConclusionsOur findings do not support a genetic association between HPV infection and lung cancer.

Assessment of Interobserver Agreement Among Gynecologic Pathologists Between Three-Tier Versus Binary Pattern-based Classification Systems for HPV-associated Endocervical Adenocarcinoma.

The three-tier (A vs. B vs. C) pattern-based (Silva) classification system is a strong and fairly reproducible predictor of the risk of lymph node involvement and recurrence of human papillomavirus (HPV)-associated endocervical adenocarcinoma (EA). Recently, a binary pattern-based classification system has been proposed which incorporates the Silva pattern and lymphovascular invasion (LVI) to assign tumors as "low risk" or "high risk" and this may have superior prognostic significance compared with the three-tier system as well as current International Federation of Gynecology and Obstetrics (FIGO) staging of cervix-confined disease. The interobserver reproducibility of this binary system, however, is unknown. Representative slides from 59 HPV-associated EAs (1-3 slides/case) were independently reviewed by 5 gynecologic pathologists who participated in an online training module before the study. In the first review, a pattern was assigned using the three-tier system. On the second review, a "low risk" or "high risk" designation was assigned and the presence or absence of LVI was specifically documented. Interobserver agreement was assessed using Fleiss' kappa. The binary system showed improved interobserver agreement (kappa=0.634) compared with the three-tier system (kappa=0.564), with a higher proportion of cases having agreement between at least 4/5 reviewers (86% vs. 73%). Nineteen and 8 cases showed improved and worse interobserver agreement using the binary system, respectively; the remainder showed no change. 3/5 reviewers showed no intraobserver discrepancy while the remaining 2 did in a small subset of cases (n=2 and 4, respectively). In this study, a binary pattern-based classification system showed improved interobserver agreement compared with the traditional three-tier system.

Molecular mechanisms of human papilloma virus related skin cancers: A review.

The human papillomavirus (HPV) belongs to the Papillomaviridae family of viruses which includes small, double-stranded DNA viral agents. Approximately 90% of HPV infections occur asymptomatically and resolve spontaneously. However, infection with high-risk viral strains can lead to the development of preneoplastic lesions, with an increased propensity to become cancerous. The location of these malignancies includes the oral cavity, cervix, vagina, anus, and vulva, among others. The role of HPV in carcinogenesis has already been demonstrated for the aforementioned neoplasia. However, regarding skin malignancies, the mechanisms that pinpoint the role played by HPV in their initiation and progression still elude our sight. Until now, the only fully understood mechanism of viral cutaneous oncogenesis is that of human herpes virus 8 infection in Kaposi sarcoma. In the case of HPV infection, however, most data focus on the role that beta strains exhibit in the oncogenesis of cutaneous squamous cell carcinoma (cSCC), along with ultraviolet radiation (UVR) and other environmental or genetic factors. However, recent epidemiological investigations have highlighted that HPV could also trigger the onset of other non-melanocytic, for example, basal cell carcinoma (BCC), and/or melanocytic skin cancers, for example, melanoma. Herein, we provide an overview of the role played by HPV in benign and malignant skin lesions with a particular focus on the main epidemiological, pathophysiological, and molecular aspects delineating the involvement of HPV in skin cancers.

Sinonasal Inverted Papilloma: A Case Report from Mali

Inverted papilloma (IP) or also called Schneiderian Papilloma is an unusual and rare type of nasal tumor. Generally benign, but can have osteolytic powers and the possibility of transformation into malignancy during its evolution. Several hypotheses emerge in the literature, however the most frequent remains viral origin with the involvement of human papillomavirus (HPV). This is a case of bilateral inverted papilloma in a 60-year-old male patient at the Reference Health Center of the VI commune of the Bamako-Mali district. The symptoms appeared about 14 months ago, marked by a bilateral anterior rhinorrhea, of gradual appearance, associated with nasal obstruction, epistaxis, headaches and anosmia. Thus the diagnosis was made using physical examination and additional examinations such as the scanner of the facial massif, the anatomopathological examination of the operating room, and the test of the human papillomavirus, which turned out to be positive for HPV16 and HPV18. The management consisted of endonasal surgery, with the complete macroscopic removal of the mass and an average meatotomy accompanied by two years of follow-up after the surgical procedure. Since the PI is an aggressive tumor, its management must require long-term surveillance due to the possibility of recidivism and malignant degeneration finally to act early for these eventualities.

BRCA1 deficiency enhances the aggressiveness of breast cancer cells expressing HPV16 oncoproteins.

The precise etiology of breast cancer is not completely understood, although women with BRCA1 gene mutations have a significantly increased risk of developing the disease. In addition, sporadic breast cancer is frequently associated with decreased BRCA1 gene expression. Growing evidence of Human papillomaviruses (HPVs) infections in breast tumors has raised the possibility of the involvement of HPVs in the pathogenesis of breast cancer. We investigated whether the effects of HPV oncoproteins E6 and E7 were influenced by the expression levels of BRCA1. HPV16E6E7 (prototype or E6D25E/E7N29S Asian variant type) were stably expressed in MDA-MB231 breast cancer cells, wild type for BRCA1, or with BRCA1 knocked down. Expression of HPV16E6E7 oncogenes did not affect BRCA1 levels and the abundance of HPV16E6E7 was not altered by BRCA1 knockdown. BRCA1 levels did not alter HPV16E6E7-dependent degradation of G1-S cell cycle proteins p53 and pRb. However, we found that the expression of G2-M cell cycle protein cyclin B1 enhanced by HPV16E6E7 was impacted by BRCA1 levels. Especially, we found the correlation between BRCA1 and cyclin B1 expression and this was also confirmed in breast cancer samples from a Thai cohort. We further demonstrated that the combination of HPV oncoproteins and low levels of BRCA1 protein appears to enhance proliferation and invasion. Transactivation activities of HPV16E6E7 on genes regulating cell proliferation and invasion (TGF-β and vimentin) were significantly increased in BRCA1-deficient cells. Our results indicate that a deficiency of BRCA1 promotes the transactivation activity of HPV16E6E7 leading to increase of cell proliferation and invasion. HPV infection appears to have the potential to enhance the aggressiveness of breast cancers, especially those deficient in BRCA1.

The community nurse’s role on the promotion of papillomavirus vaccination among young students: A study protocol

ABSTRACT Vaccination is the principal strategy for primary prevention of infection by Human Papilloma Virus (HPV), which causes different pathological conditions, up to cancer, in both males and females. However, to date, knowledge among adolescents and their parents about the HPV vaccine is still low. The aim of this quasi-experimental, multicenter study is to assess the effectiveness of a digital educational intervention, conducted by a multidisciplinary health-care team including a Community Nurse, to increase adolescents’ HPV vaccination uptake, their knowledge, self-efficacy, feelings and involvement in HPV vaccine decision-making, and parents’ vaccination hesitancy. The study will be carried out among a population of students (and their parents), aged between 11 and 13, at secondary schools in Italy. Validated questionnaires will be administered to both students and parents at baseline (T0) and 3 months after a digital educational intervention (T1). The findings may be useful in evaluating and deepening a methodology for designing and implementing educational interventions, embedded in the school setting, that could promote the achievement of outcomes within the broader process of youth’s health promotion.

Are HPV oncogenic viruses involved in salivary glands tumorigenesis?

The association between different viruses and cancer is well acknowledged in human pathology. However, the precise understanding of how oncogenic viruses intervene in the development of cancer of salivary glands (SGs) remains incomplete. Our review aimed to explore the current literature regarding SGs cancer to evaluate the potential involvement of human papillomaviruses (HPVs) in their development. Our work hypothesis suggests that viruses may be involved in these tumors' immunogenicity. The literature analysis showed HPV-positive detection in different head and neck malignancies, added to variable risk factors and a constant increasing incidence rate. HPV tumorigenesis mechanism is complex, involving E6 and E7 HPV oncoproteins. Additionally, the reported findings generally support the relationship between SGs cancer and high oncogenic subtypes 16 and 18. However, the pathogenic contribution of HPV subtypes 11, 33, 45, 52, 56, and 59 is controversial and further research may clarify their potential involvement in the SG tumor's development. This literature review may enhance the understanding of the role of viral contribution as an etiopathogenic co-factor in SG carcinogenesis. Thus, these data may add value to innovative concepts and treatment strategies development, given that virus-induced tumors can be prevented by targeted immunization, added to oncolytic or viral therapy.

Human papillomavirus and prostate cancer: systematic review and meta-analysis

The involvement of human papillomavirus (HPV) in the prostate carcinogenesis is a controversial issue. The presented meta-analysis was carried out to systematize the currently available research results regarding this question. The meta-analysis includes case–control studies from 1991 to 2022, which were collected from publicly available bibliometric databases. The meta-analysis was performed using Meta-Essentials_1.5 software. We used Begg’s and Egger’s methods to assess publication bias. Cochran’s Q test was used to assess heterogeneity and the I2 index was employed for calculating the variation in the pooled estimations. The analysis was based on data from 27 case–control studies, which in total yielded 1607 tumour tissue samples of prostate and 1515 control samples (317 samples of normal tissue, 1198 samples of benign prostatic hyperplasia (BPH)). According to the data obtained, there was high risk of prostate cancer by HPV infection in both cases. HPV was found in prostate cancer in 25.8% of cases, while in normal tissue samples the virus was detected in 9.2% of cases and in 17.4% with BPH as a control. In particular, more studies on the association of HPV and prostate cancer are needed to prove the role of HPV in the development of prostate cancer. In addition to the controversial question of whether HPV infection is associated with prostate cancer risk, it is worth considering whether the samples used as a control have an impact on the results. The impact of HPV in prostate tumour tissue samples on outcome should also be investigated.

Prevalence and genotype distribution of human papillomavirus in cervical adenocarcinoma (usual type and variants): A systematic review and meta-analysis.

Cervical glandular neoplasms represent a heterogeneous group of tumors for which a comprehensive overview of the involvement of high-risk human papillomaviruses (HPV) in pathogenesis is still lacking. We first searched MEDLINE (PubMed), Embase, and Scopus databases (until October 2022), and systematically reviewed available literature. We then quantitatively estimated both pooled and genotype-specific prevalence of HPV DNA as well as the influence of various factors (e.g., geographical region, histological subtype, tissue/sample type) on computed effect size by means of random effects meta-analysis. In total, 379 studies comprising 17 129 cases of cervical adenocarcinoma were identified. The pooled HPV prevalence was 78.4% (95% confidence interval [95% CI]: 76.2-80.3) with a significant between-study heterogeneity (I2 = 79.4%, Q test p < 0.0001). Subgroup analyses indicated that the effect size differed substantially by geographical region (from 72.5% [95% CI: 68.7-76.1] in Asia to 86.8% [95% CI: 82.2-90.3] in Oceania) (p < 0.0001) and histological subtype of cancer (from 9.8% [95% CI: 5.5-17] in gastric-type to 85% [95% CI: 79.6-89.2] in usual-type cervical adenocarcinoma) (p < 0.0001). HPV16 and HPV18 were by far the most frequently detected viral strains with specific prevalence of 49.8% (95% CI: 46.9-52.6) and 45.3% (95% CI: 42.8-47.8), respectively. When stratified by continent or histologic variant, these genotype-specific results varied in a relatively limited manner. Altogether, these findings support that all histological subtypes of cervical adenocarcinoma are etiologically linked to high-risk HPV but to varying degrees. Therefore, a dual-criteria classification taking into account accurately both morphological and virological aspects could be an interesting evolution of the current binary World Health Organization classification, better reflecting the pathogenic diversity of the disease.

HPV and Other Risk Factors Involved in Pharyngeal Neoplasm-Clinical and Morphopathological Correlations in the Southwestern Region of Romania.

Oropharyngeal squamous cell carcinoma (OPSCC) development is strongly associated with risk factors like smoking, chronic alcohol consumption, and the living environment, but also chronic human papilloma virus (HPV) infection, which can trigger cascade cellular changes leading to a neoplastic transformation. The prevalence of these factors differs among different world regions, and the prevention, diagnosis, and prognosis of OPSCC are highly dependent on them. We performed a retrospective study on 406 patients diagnosed with OPSCC in our region that were classified according to the tumor type, localization and diagnosis stage, demographic characteristics, risk factors, and histological and immunohistochemical features. We found that most of the patients were men from urban areas with a smoking habit, while most of the women in our study were diagnosed with tonsillar OPSCC and had a history of chronic alcoholism. During the immunohistochemical study, we analyzed the tumor immunoreactivity against anti-p16 and anti-HPV antibodies as markers of HPV involvement in tumor progression, as well as the correlation with the percentage of intratumoral nuclei immunomarked with the anti-Ki 67 antibody in serial samples. We observed that the percentage of Ki67-positive nuclei increased proportionally with the presence of intratumoral HPV; thus, active HPV infection leads to an increase in the rate of tumor progression. Our results support the implementation of strategies for OPSCC prevention and early diagnosis and can be a starting point for future studies aiming at adapting surgical and oncological treatment according to the HPV stage for better therapeutic results.

HPV16 E6 and E7 are involved in inhibition of autophagy and maintenance of cancer stem cell properties in HPV16‐positive oral squamous cell carcinoma cells

AbstractAimThe involvement of human papillomavirus (HPV) E6/E7 in autophagy has not been fully elucidated in oral squamous cell carcinoma (OSCC) cells. The objective of this study was to clarify the association between HPV E6/E7 and autophagy and cancer stem cell properties such as self‐renewal ability and chemotherapy resistance in HPV16‐positive OSCC cells.MethodsUM‐SCC‐104 HPV16‐positive OSCC cells were cultured on laminin 332‐coated silicone gel. The impact of HPV16 E6 or E7 siRNA transfection on cell proliferation, spheroid formation, 5‐fluorouracil (5‐FU)‐induced cell death, and autophagy was investigated. After treatment with rapamycin, DAPGreen was used to detect autophagosome formation.ResultsHPV16 E6 or E7 siRNA transfection resulted in knockdown of both E6 and E7 in UM‐SCC‐104 cells. HPV16 E6/E7 knockdown inhibited cell proliferation, mRNA expression of stem cell markers (i.e., CD44, ALDH1, BMI1, OCT4, and NANOG), and spheroid formation. Furthermore, HPV16 E6/E7 knockdown enhanced 5‐FU‐induced cell death. Additionally, mRNA expression of autophagy‐related genes such as ATG5 and BECN1 was significantly increased after HPV16 E6/E7 knockdown. Furthermore, HPV16 E6/E7 knockdown augmented rapamycin‐induced autophagy. Next, we found that miR‐30a‐5p is indicated to interact with the 3′‐untranslated region of ATG5 and BECN1 using TargetScan. However, significant induction of autophagy was not found after miR‐30a‐5p inhibitor transfection. Importantly, 5‐FU‐induced cell death was significantly attenuated by chloroquine autophagy inhibitor in HPV16 E6/E7 knockdown cells.ConclusionHPV16 E6/E7 is involved in autophagy regulation as well as in the maintenance of cancer stem cell features in OSCC cells.

LncRNA SELL/L-selectin promotes HPV-positive HNSCC progression and drives fucoidan-mediated therapeutic strategies

Positive human papillomavirus (HPV+) head and neck squamous cell carcinoma (HNSCC) presents a higher risk of lymph node metastasis and poor prognosis. Here, advanced microarray analysis of clinically collected HNSCC tissues revealed significant upregulation of the lncRNA SELL in HPV+ HNSCC, and its overexpression was obviously associated with lymph node metastasis. The lncRNA SELL could function as a promigratory and proinvasive mediator as well as an inducer of M1-like tumour-associated macrophages (TAM) by increasing the level of L-selectin. Furthermore, fucoidan, as an L-selectin inhibitor, obviously weakened the formation of tongue lesions induced by 4-Nitroquinoline N-oxide (4-NQO) in HPV16 E6/E7 transgenic mice. This result drove us to synchronously develop a nanodelivery platform to verify fucoidan-mediated anti-growth and anti-metastasis effects. This work highlighted the important influence of the lncRNA SELL/L-selectin on promoting HPV+ HNSCC progression and proposed a potential fucoidan-mediated therapeutic strategy. Statement of significanceHead and neck squamous cell carcinoma (HNSCC) patients with human papillomavirus (HPV) involvement present a greater risk of lymph node metastasis than HPV negative HNSCC patients. However, treatment protocols, including surgery and platinum-based chemo- and radiotherapy, have not improved the 5-year overall survival due to the high tendency of lymphatic metastasis. Here, microarray of clinical HNSCC samples confirms the oncogenic significance of lncRNA SELL, which acts as an M1-like TAM inducer and promotes tumorigenesis by upregulating L-selectin. Fucoidan, as an L-selectin inhibitor, suppresses tongue lesions in transgenic mice, and a fucoidan-mediated nanodelivery platform inhibits HPV+ HNSCC growth. The present study highlights lncRNA SELL/L-selectin on promoting HPV+ HNSCC progression and proposes a potential fucoidan-mediated therapeutic.

Human papilloma virus presence and its physical status in primary pterygium

Pterygium is one of the most frequent pathologies in ophthalmology, and is a benign, overgrowth of fibrovascular tissue, often with a wing-like appearance, from the conjunctiva over the cornea. It is composed of an epithelium and highly vascular, sub-epithelial, loose connective tissue. There is much debate surround the pathogenesis of pterygium and a number of theories have been put forward including genetic instability, cellular proliferation, inflammatory influence, and degeneration of connective tissue, angiogenesis, aberrant apoptosis and viral infection. At present, the involvement of human papillomavirus (HPV) in the genesis of pterygium is controversial, as have reported that HPV is present in 58% of cases, while others have failed to detect HPV in pterygium. In this study, we evaluated the presence and viral genotype of HPV DNA in pterygia and healthy conjunctiva sample, and virus integration into the cellular genome.Forty primary pterygia samples and 12 healthy conjunctiva samples were analyzed to HPV DNA presence by polymerase chain reaction, using MY09/MY11 primers of HPV-L1 gene. Viral genotype was identified by DNA sequence analysis of this amplicon. HPV integration into the cellular genome was analyzed by western blot detecting HPV-L1 capsid protein.Presence of HPV was observed in 19 of the 40 pterygia samples. In contrast, healthy conjunctiva samples were negative. To determine virus type, sequence analyses were performed. Interestingly, 11 out of the 19-pterygium samples were identified as HPV-11 type, meanwhile, the remaining 8 pterygium samples were identified as HPV-18. HPV-L1 capsid protein were found only in 3 out of the 10 samples studied.In conclusion, our study identified the presence of HPV DNA exclusively in pterygium samples and described HPV-11 and -18 genotypes. Our results suggest that HPV may be involved in the pathogenesis of pterygium. On the other hand, the expression of the L1-HPV protein suggests viral integration into the cellular genome.

Expression of Human Papillomavirus and the p16 Gene in Oral Potentially Malignant Disorders (OPMD): a Comparative Study With Oral Squamous Cell Carcinoma.

The incidence of oral squamous cell carcinoma (OSCC) of the tongue is increasing in the younger population without traditional risk habits that lead researchers to find other related factors such as diet and viruses, especially human papillomavirus (HPV). It is noteworthy that many OSCCs develop from oral potentially malignant disorders (OPMDs). Correct diagnosis and timely management of OPMDs may help to prevent malignant transformation, and therefore it is worth seeing the involvement of HPV in OPMDs and oral cancers, as the preventive and curative measures in HPV-induced cancer types are different from the conventional types of OPMDs and OSCCs. Therefore, the main objective of this study was to identify a relationship between HPV and p16 in OPMDs and compare it with OSCC. This study was conducted on 83 cases of known OSCCs and OPMDs (oral submucous fibrosis, leukoplakia, and oral lichen planus). Assays, such as polymerized chain reaction (PCR) and reverse transcription-PCR, were carried out for HPV and p16. The results were compared with clinical information and with the literature. The results were analyzed using SPSS 16.0 for windows. P16 expression was mostly seen in males than in female patients. Out of 21 cases of keratosis with dysplasia, 19% expressed p16. Of 26 oral lichen planus patients, 29% showed the p16 gene with immunohistochemistry. Interestingly, a high percentage of OSF cases expressed p16 (48.27%). Minimal expression was observed in OSCC (6.25%). HPV DNA was detected in 2.4% of the total sample. Both p16 and HPV were detected in a single case of OSCC. OPMDs expressed a significant amount of the p16 gene by immunohistochemistry and reverse transcription-PCR technique when compared with malignant lesions, suggesting a possible inactivation of the p16 gene. HPV and p16 are mostly negative in our OSCC sample, exhibiting low prevalence. OPMDs expressed a significant amount of the p16 gene when compared with malignant lesions, suggesting a possible inactivation of the p16 gene. Although OSF expressed p16, HPV was not detected, suggesting that over-expression could be independent of HPV. OSCC shows low HPV prevalence.

Detection of Human Papilloma Virus (HPV) Infection in Colorectal Cancer and Viral Genome Integration Status

Background: Colorectal cancer (CRC) is the third common cause of malignancy in Iran, and its incidence rate has been raised due to an increase in individual and environmental risk factors. Objectives: The present study aimed to define the role of human papillomavirus (HPV) infection in CRC, then by drawing a phylogenetic tree, we aimed to analysis the sequences of isolated HPVs, and finally determine the viral genome physical status for HPV-16. Methods: A nested-PCR (nPCR), direct sequencing, and INNO-LiPA HPV genotyping assay were carried out for HPV detection, and a quantitative real-time PCR assay (qRT-PCR) was conducted for the physical status of the viral genome. Results: Among 157 subsets, there were 66 cases and 91 controls. Moreover, 5.7% (9/157) were HPV positive by nPCR, among whom 9.1% (6/66) were cases and 3.3% (3/91) were control groups (P = 0.750). The qRT-PCR analysis showed three forms of integrated, episomal, and mixed forms in our three HPV-16 strains. A higher rate of HPV infection was detected in the CRC cases; however, it was not statistically significant. Conclusions: Although there were limited positive results, higher ages (&gt; 65) were related to HPV involvement and CRC outcome. Furthermore, 9.1% of the CRC cases were infected with HPVs. The HPV-16 genome integration is observed in high-grade cancer cases with severe malignancy in CRC patients.

The Dysregulation of MicroRNAs in the Development of Cervical Pre-Cancer-An Update.

Globally in 2020, an estimated ~600,000 women were diagnosed with and 340,000 women died from cervical cancer. Compared to 2012, the number of cases increased by 7.5% and the number of deaths increased by 17%. MiRNAs are involved in multiple processes in the pathogenesis of cervical cancer. Dysregulation of miRNAs in the pre-stage of cervical cancer is the focus of this review. Here we summarize the dysregulated miRNAs in clinical samples from cervical pre-cancer patients and relate them to the early transformation process owing to human papillomavirus (HPV) infection in the cervical cells. When HPV infects the normal cervical cells, the DNA damage response is initiated with the involvement of HPV’s E1 and E2 proteins. Later, cell proliferation and cell death are affected by the E6 and E7 proteins. We find that the expressions of miRNAs in cervical pre-cancerous tissue revealed by different studies seldom agreed with each other. The discrepancy in sample types, samples’ HPV status, expression measurement, and methods for analysis contributed to the non-aligned results across studies. However, several miRNAs (miR-34a, miR-9, miR-21, miR-145, and miR-375) were found to be dysregulated across multiple studies. In addition, there are hints that the DNA damage response and cell growth response induced by HPV during the early transformation of the cervical cells are related to these miRNAs. Currently, no review articles analyse the relationship between the dysregulated miRNAs in cervical pre-cancerous tissue and their possible roles in the early processes involving HPV’s protein encoded by the early genes and DNA damage response during normal cell transformation. Our review provides insight on spotting miRNAs involved in the early pathogenic processes and pointing out their potential as biomarker targets of cervical pre-cancer.

The Involvement of Human Papilloma Virus in Gastrointestinal Cancers.

Simple SummaryMounting evidence suggests a relationship between Human Papilloma Virus (HPV) infection and the occurrence of neoplastic transformations within oral, pharyngeal, and anal cancers. Other segments of the intestinal tract can also be involved. Knowledge about the association between HPV infection and gastrointestinal carcinogenesis is crucial for both cancer prevention and patient care. Unfortunately, definite conclusions cannot be drawn yet, due to the high number of contradictions in the published papers.Human Papilloma Virus (HPV) is one of the most common sexually transmitted infections worldwide. HPV infection has a strong relationship with the onset of cervix uteri, vagina, penis, anus, and oropharynx, but also tonsils and tongue cancers. Some epidemiological data indicate that except for gynecologic cancers, HPV infection can be one of the risk factors associated with a greater risk of induction and progression of gastrointestinal cancers. Data, however, remain contradictory and definite conclusions cannot be drawn, so far. The following review aims to organize recent evidence and summarize the current state of knowledge regarding the association between HPV infection and gastrointestinal tumors primarily focusing on esophageal, liver, gastric, colorectal, and anal cancers.

Detection of Human PapillomaVirus and its Association with Potentially Malignant Disorders and Oral Squamous Cell Carcinoma: A Retrospective Study.

Aim:This study was carried out with the objective of recognizing the involvement of human papillomavirus (HPV) in conditions of oral squamous cell carcinoma (OSCC) and oral potentially malignant conditions and lesions.Materials and Methods:OSCC samples from thirty patients were collected and thirty paraffin-embedded, oral premalignant specimens were collected. It was decided to use as a negative control samples gingiva from healthy individuals who had no prior history of oral proliferative leukoplakia or OSCC. The samples were then processed using a paraffin-embedded tissue block method. Deoxyribonucleic acid will be extracted from the paraffin-embedded tumor sample of sixty case subjects and tested for the presence of HPV DNA using polymerase chain reaction.Results:In study Group 1, 24 samples were taken from males and 6 from females. In study Group 2, 26 cases were males and 4 were females. In Group 1, 16 cases of moderately differentiated and 14 cases of well differentiated each were present. No case of poorly differentiated were found. There was statistically no significant difference present between male and female when Group 1 and Group 2 was considered. In study Group 1, 0 samples had positive HPV DNA detection, whereas 30 samples had negative HPV DNA detection. In study Group 2, 0 samples had positive HPV DNA detection, whereas 30 samples had negative HPV expression.Conclusion:According to our findings, certain incidences of OSCC may be linked to HPV, however, this was not the case for all of the cancers.

Lymphoepithelial carcinoma of the parotid gland: a unique example showing p16 immunoreactivity.

Lymphoepithelial carcinoma (LEC) shows characteristic histology of nesting growth of tumor cells with unclear differentiation against the lymphoid stroma background. Although rare in salivary glands, it has previously been recognized as a type of undifferentiated carcinoma but is currently clearly defined as an independent disease separate from undifferentiated carcinoma. We report a case of LEC that developed in the parotid gland and was immunohistochemically positive for p16, which suggested the causative involvement of human papillomavirus (HPV). The patient was a 38-year-old Japanese male aware of mass formation in the left parotid area for 8years. Parotidectomy was performed and there have been no signs of recurrence or metastasis for 18month post-operation. The tumor was histologically typical except for Epstein-Barr virus (EBV)-encoded small RNA (EBER)-negative in situ hybridization (ISH), but p16-positivity by immunohistochemistry, and also frequent contact with extended and expanded pre-existing ductal structures. Although usually strongly associated with EBV infection, the tumor could be regarded to have eventually reached completion as a LEC lesion associated with HPV infection possibly through the pathway shared with squamous cell carcinoma. EBER-ISH remains the most promising index for confirming diagnosis of LEC, but EBV-negative result alone should not prevent diagnosis of LEC.