Role of human papillomavirus in the pathogenesis of oral squamous cell carcinoma

Oral cancer is one of the most common cancers and it constitutes a major health problem particularly in developing countries. Oral squamous cell carcinoma(OSCC) represents the most frequent of all oral neoplasms. Several risk factors have been well characterized to be associated with OSCC with substantial evidences. While tobacco and alcohol are the primary risk factors for OSCC development, many epidemiological studies report a strong association with human papillomavirus(HPV) in a subset of OSCC. This article presents our current knowledge on the relationship between HPV and development of OSCC. HPVs are DNA viruses that specifically target the basal cells of the epithelial mucosa. Most experimental data are consistent with the hypothesis that HPV plays a causal role in oral carcinogenesis. Genotypes, such as HPV1 infect epidermal cells, whereas HPV6, 11, 16 and 18 infect epithelial cells of the oral cavity and other mucosal surfaces. Several studies have shown that there is an increased risk of head and neck cancer in the two major HPV 16 oncogenes E6 and E7-positive patients. The presence of antibodies to HPV E6 and E7 proteins was found to be more associated with tumors of the oro-pharynx than of the oral cavity. However, HPV alone appears to be insufficient as the cause of OSCC but requires other co-factors. Although a viral association within a subset of OSCC has been shown, the molecular and histopathological characteristics of these tumors have yet to be clearly defined.

Role of human papillomavirus in oropharyngeal squamous cell carcinoma: A review

Human papillomavirus(HPV) has been implicated in the pathogenesis of a subset of oropharyngeal squamous cell carcinoma. As a result, traditional paradigms in relation to the management of head and neck squamous cell carcinoma have been changing. Research into HPVrelated oropharyngeal squamous cell carcinoma is rapidly expanding, however many molecular pathological and clinical aspects of the role of HPV remain uncertain and are the subject of ongoing investigation. A detailed search of the literature pertaining to HPV-related oropharyngeal squamous cell carcinoma was performed and information on the topic was gathered. In this article, we present an extensive review of the current literature on the role of HPV in oropharyngeal squamous cell carcinoma, particularly in relation to epidemiology, risk factors, carcinogenesis, biomarkers and clinicalimplications. HPV has been established as a causative agent in oropharyngeal squamous cell carcinoma and biologically active HPV can act as a prognosticator with better overall survival than HPV-negative tumours. A distinct group of younger patients with limited tobacco and alcohol exposure have emerged as characteristic of this HPV-related subset of squamous cell carcinoma of the head and neck. However, the exact molecular mechanisms of carcinogenesis are not completely understood and further studies are needed to assist development of optimal prevention and treatment modalities.

Human Papillomavirus as an Independent Predictor in Oral Squamous Cell Cancer

Aim There is an increasing evidence for the role of high risk human papillomavirus （HPV） in the pathogenesis of oral squamous cell carcinoma （OSCC）. The purpose of this study is to evaluate the relevance of HPV infection to the survival and prognosis of OSCC. Methodology Fifty-two patients with OSCC were followed from 4 to 88 months with a median of 50.7 months. HPV DNA was identified in formalin-fixed, paraffin-embedded tumor specimens by nested PCR with MY09/MY11 and GP5^＋/GP6^＋ primer pairs and the HPV genotype was determined by direct DNA sequencing. Association between the HPV status and risk factors for cancer as well as tumor-host characteristics were analyzed.Survival curves were calculated by the Kaplan-Meier method and analyzed using the log-rank test. Results HPV was found in 40.4% of the tumors with HPV16 accounting for 63.5%, HPV18 for 30.8%, HPV6 for 3.9% and HPVll for 1.8%. No infection with more than one HPV genotype was detected. HPV infection was significantly associated with poor histological grade, TNM stage Ⅰ -Ⅱ, alcohol usage and no smoking status. Multivariate analysis showed that HPV had an independent prognostic effect on the overall survival after adjusting other confounding factors such as histological grade, TNM stage and tobacco usage. The presence of HPV was significantly correlated with a better survival in patients with OSCC. Conclusion HPV infection can act as an independent predictor for the survival and prognosis of OSCC.

Multimodality functional imaging using DW-MRI and 18F-FDG-PET/CT during radiation therapy for human papillomavirus negative head and neck squamous cell carcinoma: Meixoeiro Hospital of Vigo Experience

AIMTo noninvasively investigate tumor cellularity measured using diffusion-weighted magnetic resonance imaging (DW-MRI) and glucose metabolism measured by 18F-labeled fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG-PET/CT) during radiation therapy (RT) for human papillomavirus negative (HPV-) head and neck squamous cell carcinoma (HNSCC).METHODSIn this prospective study, 6 HPV- HNSCC patients underwent a total of 34 multimodality imaging examinations DW-MRI at 1.5 T Philips MRI scanner [(n = 24) pre-, during- (2-3 wk), and post-treatment (Tx), and 18F-FDG PET/CT pre- and post-Tx (n = 10)]. All patients received RT. Monoexponential modeling of the DW-MRI data yielded the imaging metric apparent diffusion coefficient (ADC) and the mean of standardized uptake value (SUV) was measured from 18F-FDG PET uptake. All patients had a clinical follow-up as the standard of care and survival status was documented at 1 year.RESULTSThere was a strong negative correlation between the mean of pretreatment ADC (ρ = -0.67, P = 0.01) and the pretreatment 18F-FDG PET SUV. The percentage (%) change in delta (∆) ADC for primary tumors and neck nodal metastases between pre- and Wk2-3 Tx were as follows: 75.4% and 61.6%, respectively, for the patient with no evidence of disease, 27.5% and 32.7%, respectively, for those patients who were alive with disease, and 26.9% and 7.31%, respectively, for those who were dead with disease.CONCLUSIONThese results are preliminary in nature and are indicative, and not definitive, trends rendered by the imaging metrics due to the small sample size of HPV- HNSCC patients in a Meixoeiro Hospital of Vigo Experience.

The Relationship between Human Papillomavirus and Oesophageal Squamous Cell Carcinoma in China—A Review of the Evidence

Background: China has one of the highest incidence rates of oesophageal cancer in the world. The role of human papillomavirus (HPV) has been extensively researched in oesophageal squamous cell carcinoma (OSCC) with indeterminate results. The majority of these studies have been conducted in the Chinese population. Evidence for a definitive HPV-OSCC association could potentially support prophylactic vaccination in target populations, highlighting the need for ongoing investigation. The aim of this review is to summarise the findings of HPV DNA in OSCC tissue in Chinese subjects, with a view to informing further research in this area. Methods: A systematic literature search of the Chinese National Knowledge Infrastructure (CNKI) database, Medline, Embase and PubMed was conducted for all studies in English and Chinese language, examining OSCC tissue for HPV DNA in China. Reference lists of retrieved articles were reviewed and hand searches of relevant, key journals were conducted, to source articles which were not electronically indexed. Sixty-four studies met our selection criteria. Data from case-control and cross-sectional studies were analysed separately for any HPV-OSCC association, using the Epi InfoTM 3.5.3 software program. Results: From all studies conducted in the Chinese population, 2166/5953 (36%) of all OSCC tissue and 478/1684 (28%) of healthy control tissue, tested positive for HPV. We found that 11/16 case-control and cross-sectional studies had a statistically significant crude odds ratio, which supported a potential HPV-OSCC association. The largest study, carried out in the high incidence County of Anyang in Henan Province, reported 207/265 (78%) OSCC tissues testing positive for HPV DNA against 203/357 (57%) controls and had an unadjusted odds ratio of 2.71 (p-value Conclusion: A rigorous meta-analysis would improve interpretation of the data and a well-designed large-scale case-control study is warranted. If a link is found between HPV and OSCC, prophylactic HPV vaccines could be of significant benefit in China.

Effect of Collagen Type I or Human Fibronectin on Imatinib Cytotoxicity in Oral Squamous Cell Carcinoma

Extracellular matrix (ECM) components are critical for all aspects of cell proliferation, adhesion, and morphological alteration. Recent progress has yielded multiple molecular drugs that specifically target gene products which are expressed at high levels in tumor cells. We investigated whether the sensitivity of tumor cells to molecular target drugs could be altered when cells were cultured on surfaces with various coating conditions such as lysine, laminin, Matrigel, collagen type I, and human fibronectin (HFN). This study evaluates the IC50 values of imatinib in oral squamous cell carcinoma (OSCC) cell lines when cells are cultured on plates coated with ECM components such as collagen type I and HFN. Four OSCC cell lines—SQUU-A, SQUU-B, SAS, and NA— are used. Cell proliferation was assessed using WST-8 reagent. Collagen type I and HFN significantly enhanced OSCC cell proliferation compared with control. Imatinib cytotoxicity was demonstrated following culture of OSCCs in culture plates coated with collagen type I or HFN. However, there were no significant changes in imatinib IC50 values between collagen type I and HFN. These results indicate that some molecular target drugs exhibit cancer cell cytotoxicity without being influenced by cell environment factors such as the ECM. These results may aid in the search for molecular target drugs to apply in the clinical chemotherapy of OSCC.

The Effect of MMP-9 Inhibitors on the Biological Behavior of Human Oral Squamous Cell Carcinoma SCC15 Cell Line Through PI3K/Akt Signaling Pathway

Objective:To investigate the effect of MMP-9 inhibitor(Mki67)on the biology of human oral squamous cell carcinoma SCC15 cell line and to explore its mechanism of action through PI3K/Akt signaling pathway.Methods:SCC15 cells were extracted,and the supernatant was discarded.The cells were then rinsed twice with PBS,and 0,2.5,5,and 10μL of Mki67(50 mg/mL)were added to the culture respectively.The inhibition rate of cell proliferation was detected by 3-(4,5-dimethylthiazolyl-2)-2,5-diphenyltetrazolium bromide(MTT)method,and the cell migration was measured by Transwell chamber test.The cell apoptosis rate was detected by cytometry,and the p-Akt protein content in the cells of each group was determined by a double-antibody sandwich enzyme-linked immunosorbent assay(ELISA)kit.Results:The cell proliferation rates of the 2.5μL,5μL,and 10μL dose groups were all lower than the 0μL group(P<0.05)before treatment,and the cell proliferation rates in the 2.5μL,5μL,and 10μL dose groups decreased overtime(P<0.05).After 24 h,with the increase of Mki67 concentration,the number of migration and invasion gradually decreased(P<0.05),and the number of apoptosis gradually increased(P<0.05);besides,the relative expression of MMP-9,PI3K,and Akt mRNA decreased gradually(P<0.05),and the expression level of Akt mRNA was not statistically significant(P>0.05).Conclusion:MMP-9 inhibitor(Mki67)can inhibit the proliferation and migration of SCC15 cell line and induce apoptosis,and its mechanism of action may be related to the inhibition of PI3K/Akt signaling pathway.

Evidence of human papilloma virus infection and its epidemiology in esophageal squamous cell carcinoma

AIM： To look for the evidence of human papilloma virus （HPV） infection in esophageal squamous cell carcinomas （ESCC） and to investigate the potential role and epidemiology of HPV infection in the pathogenesis of esophageal carcinomas in Henan emigrants. METHODS： Papilloma virus （PV） and HPV were determined by UltrasensiveTM S-P immunohistochemistry （IHC） and in situ hybridization （ISH） in esophageal carcinoma tissues （82 cases） and the normal mucosa （40 cases）. RESULTS： IHC revealed that the positive rate of PV was 75.0%, 68.18% and 72.5% respectively while the HPV （16/18-E6） positive rate was 45.0%, 36.36%, 37.5%, respectively in esophageal carcinoma tissue specimens from Henan emigrants,the local citizens and patients in Hubei Cancer Hospital. The PV and HPV （16/18-E6） were negative in all normal esophageal mucosa specimens. No correlation was found between HPV in esophageal squamous cell carcinoma tissues and in grade 1-3 esophageal squamous cell carcinoma cells. In situ hybridization showed that the HPV （16/18） DNA positive rate was 30.0%, 31.8%, 25.0%, respectively in the 3 groups of samples. No positive hybridization signal was found in 40 normal esophageal mucosa specimens. The positive rate of HPV （16/18） DNA in the esophageal carcinoma specimens was significantly higher than that in normal mucosa specimens （P〈0.05）. The positive rate was not different among the 3 groups of esophageal carcinoma tissue specimens （P〉0.05）.CONCLUSION： HPV infection is high in esophageal carcinoma of Henan emigrants, local residents and patients in Hubei Cancer Hospital. HPV is closely related with esophageal squarnous cell carcinoma. HPV infection may play an important role in esophageal squarnous cell carcinoma.

The role of Langerhans cells in oral squamous cell carcinoma

During the initiation, promotion, and progression of multi-step carcinogenesis, changes in specific host immuno- logical factors have been observed. Although immunology of oral cancer has long been focused on antigens and lymphocytes, the fact remains that the antigen presenting cells, like the Langerhans cells （LCs） of the epithelium are initiators and modulators of the immune response. LCs as sentinels of immune response, have been investigated in several orai mucosal diseases, including cancer. Inadequate presentation of tumor antigens by host dendritic cells is one potential mechanism that allows tumor progression, tn this review, the role of LCs in OSCC is discussed. Elucidation of the role of APCs, in particular LCs, may help to better understand the mechanisms underlying anti-tumour immune responses and, improve the effectiveness of anti-cancer immunity in tumour-bearing hosts. This section focuses on the roles LCs in the immunity of cancer and how cancer bypasses the dendritic cell-mediated immune responses, are discussed. Subsequently, the effects of tumor microenviornment on LC＇s and their therapeutic implications are elaborated.

Nomograms based on HPV load for predicting survival in cervical squamous cell carcinoma: An observational study with a longterm follow-up

Objective: To investigate the prognostic value of pretreatment human papillomavirus(HPV) viral load for cervical cancer, and to develop nomograms based on HPV load and other clinicopathological factors for long-term survival.Methods: We conducted a prospective study on cervical squamous cell carcinoma(SCC) patients diagnosed between January 2003 and December 2008. Cervical samples were tested for HPV viral load by the Hybrid Capture II(HCII) assay before treatment and 6 months after treatment. Clinical characteristics and follow-up information were also collected. A multivariable Cox proportional hazards model was used to adjust covariates in both the radical hysterectomy(RH) treatment group and concurrent chemoradiotherapy(CCRT) treatment group to identify relevant covariates, and then nomograms were constructed and used for internal validation.Results: A total of 520 SCC patients enrolled in this study with a median follow-up of 127 months, 360 patients received RH, whereas 160 patients received CCRT. The median HPV viral load in RH and CCRT groups was356.10 and 294.29, respectively. Tumor size was positively correlated with high pretreatment HPV load in both groups. In CCRT group, the advanced International Federation of Gynecology and Obstetrics(FIGO) stage and enlarged retroperitoneal lymph node status determined by computed tomography(LNSCT) were correlated with low HPV load group. Initial HPV viral load, FIGO stage and lymph node metastasis were prognostic factors for RH group, whereas HPV viral load, squamous cell carcinoma antigen(SCC-Ag) level and LNSCT were identified as prognostic factors for CCRT group. Nomograms incorporating these predictors for 10-year progression-free survival(PFS) were constructed [concordance index(C-index): 0.756, 0.749].Conclusions: A low pretreatment HPV viral load is an independent prognostic factor for poor prognosis of cervical SCC and is related to other clinicopathological factors. The survival nomogram based on HPV viral load could predict the long-term prognosis.

No evidence of HPV DNA in esophageal squamous cell carcinoma in a population of Southern Brazil

AIM:To investigate the association between human papillomavirus(HPV)and esophageal squamous cell carcinoma(ESCC)in southern Brazil.METHODS:We studied 189 esophageal samples from125 patients from three different groups:(1)102 biopsies from 51 patients with ESCC,with one sample from the tumor and another from normal esophageal mucosa distant from the tumor;(2)50 esophageal biopsies from 37 patients with a previous diagnosis of head and neck squamous cell carcinoma(HNSCC);and(3)37 biopsies from esophageal mucosa with normal appearance from 37 dyspeptic patients,not exposed to smoking or alcohol consumption.Nested-polymerase chain reaction(PCR)with the MY09/11 and GP5/6 L1primers was used to detect HPV L1 in samples fixed in formalin and stored in paraffin blocks.All PCR reactions were performed with a positive control(cervicovaginal samples),with a negative control(Human Genomic DNA)and with a blank reaction containing all reagents except DNA.We took extreme care to prevent DNA contamination in sample collection,processing,and testing.RESULTS:The histological biopsies confirmed the diagnosis of ESCC in 52 samples(51 from ESCC group and 1 from the HNSCC group)and classified as well differentiated(12/52,23.1%),moderately differentiated(27/52,51.9%)or poorly differentiated(7/52,13.5%).One hundred twenty-eight esophageal biopsies were considered normal(51 from the ESCC group,42 from the HNSCC group and 35 from dyspeptic patients).Nine had esophagitis(7 from the HNSCC and 2 from dyspeptic patients).Of a total of 189 samples,only 6 samples had insufficient material for PCR analysis:1 from mucosa distant from the tumor in a patient with ESCC,3from patients with HNSCC and 2 from patients without cancer.In 183 samples(96.8%)GAPDH,G3PDH and/orβ-globin were amplified,thus indicating the adequacy of the DNA in those samples.HPV DNA was negative in all the 183 samples tested:52 with ESCC,9 with esophagitis and 122 with normal esophageal mucosa.CONCLUSION:There was no evidence of HPV infection in different ESCC from southern Brazil.

Relationship between FHIT Expression and HPV Status in Vulvar Squamous Cell Carcinomas

OBJECTIVE To investigate the relationship between fragilehistidine triad (FHIT) depletion and human papillomavirus (HPV)status in the vulvar squamous cell carcinomas (VSCC).METHODS Immunohistochemical method was used to detectthe expression of FHIT protein in 42 cases of VSCC and 10 casesof normal vulvar tissues. PCR was used to detect HPV infectionstatus. We analyzed the relationship of the expression of FHITprotein between the 2 groups: HPV positive and HPV negative, aswell as the clinically pathological characteristics.RESULTS The expression of FHIT was positive in all normal vul-var tissues, and 71.4% was depletion in VSCC (P < 0.01). Abnormalexpression of FHIT was significantly correlated with pathologicalgrade (P < 0.05). There was a significant difference between FHITdepletion and HPV infection based on the statistial analysis (P <0.05).CONCLUSION The FHIT depletion is related to occurrenceand development of VSCC, and the abnormal expression of FHITsignificantly correlates with HPV infection.

Use of Holmium:Yag laser in early stage oropharyngeal squamous cell cancer

AIM: To evaluate the efficacy of Holmium:Yag laser resection for oropharyngeal squamous cell cancer.METHODS: A prospectively collected case series of all patients with oropharyngeal squamous cell carcinoma undergoing laser resection using the Holmium:Yag laser technique only over a 15 year period at a tertiary referral centre. All patients underwent long term follow up with regular clinical and radiological surveillance, when indicated. All patients were operated on under general anaesthetic with a laser-safe endotracheal tube. Typically laser resection was performed first using an operating microscope, followed by neck dissection. The tumour was held with a Luc's forceps or Allis clamp. The Holmium:Yag laser was implemented via a fibre delivery system. The Holmium:Yag laser fibre, of 550 micron diameter, was inserted through a Zoellner sucker and attached via steri-strips to a second Zoellner suction to provide smoke evacuation. The settings were 1J/pulse, 15 Hz, 15 W in a continuous delivery modality via a foot pedal control. The procedure is simple, bloodless, effective and quick. All surgeries were performed as day cases. RESULTS: Twenty-seven oropharyngeal squamous cell cancer patients were identified, at the following subsites:23 lateral pharyngeal wall/tonsil, 2 anterior faucal and 2 tongue base. Of the 23 tonsil tumours,19 required no further treatment(83% therefore had negative histopathological margins) and 4 required chemoradiotherapy(17% were incompletely excised or had aggressive histopathological features such as discohesive, perineural spread, vascular invasion). The 2 patients with anterior faucal pillar neoplasia needed no further treatment. Both tongue base cancer cases required further treatment in the form of chemoradiotherapy(due to positive histopathological margins). Postoperatively, patients complained of pain locally, which resolved with regular analgesia. There were no postoperative haemorrhages. Swallowing and speech were normal after healing(10-14 d). There was one case of fistula when neck dissection was carried out simultaneously; this resolved with conservative management. All patients were followed up with serial imaging and clinical examination for a minimum of five years. Median follow up was 84 mo.CONCLUSION: Holmium:Yag lasers are a safe and effective treatment for Stage 1 and 2 squamous cell carcinoma of the oropharynx, excluding the tongue base.

Human papillomavirus DNA and P16～(INK4A) expression in concurrent esophageal and gastric cardia cancers

AIM:To investigate the relationship between human papillomavirus (HPV) infection and concurrent esophagus and gastric cardia cancer from the same patient (CC) and examine the significance of P16 INK4A protein expression.METHODS:Polymerase chain reaction was used to detect the presence of HPV type16 (HPV16).The expression of P16 INK4A protein was detected using immunohistochemistry.RESULTS:Among the CC specimens,HPV16-DNA was found in eight cases of esophageal squamous cell carcinoma (ESCC) and five cases of gastric cardia adenocarcinoma (GCA),respectively (47% vs 29%),and two of both ESCC and GCA.P16 INK4A was highly expressed in both ESCC and GCA.In the HPV-associated positive CC,higher P16 INK4A expression was observed in the GCA than in the ESCC (75% vs 25%,P < 0.05).CONCLUSION:HPV16 as a correlated risk factor may play an important role in the development of ESCC and GCA.P16 INK4A may be a screening index in the HPVassociated carcinoma of gastric cardia.

Relationships of early esophageal cancer with human papillomavirus and alcohol metabolism

BACKGROUND It is well known that an alcohol consumption habit together with inactive heterozygous aldehyde dehydrogenase-2(ALDH2)is an important risk factor for the development of esophageal squamous cell carcinoma(ESCC).It remains controversial whether human papillomavirus(HPV)infection contributes to the occurrence/development of ESCC.There has been no study in which the relationship between ESCC and HPV in addition to alcohol dehydrogenase-1B(ADH1B)and ALDH2 genotypes was evaluated.AIM To evaluate relationships between HPV infection and development of esophageal cancer,particularly early esophageal cancer,based on ADH1B/ALDH2 polymorphisms.METHODS We conducted an exploratory retrospective study using new specimens,and we enrolled 145 patients who underwent endoscopic resection for superficial ESCC and had been observed for more than two years by both physical examination and endoscopic examination in Hokkaido University Hospital.Saliva was collected to analyze genetic polymorphisms of ADH1B/ALDH2.We performed in situ hybridization for resected specimens to detect HPV by using an HPV type 16/18 probe.RESULTS HPV was detected in 15(10.3%)of the 145 patients with ESCC.HPV-positive rates in inactive ALDH2*1/*2 and ALDH2*1/*1+*2/*2 were 10.8%and 9.8%,respectively(P=1.00).HPV-positive rates in slow-metabolizing ADH1B*1/*1 and ADH1B*1/*2+*2/*2 were 12.0%and 10.0%,respectively(P=0.72).HPV-positive rates in the heavy or moderate alcohol consumption group and the light or rare consumption group were 11.1%and 8.7%,respectively(P=0.68).HPV-positive rates in the heavy smoking group and the light or no smoking group were 11.8%and 8.3%,respectively(P=0.59).The 3-year incidence rates of secondary ESCC or head and neck cancer after initial treatment in the HPV-positive and HPVnegative groups were 14.4%and 21.4%(P=0.22),respectively.CONCLUSION In the present situation,HPV status is considered to be less important than other risk factors,such as alcohol consumption,smoking habit,ADH1B/ALDH2 polymorphisms,and HPV status would therefore have no effect on ESCC risk management.

Detection of human papillomavirus in oropharyngeal squamous cell carcinoma

Worldwide there has been a significant increase in the incidence of oropharyngeal squamous cell carcinoma(OPSCC)etiologically attributed to oncogenic human papillomavirus(HPV).Reliable and accurate identification and detection tools are important as the incidence of HPV-related cancer is on the rise.Several HPV detection methods for OPSCC have been developed and each has its own advantages and disadvantages in regard to sensitivity,specificity,and technical difficulty.This review summarizes our current knowledge of molecular methods for detecting HPV in OPSCC,including HPV DNA/RNA polymerase chain reaction(PCR),loop-mediated isothermal amplification(LAMP),p16 immunohistochemistry(IHC),and DNA/RNA in situ hybridization(ISH)assays.This summary may facilitate the selection of a suitable method for detecting HPV infection,and therefore may help in the early diagnosis of HPV-related carcinoma to reduce its mortality,incidence,and morbidity.

Thedual pathogenesisofpenileneoplasia: The heterogeneous morphology of human papillomavirus-relatedtumors

Objective:Penile neoplasia,usually of squamous histogenesis,is currently classfied into human papillomavirus(HPV)-related or-dependent and non-HPV-related or-indepen dent.There are distinct morphological differences among the two groups.New research studies on penile cancer from Northern countries showed that the presence of HPV is corre lated with a better prognosis than virus negative people,while studies in Southern countries had not confirmed,perhaps due to differences in staging or treatment.Methods:We focused on the description of the HPV.related carcinomas of the penis.The approach was to describe common clinical features followed by the pathological features of each entity or subtype stressing the characteristics for differential diagnosis,HPV genotypes,and prognostic features of the invasive carcinomas.Similar structure was followed for penile intraepithelial neoplasia,except for prognosis because of the scant evidence available.Results:Most of HPV-related lesions can be straightforwardly recognized by routine hematoxylin and eosin stains,but in some cases surrogate p16 immunohistochemical staining or molecular methods such as in situ hybridization or polymerase chain reaction can be utilized.Currently,there are eight tumor invasive variants associated with HPV,as follows:basaloid,warty,warty-basaloid,papillary basaloid,clear cell,medullary,lymphoepithelioma-like,and giant condylomas with malignant transformation.Conclusion:This review presents and describes the heterogeneous clinical,morphological,and genatypic features of the HPV-related subtypes of invasive and non-invasive penile neoplasia.

Anal carcinoma-exploring the epidemiology,risk factors,pathophysiology,diagnosis,and treatment

Anal carcinoma is a relatively rare tumor that accounts for approximately 2%of gastrointestinal malignancies and less than 7%of anorectal cancers.Most anal tumors originate between the anorectal junction and the anal verge.Risk factors for the disease include human papillomavirus infection,human immunodeficiency virus,tobacco use,immunosuppression,female sex,and older age.The pathogenesis of anal carcinoma is believed to be linked to human papillomavirusrelated inflammation,leading to dysplasia and progression to cancer.Squamous cell carcinoma is the most common type of anal tumor,with an annual incidence of approximately 1 to 2 per 100000 persons.Treatment regarding anal cancer has emerged over time.However,chemoradiation therapy remains the mainstay approach for early localized disease.Patients with metastatic disease are treated with systemic therapy,and salvage surgery is reserved for disease recurrence following chemoradiation.This article aims to provide background information on the epidemiology,risk factors,pathology,diagnosis,and current trends in the management of anal cancer.Future directions are briefly discussed.

Research Progress on the Relationship Between Oral Microbial Community and Tumor

Significant progress was observed in studies of the relationship between oral Helicobacter pylori and gastric cancer and tumors. Based on three distinct and close relationships,namely, the relationship between oral H. pylori and gastric cancer, between oral microbial communities and oral squamous cell carcinoma, and between oral microbial communities of human immunodeficiency virus-infected patients and tumors, this work reviews the relationship between oral microbial communities and tumors. This research also provides reference for further analysis of the relationship between oral microorganisms and tumors to realize early diagnosis of tumor patients through detecting oral microorganisms under adjuvant therapy.

我国区域性宫颈鳞癌患者中HPV感染型别和年龄分布

目的回顾性探讨我国区域性宫颈鳞癌患者中人乳头瘤病毒(HPV)感染型别排序、年龄段分布、老年女性HPV感染特点及临床意义。方法收集1978年11月至2024年1月河南省信阳市商城县人民医院、南京中医药大学附属南京中医院、江苏省南京明基医院、南京同仁医院、南京市妇幼保健院等53家医院病理科的3101例病理组织学诊断为宫颈鳞癌的患者。从宫颈鳞癌石蜡组织中提取HPVDNA,采用聚合酶链式反应结合基因芯片法对3101例患者宫颈鳞癌组织进行23种HPV分型检测,并对HPV致癌风险型别的排序、≥60岁的老年女性和不同年龄段患者HPV型别分布情况进行分析。结果3101例宫颈鳞癌患者中检测出HPV感染者2879例(92.84%),其中单一型别的HPV感染者2460例(79.33%)。排名前8位单一型别高危HPV型别依次是16型、18型、58型、31型、33型、52型、59型、45型。其中16型感染人数比18型高(P<0.05),58型感染人数比31型明显增高(P<0.05),52型感染人数比59型明显增高(P<0.05)。40~49岁和50~59岁患者中患病人数、HPV感染人数、单一型别16型及18型感染人数均排名前两位。≥60岁的老年女性占宫颈鳞癌患者的30.44%。结论将HPV16、18、58型和HPV31、33、52、59型及其他HPV型别分别列为高风险、中风险和低风险致癌组,便于宫颈病变的分层管理。要重视对40~59岁年龄段女性的筛查工作,加强≥60岁老年女性宫颈鳞癌的筛查力度。