Correlation between Physical Status of Human Papilloma Virus and Cervical Carcinogenesis

The prevalence of human papilloma virus (HPV)-16 in patients with cervical cancer,the physical status of HPV-16 in patients with cervical lesions,and the role of HPV-16 integration in cervi-cal carcinogenesis were investigated.HPV genotyping was performed by using PCR approach with the primer GP5+/GP6+ and type-specific primer on biopsy specimens taken operatively from 198 women.Multiple PCR was done to detect physical status of HPV-16 in a series of cervical liquid-based cytology samples and biopsy specimens obtained from different cervical lesions with HPV-16 infection,includ-ing 112 specimens with cervical cancer,151 specimens with CINⅠ,246 specimens with CINⅡ and 120 specimens with CINⅢ.The results showed that there were 112 cervical cancer samples (56.57% of total cervical cancer patients) with HPV-16 infection.The frequency of HPV-16 pure integration was 65.18% (73/112),56.57% (47/120),23.58% (58/246) and 7.95% (12/151) in cervical cancer,CINⅢ,CINⅡand CINⅠ patients respectively.In situ hybridization was performed on some paraffin-embedded sections of CINⅡ,CINⅢ and cervical cancer to verify the physical status of HPV-16 infection.Sig-nificant difference was observed between cervical cancer and CINⅠ,CINⅡ,CINⅢ in the frequency of HPV-16 integration (P<0.01).It is suggested that HPV-16 is the most prevalent type and is associated with cervical cancer.In the case of HPV-16 infection there are close associations between the severity of cervical lesions and the frequency of HPV-16 integration.The application of testing HPV genotyping and physical status based on detection of HC-Ⅱ HPV DNA would be in favor of predicting the progno-sis of cervical precancerosis and enhancing the screening accuracy of cervical cancer.

Detection of Human Papilloma Virus Type 16 E6 mRNA in Laryngeal Squamous Cell Carcinoma by In Situ Hybridization

Objective：Laryngeal squamous cell carcinoma（LSCC） is a common malignant tumor in Northeast China and is frequently associated with well-established risk factors like smoking and alcohol abuse.Human papilloma virus（HPV） is an epitheliotropic oncogenic virus that has been detected in a variety of head and neck tumors including LSCC.This retrospective study was to investigate the prevalence of HPV infection in patients with LSCC.Methods：In situ hybridization was performed in 99 patients with LSCC to detect the expression of HPV-16 E6 mRNA.Results：The positive rate of HPV16 E6 mRNA was 36.36%（36/99） in laryngeal squamous cell carcinoma（LSCC）,whereas only 3 of 50（6%） specimens of the normal laryngeal mucosa as a control group showed positive results（P0.05）.Additionally,there was no corelation between HPV16 and age,gender,clinical stage,nodal status and tumor site（P0.05）.Conclusion：The results suggest that the increased prevalence of HPV infection compared to normal laryngeal mucosa and the fact that high-risk HPV types（especially type 16） were the most frequently identified do not allow the exclusion of HPV as a risk factor in laryngeal squamous cell carcinoma.However,their clinical value remains to be further investigated.

Detection of Human Papillomavirus DNA in Oral Cancer Tissue Using Polymerase Chain Reaction

Using polymerase chain reaction (PCR), 25 specimens from 22 patients with oral carcinomas were examined by 6 selected primers of human papillomavirus (HPV). Eighteen of the 22 patients (18/22) gave positive reaction with a positive rate of 81.8%. The positive rates of HPV 6, 11, 16 and 18 were 27.3%, 18.2%, 63.6% and 40.9% respectively. 13.6% positive for mixed infection of HPV 16 and 18 (3/22) and 18.2% positive for mixed infection of HPV, 6, 11, 16 and 18 (4/22). Examining enlarged cervical lymph nodes in three cases with suspecting metastases to cervical lymph nodes from oral carcinomas. It revealed HPV DNA 16 and 18 in two cases and HPV DNA 18 in one case. These results suggested that there was a tendency for HPV 16 and 18 to metastasinze via lymphatics. Only one case of the three had a pathologic diagnosis of lymph node metastasis. Of the 30 non tumor controls, HPV DNA positivity was 10%, all being HPV 18. χ 2 test gave a P<0.005. It strongly indicated that HPV 16 and 18 were related to oral carcinomas.

Studies on the correlation between human papilloma virus vaccine and premature ovarian failure

Cervical cancer is the most common malignant tumour of the female reproductive system,resulting in more than 500,000 new cases annually worldwide.In developing countries,cervical cancer ranks second in terms of cancer mortality among women.Human papilloma virus is the primary causative agent of cervical cancer,with approximately 70 percent of cervical cancers caused by high-risk types of human papilloma virus 16 and 18.There are currently three types of human papilloma virus vaccines available:bivalent,quadri-valent and nine-valent.However,in recent years,it is reported that cervical cancer vaccine can cause premature ovarian failure.Consequently,an extensive literature search to find out the correlation between human papilloma virus vaccine and premature ovarian failure became a priority.There is no sufficient evidence to support or prove that there is a link between the human papilloma virus vaccine and premature ovarian failure.Hence,the vaccine does not cause premature ovarian failure.

Squamous Papilloma:Case Report and Review of Literature

Squamous papillomas are common lesions of the oral mucosa with a predilection for the mucosa of the hard and soft palate. As an oral lesion,it raises concern because of its clinical appearance,which may mimic exophytic carcinoma,verrucous carcinoma or condyloma acuminatum. Its pathogenesis is related to human papilloma virus but there is controversy regarding its viral origin. We present a case of squamous papilloma presenting as oral lesion along with a review of the literature.

THE CERVIX MULTI－VIRUSES INFECTION AND THE DEVELOPMENT OF CERVICAL CARCINOMAS

The infections of human papilloma virus (HPV),herpes simplex virus type 2 (HSV-2) and Epstein-Barr virus (EBV) to human cervical epithelium are universal and some of them are associated with the development of cervical carcinomas. One hundred and eleven cervical cancer biopsies taken from Beijing area and Xiangyuan county in Shanxi province of China were examined for the presence of DNA sequences of HPV, HSV-2 and EBV by means of Dot blot hybridization. The experiment results showed that the total infectious rates of HPV, HSV-2 and EBV were 71.17% (79/111), 14.44%(16/111) and 15.63% (15/96), respectively. Seventy-nine samples positive for HPV were further analysed for the viral types distribution, the result indicated that the positive specimens of HPV type 16 accounted for 72.15%, otherwise, the biopsies positive for HPV type 18and 6B/11 only accounted for 16-46% and 11.39%,respectively. The data suggested that HPV infection,especially HPV type 16, may play an important role in the development of cervical carcinomas- 16 specimens positive for HSV-2 were examined for HPV DNAsequences and the result uncovered that 13 out of them were HPV16 positive (81.25%), 11 samples containing EBV genomes were also examined for HPV DNA sequences and the result indicated that 9 of 11 were detectable for HPV DNA. The experiment results proved a direct evtidence of multi-virus infection in cervix and of the synergistic interaction among viruses in the process of cervical epithelial carcinogenesis.Comparing of the viruses' infection of two areas, the frequencies of HPV infection in Beijing and Xiangyuan areas were 72.84% (59/ 81) and 66.67% (20/30) , the infectious rates of HSV-2 in the two areas were 8.64%(7/81) and 30% (9/30) (P<0.05), the rates of EBV infection in the two areas were 12.5% (10/80) and 31.25% (5/16)(0.1>P>0.05). The results proved another strong evidence that the high incidence of cervical cancer in Xiangyuan county may be closely correlated with multiviruses infection and with multi-virus synergistic interaction.

基于CiteSpace的人乳头瘤病毒疫苗相关研究热点及趋势分析

目的通过对公开发表的人乳头瘤病毒(human papilloma virus,HPV)疫苗相关文献的分析,了解HPV研究热点及趋势,为应用文献计量法分析各领域研究进展和方向提供参考。方法收集中国知网、万方数据库2012-2021年公开发表的HPV疫苗相关中文论文,根据纳入和排除标准纳入相关文献,用CiteSpace 6.1 R6进行作者合作网络、机构合作网络、关键词共现、关键词突发性探测、关键词聚类分析,绘制关键词时间线图。结果2012-2021年,HPV疫苗研究受到关注,相关文献数量整体呈上升趋势,研究热点在宫颈疾病,HPV基因分型及相应疫苗研制,疫苗认知、接种意愿及其影响因素。其中,2012-2014年,关注宫颈疾病、基因分型、预防性疫苗和治疗性疫苗的研究较多,2017-2018年,关注九价HPV疫苗的研究较多,2019-2021年,关注女大学生等特定人群的研究较多。通过关键词时间线图还发现,自2016年HPV疫苗在中国内地上市以后,除传统研究热点,相关研究开始关注HPV疫苗的卫生经济学评价,紧密结合当时的卫生政策背景和卫生热点,涉及医学伦理、心理学等多学科内容,且开始探索当下较为热门的研究方法,研究内容不断丰富和细化,内涵不断深化,外延持续拓展。结论考虑该类研究的与时俱进,未来研究可能会随着疫苗本身的发展,分层研究不同人群接种意愿,提升HPV疫苗覆盖率的接种策略,覆盖更多亚型的多价疫苗研制、效果、安全性、成本效益研究,HPV疫苗接种相关的真实世界研究,以及一系列疫苗推广和信息化等管理措施的效果评价。

人乳头瘤病毒多基因型检测对传统部分基因型宫颈癌筛查策略价值优化的敏感性分析

目的评估薄层液基细胞学检查(thinprep cytologic test,TCT)筛查技术的有效性、部分宫颈癌诊断费用和初始人群中人乳头瘤病毒(human papilloma virus,HPV)低度风险基因型感染者占比对HPV多基因型和HPV部分(16/18)基因型检测初筛策略的成本效果影响,为公共卫生决策部门选择宫颈癌筛查策略提供参考。方法基于构建的Markov队列模型,以预防宫颈癌发病例数为效果指标,模型运行50年,对HPV多基因型和HPV部分(16/18)基因型筛查方案进行敏感性分析,分析TCT筛查技术的有效性、部分宫颈癌诊断费用,以及初始人群中HPV低度风险基因型感染者占比的变化对成本效果的影响。结果在设定的模型及各参数阈值下,敏感性分析发现:HPV低度风险基因型(HPV 51/35/39/68/56/59/66型)感染者(HPV感染状况或进展为CIN1/2/3状况)中TCT分流检测的灵敏度与特异度[以TCT结果为不典型鳞状上皮细胞病变(atypical squamous cells of undetermined significance,ASCUS)以上为判别标准]变化对两种筛查策略差距影响较大;TCT检测费用、阴道镜检测费用及组织病理学检测费用对两种筛查策略差距影响相对较小。上述各指标在设定阈值范围内变化时,HPV多基因型与部分基因型策略相比,效果差异甚微,成本差异有所变化,具有成本优势。此外,随着初始人群中HPV低度风险基因型感染者的比例增大,HPV多基因型策略的优势亦逐渐增强。结论进一步明确HPV不同基因型的致病风险对优化多基因型HPV筛查的后续管理路径具有重要意义,而进一步细分TCT检测的TBS(The Bethesda System)分级报告结果,提升TCT检测精度则是保障多基因型HPV筛查防治策略价值优化的关键。

人乳头瘤病毒疫苗相关研究进展

使用人乳头瘤病毒(human papilloma virus,HPV)疫苗是提供针对HPV感染、尖锐湿疣和宫颈癌防护的一项有效策略。世界卫生组织在《加速消除宫颈癌全球战略》中指出,到2030年实现90%的女性在15岁前完成HPV疫苗接种的目标,因此,HPV疫苗相关研究是目前较为热点的问题。文章从HPV疫苗种类、免疫程序、疫苗效果、对免疫低下和已感染女性的保护作用、不良反应、认知和接种意愿以及卫生经济学分析等方面进行综述,介绍目前HPV疫苗的相关研究进展,以期为今后进一步研究提供参考和思路。

人乳头瘤病毒多基因型检测对传统部分基因型宫颈癌筛查策略的价值优化:基于Markov模型的分析

目的比较人乳头瘤病毒(human papilloma virus,HPV)多基因型(extended genotyping)与HPV部分(16/18)基因型检测技术对宫颈癌筛查策略及其后续管理的影响,分析可能带来的价值变化。方法基于Markov队列模型,以预防宫颈癌发病例数为效果指标,模拟100万名初始年龄为15岁的健康妇女在10、20、30、40、50年内从健康状态到宫颈癌发病的疾病进程,基于2种检测技术的宫颈癌筛查-诊断-癌前病变诊疗路径构建模型,分析2种筛查技术不同累计年份下的效果指标、阴道镜检查次数、宫颈上皮内瘤样病变(cervical intraepithelial neoplasia,CIN)1/2/3状态的筛查率,并比较成本与成本效果,以此判定对价值的影响。结果模型模拟10、20、30、40、50年,HPV多基因型相对于HPV部分(16/18)基因型在成本上分别减少29.73万、75.55万、98.53万、111.23万、119.39万元,效果始终保持一致,阴道镜检测次数可分别减少1002、2726、3865、4605、5086人次,CIN1-3筛查率上,模型运行第10、20、30、40、50年时,HPV多基因型策略分别减少约4%的CIN1-3的筛查率。结论相比于HPV部分(16/18)基因型,HPV多基因型检测技术在保障预防效果的情况下,能降低筛查假阳性带来的阴道镜“过诊”率,提升阴道镜检查精度,优化卫生资源利用效能,一定程度上避免假阳性带来的心理负担,从而优化传统HPV部分(16/18)基因型的筛查价值。

Female genital schistosomiasis,human papilloma virus infection,and cervical cancer in rural Madagascar:a cross sectional study

Background Women’s health in resource-limited settings can benefit from the integrated management of high-burden diseases,such as female genital schistosomiasis(FGS)and human papilloma virus(HPV)-related cervical cancer.In schistosomiasis-endemic countries such as Madagascar,data on FGS and HPV prevalence are lacking as well as preventive measures for both conditions.This study aims to estimate the prevalence of FGS and HPV in rural Madagascar,and to examine associated risk factors to identify opportunities for improving women’s health.Methods After initial community outreach activities,interested women aged 18-49 years were recruited consecutively in 2021 at three primary health care centers in the district of Marovoay.FGS was detected by colposcopy.Colposcopy images were double-blind reviewed by two independent specialists.A Luminex bead-based assay was performed on cervical vaginal lavage specimens for HPV typing.Crude(CPR)and adjusted prevalence ratios(APR)of associations between selected factors and FGS and HPV positivity were estimated using univariable and multivariable binary Poisson regression with 95%confidence intervals(CIs).Results Among 500 women enrolled,302 had complete information on FGS and HPV diagnosis,and were thus eligible for analysis.Within the sample,189(62.6%,95%CI:56.9-68.1)cases of FGS were detected.A total of 129 women(42.7%,95%CI:37.1-48.5)tested positive for HPV.In total,80 women(26.5%,95%CI:21.6-31.8)tested positive for both conditions.No association was observed between FGS and HPV positivity,while previous pregnancy(APR=0.65,95%CI:0.43-0.78)and older age(APR=0.59,95%CI:0.42-0.81)are showing a negative association with HPV infection compared to no previous pregnancy and younger age groups.Conclusions The results of the study show that FGS and HPV are highly prevalent in rural Madagascar.The concurrent prevalence of these two conditions requires urgent adaptations of public health strategies to improve women’s health,such as integrated services at primary level of care.

Revisiting HPV infection pattern among urban Indonesian women in general population and its implication on health burden:A cross-sectional analysis from Indonesian Noncommunicable Disease Research 2016

Objective:To identify circulating HPV types among urban Indonesian women and their specific co-infection patterns in bid to curb HPV infection in the general population and minimize its complications.Methods:Urban Indonesian women from general population were selected as sample framework.Sample size and distribution across regions were determined by the Indonesian Bureau of Statistics(Badan Pusat Statistik,BPS),which represented the national level.Up to 35408 cervical swab specimens were collected from August to September 2016 in 34 Indonesian provinces,categorized into six regions based on the development criteria set by the Ministry of National Development Planning(Badan Perencanaan Pembangunan Nasional,BAPPENAS).From all 1874 samples identified as HPV-positive,hybrid capture was implemented to evaluate type-specific HPV.This study analyzed descriptive data to determine the core-cluster of HPV combination.Co-occurrence HPV network was assessed using‘qgraph’package version 1.6.3 and computed in R version 3.6.3.Two-HPV association was analyzed in logistic regression using bias-reduction generalized linear model(brglm2)package version 0.5.1 adjusted by age and six main Indonesian regions.Results:The logistic regression analysis demonstrated that HPV type 52 had rare relationship despite its common co-occurrence,cementing its role in single HPV infection.HPV type 16 and 18 tended to form infection cluster and were strongly associated with other types.Conclusions:HPV type 52 was the most frequent HPV type among urban Indonesian women and accounted for most single infection cases.Concurrently,HPV 16 and HPV 18 accounted for most multiple infection cases and had strong tendency to attract other types,which may add further complications.However,due to lack of cytology and histological examination and information for other potential determinants,further in-depth studies are necessary to confirm whether these infection patterns truly connect to certain clinical outcomes.

Induction of SiHa Cells Apoptosis by Nanometer Realgar Suspension and Its Mechanism

The effects of nanometer realgar uterine cervix cancer cell line SiHa cells and suspension on proliferation and apoptosis of human oncogenic genes HPV16E6/E7 were investigated. A ＂micro-jet effiux＂ strategy was used for the preparation of nanometer realgar suspension. SiHa cells were treated with nanometer Realgar suspension in various concentrations （6.25, 12.5, 25 and 50 mg/L） for different durations （12, 24, 48 and 72 h）. The inhibitive effect of nanometer realgar suspension on growth of SiHa cells was detected by MTT method. Special morphological changes of apoptosis were observed by transmission electron microscopy （TEM） and DNA fragments electrophoresis. The apoptotic rate was quantified by flow cytometry （FCM）. The expression of HPV 16E6/E7 mRNA and protein was assayed by RT-PCR and Western blot respectively. The results showed after being treated with 25--50 mg/L nanometer realgar suspension for 48 h, the survival rate of SiHa cells was decreased, and apoptotic rate markedly increased in a time- and concentration-dependent manner. TEM and DNA electrophoresis revealed the special morphological changes of apoptosis. The apoptotic rate of SiHa cells treated with nanometer realgar suspension was significantly higher than in the control group （P〈0.01）, and G0/G1 phase arrest appeared following treatment with nanometer realgar suspension in 25 and 50 mg/L for 48 h. RT-PCR and Western blot assay indicated that nanometer realgar suspension reduced the HPV16E6/E7 gene expression. Nanometer realgar suspension could inhibit the proliferation and induce apoptosis of SiHa cells. The mechanism may be related to the down-regulation of the HPV16E6/E7 gene expression.

Clinical Observation of rhIL-2 Combined with Zhenqi Fuzheng and BaofuKang Suppository in the Treatment of Cervical Intraepithelial Neoplasia II with HPV Infection

Objective: To investigate the clinical effects of recombinant human interleukin-2 (rhIL-2) combined with Zhenqi Fuzheng and Baofukang on cervical intraepithelial neoplasia II (CINII) combined with human papilloma virus infection. Methods: There were 593 patients diagnosed with CINII with HPV infection, including 296 in the control group and 297 in the experimental group. The control group was given only Zhenqi Fuzheng oral and Baofukang suppository vaginal medicine. The experimental group was treated with rhIL-2 injection in addition to Zhenqi Fuzheng oral and Baofukang suppository vaginal medicine which is treated for 3 months. After 3 months, Thinprep cytologic test (TCT), human papilloma virus (HPV) quantitative examination and colposcopy biopsy were reviewed. Results: After 3 months of treatment, the negative conversion rate and total effective rate of HPV in the control group were 58.11% and 70.95% respectively, and the negative conversion rate and total effective rate of the experimental group were 79.46% and 90.57% respectively. There was significant difference between the two groups (p = 0.000). The curative rate of cervical lesions was significantly higher in the test group than in the control group, 89.56%, 68.91%, respectively. The statistical difference between the two groups is significant (p = 0.000). Conclusion: It has an essential clinical value that HPV infection patients and cervical intraepithelial neoplasia II associated with HPV infection patients are treated by rhIL-2 combined with Zhenqifuzheng and Baofukang, which is safe, effective, non-invasive, reusable advantages. However, the long-term efficacy and side effects need to be further studied.

Penile cancer:Updates in systemic therapy

Penile cancer is a rare genitourinary malignancy with a greater incidence in parts of Asia,South America,and Africa.Outcomes are very poor in patients with advanced disease and in those who do not respond to frstine mutimodal therapy.Among systemic therapy options,platinum-based chemotherapy is used in the frst line;however,approximately half of patients do not benefit.Response rates to systeric therapy as subsequent line treatment are historically dismal.There is also a paucity of prognostic and predictive tools within the context of penile cancer.As such,there remains an urgent need to expand systemic treatment options for patients with advanced penile cancer.The purpose of this review is to summarize the existing evidence for standard-of-care lines of systemic treatment,examine the potential of novel lines of systemic therapy,and provide an update as to the status of these new therapies within the context of penile cancer.

THE INFECTION OF EBV FOR CERVICAL EPITHELIUM-A NEW CAUSITIVE AGENT IN THE DEVELOPMENT OF CERVICAL CARCINOMAS?

Epstein-Barr virus was considered as a caustive agent for Burrkitt' s lymphoma and non-malignant B lymphocytes proliferation. The recent studies revealed the striking association of the Infection of EBV with the development of human epithelial tumors. 43 specimens of normal exfoliated cervical epithelial cells, 47 biopsies of chronic cervlcitis and 80 tissue samples of cervical carcinomas were tested for the presences of EBV W fragments by using dot blot hybridization method. The results showed that the detectable rates of EBV DNA sequences In the normal exfoliated epithelium, the chronic cervlcitis and cervical carcinomas were 44.16%, 12.77% and 13.75%, respectively. Eleven EBV positive DNA samples from cervical cancers were also examined for the presence of HPV DNA. The result showed 9 out of 11 were HPV DNA positive, the cultanious infectious rate of both viruses was about 81.81%.In this paper, the EBV genomes existed In the part of biopsies of cervical carcinomas were first reported. The results Implied that the development of cervical cancer might be associated with asymptomatic EBV Infection In early stage and might be the result from the synergistic carcinogenesis of EBV with other cervical oncovinises, especially with HPV.

Epidemiological studies of women under age 30 infectedwith human papillomavirus

The aim of this paper was to investigate the prevalence of human papilloma virus(HPV)infection in women under 30 years old with cervical intraepithelial neoplasia(CIN)or cervical cancer,in order to provide a basis for cervical cancer prevention and treatment.We recruited 2052 female cases from the education system in Futian District,Shenzhen city,from April 2006 to April 2008,with age ranging from 22 to 60 years old.Second-generation hybrid capture test was done for detection of female genital tract HPV and cervical colposcopy for screening CIN or cervical cancer.The prevalence of HPV and cervical precancerous lesions or cervical cancer was evaluated in different age groups of women.The HPV positive rate was 247/2052(12.00%),and 35/2052(1.71%)of the cases were≥CIN I by pathological diagnosis.In the 22–29-year-old age group,there were 291 cases,including 39 HPV-positive cases(13.40%)and one case of pathological diagnosis≥CIN I(0.34%),and there were 1761 cases in the 30–60-year-old age group,including 208 HPV-positive cases(11.81%)and 34 cases of pathological diagnosis≥CIN I(1.93%).The HPV-positive rate of 22–29-year-old age group was higher than that of 30–60-year-old age group,but the difference was not significant(χ2=0.5967,P=0.4398);the CIN and cervical cancer detection rate of the former group was lower than that of the latter one,and the difference was not significant either(χ2=3.7519,P=0.0527).The cases in 30–60-year-old age group were divided intofive age sub-groups,and the HPV-positive rate of the 22–29-year-old age group was compared with the remaining groups,and it was found that the HPV-positive rate of the former group(13.40%)was lower than that of the 40–44-year-old age group(14.70%)but higher than that of the other four groups.Moreover,the difference in the HPV-positive rate between the 22–29-year age group and the 50–60-year-old age group(6.06%)was significant(χ2=5.545,P=0.018),but the difference between the 22–29-year-old age group and each of the other four groups was not significant(P>0.05).In addition,the CIN and cervical cancer detection rate of the 22–29-year-old age group(0.34%)was lower than that of the remainingfive groups,and the difference between the 22–29-year-old age group and the 35–39-year-old age group(2.26%),and between 22–29-year-old age group and 40–44-year-old age group(2.30%)was significant(χ2=4.446,P=0.0035;χ2=4.525,P=0.0363,respectively),but the difference between the 22–29-year-old age group and each of other three groups was not significant(P>0.05).Furthermore,80.00%(28/35)cases of pathological diagnosis≥CIN I and 90.91%(10/11)lesions of pathological diagnosis≥CIN II occurred at 35–49 years of age.For many young women below the age of 30 who were infected with high-risk HPV were one-off infections,so it was not appropriate to recommend HPV detection as cervical precancerous lesions or cancer screening program for women less than 30 years old.The prevention and treatment of cervical cancer should be focused on those women more than 35 years of age.

The Economic Burden of Head and Neck Cancers in Denmark

Introduction: The incidence of head and neck cancers has increased markedly over the last decade. A Danish study of the costs of head and neck cancers has not been undertaken. Such studies have again become relevant due to the development of the HPV vaccines, as some cases are attributable to high-risk HPV 16 or 18. The objective of study was to estimate the incidence of head and neck cancers and their health care costs. Methods: Data on incidence and health care use related to head and neck cancer were obtained from Danish health care registers. New cancer patients were identified in the Danish National Cancer Register. Resource use per year in the hospital sector was estimated using data from the National Patient Register applying charges as cost estimates. Health care consumption by cancer patients was compared with that by an age- and sex-matched cohort without cancer. Results: We found that nearly 1000 new cases of oral cavity, oropharyngeal, hypopharyngeal and laryngeal cancer are diagnosed annually. In total the cost of these cancers to the Danish hospital sector constituted 31.6 million Euros per year, with the majority of costs (74%) occurring in men. The total costs associated with HPV16/18-related head and neck cancers were estimated to be 6.1 million Euros per year. Conclusion: This study provides the first Danish estimates of the costs associated with non-cervical and non-genital HPV-related cancers based on very reliable, individual-based data. It is expected that the current HPV vaccination programme will reduce this burden.

Update on Diagnosis and Management of Conjunctival Papilloma

Conjunctival papilloma is an acquired benign squamous cell tumor that can present at any age,but most frequently in the third and fourth decades of life.Papillomas have been associated with human papilloma virus(HPV)infection,usually types 6 and 11.Although histopathological diagnosis remains the gold standard,the advent of newer non-invasive imaging modalities such as optical coherence tomography(OCT)is transforming the way we diagnose and treat ocular surface tumors,including conjunctival papilloma.Management of these lesions can prove a challenge to the treating physician since not all lesions respond to medical and/or surgical therapy and in fact may worsen after surgical manipulation.In this review,the epidemiology,pathophysiology,clinical characteristics,and diagnosis of conjunctival papilloma including the use of OCT are discussed.Indications,efficacy,and side effects of currently available management options are also reviewed to guide the selection of the best treatment approach.

Roles of dysregulated Notch pathway and small DNA tumor viruses in cancer initiation and progression

Notch pathway is a major determinant of cell fate,and research within the last 30 years has shown dysfunctions within this pathway in the majority of solid tumors and leukemias.The molecular mechanisms causing aberrant expression of Notch in cancer are still partially known.Mesotheliomas,breast,and cervical cancers are among the cancer types for which the dysregulation of Notch has been reported together with the association of simian virus 40(SV40)or human papilloma virus(HPV)infections.In mesotheliomas and cervical cancer,there is clear evidence that these viruses cause and rely on dysregulation of the Notch pathway to promote and sustain cell transformation.The existence of a relationship in tumors between DNA viruses and Notch could have an impact on cancer therapy by implementing Notch inhibition to interfere with the growth of SV40-and HPV-positive cancers.In addition,since Notch links innate and acquired immunity and plays a key role in the regulation of the anti-viral response,targeting Notch in the presence of oncogenic viruses infections may help prevent the onset and progression of cancers associated with the exposure to these viruses.