High risk HPV types in southern Iranian patients with cervical cancer

This study was undertaken to assess the rate of HPV infection in cervical carcinoma among southern Iranian patients. 101 archival cervical carcinoma tissue samples of a 10 year period were studied for the presence of HPV DNA in southern Iran by a polymerase chain reaction method. In addition, the presence of high risk HPV-16 and HPV-18 genotypes was investigated. In total, 88 (87.1%) of the samples were HPV DNA positive, of which 83 were squamous cell carcinomas and 5 were adenocarcinomas. HPV-16 genotype was detected in 26.7% of HPV positive cervical carcinomas; however, none of the samples were positive for the existence of HPV-18 genotype. Collectively, these results suggest that HPV-16 and HPV-18 are not the frequent high risk HPV types in our patients and circulating HPV types in southern Iranian population are different from many other populations.     

HPV-based cervical cancer screening in a population at high risk for HIV infection

We determined the utility of an assay for 13 cancer-associated HPV types in primary cervical cancer screening of Zimbabwe women at high risk of HIV infection. HIV antibody status was determined by ELISA of oral mucosal specimens, and HPV DNA in the genital tract was identified by hybridization of cervical scrapes with probe B of Hybrid Capture II. Among the 466 women investigated, the prevalence of HPV, low-grade squamous intraepithelial lesions (LGSIL) and high-grade SIL (HGSIL) were 47.2%, 13.9% and 12%. Fifty-three and one-half percent of the women were HIV-seropositive. As compared with HIV-seronegative women, HIV-infected women had a greater than 2-fold HPV prevalence (64.3% vs. 27.6%), a greater than 7-fold amount of HPV DNA (RLU of 82.6 vs. 10.7) in HPV(+) women assessed as normal on the reference standard, and a nearly 3-fold greater HGSIL prevalence (17.3% vs. 5.9%). The strong link between HGSIL and HPV DNA positivity was seen in both HIV-infected and HIV-seronegative women. The amount of HPV DNA increased with disease severity in both HIV-seronegative and HIV-infected women. The sensitivity and specificity of the HPV test for HGSIL were, respectively, 90.7% (95% confidence limit 77.9-97.4%) and 41.3% (34.5-48.3%) in HIV-infected women and 61.5% (31.6-86.1%) and 74.5% (68.0-80.3%), respectively, in HIV(-) women. The usefulness of the HPV test as a screening test for cervical cancer in areas of high HPV prevalence will depend upon local health resource availability, disease priorities and policies regarding clinical case management.     

人乳头瘤病毒分型检测在宫颈癌及癌前病变防治中的应用

人乳头瘤病毒(HPV)与宫颈癌及宫颈癌前病变的发生密切相关,并且HPV亚型不同,其致癌力、宫颈癌病理分型以及宫颈癌的预后均有所不同.早期发现官颈高危型HPV感染与准确分型,及时进行早期干预治疗,是提高宫颈癌防治效果的有效途径,临床HPV分型检测对宫颈癌及癌前病变的防治有重要意义.     

Evolution of precancerous lesions in a rural Chinese population at high risk of gastric cancer.

The pathogenesis of gastric cancer (GC), particularly of the intestinal type, is thought to involve a multistep and multifactorial process. Our objective was to determine the rates of transition from early to advanced gastric lesions in a population in Linqu County, China, where the GC rates are among the highest in the world. An endoscopic screening survey was launched in 1989-1990 among 3,399 residents aged 34-64 years with precancerous lesions diagnosed from biopsies taken from 7 standard locations in the stomach and from any suspicious sites. The cohort was subsequently followed, with endoscopic and histopathologic examinations conducted in 1994. Logistic regression analysis was used to estimate odds ratios (ORs) of progression to advanced lesions of various levels of severity as a function of age, sex and baseline pathology. The rates of progression were higher among older subjects, among men and among subjects with more extensive gastric lesions. 34 incident GCs were identified during the follow-up period. The ORs of GC, adjusted for age and sex, varied from 17.1, for those with baseline diagnoses of superficial intestinal metaplasia (IM), to 29.3, for those with deep IM or mild dysplasia (DYS) or IM with glandular atrophy and neck hyperplasia, to 104.2, for those with moderate or severe DYS, as compared with subjects with superficial gastritis (SG) or chronic atrophic gastritis (CAG) at baseline. Our prospective study of a high-risk population revealed sharp increases in the risk of GC and advanced precursor lesions according to the severity of lesions diagnosed at the start of follow-up. Int. J. Cancer, 83:615-619, 1999. Published 1999 Wiley-Liss, Inc.     

Risk factors of precancerous gastric lesions in a population at high risk of gastric cancer

Objective|  

In cancer prevention, the targeting of precancerous lesions has been recognized as the most promising method. However, little attention has been paid to the risk factors of precancerous gastric lesions, especially in rural China where there is high prevalence of precancerous gastric lesions. We therefore conducted a cross-sectional study in Liaoning province, China, to investigate the potential risk and protective factors of these precancerous gastric lesions.     

Comparison studies of HPV detection in areas at different risk for cervical cancer.

The hypothesis of a geographical correlation between HPV detection rates and incidence of cervical cancer has been investigated in studies of various types. However, results from these studies are equivocal, in contrast to findings concerning other suspected risk factors which seem to correlate well with the cervical cancer incidence. Possible explanations include (1) greater sensitivity of ecological studies to cumulative exposures such as lifetime number of sexual partners, lifetime smoking and seroprevalence of herpes simplex virus type 2, than to HPV DNA prevalence which does not reflect cumulative exposure to HPV and (2) misclassification in the HPV diagnosis leading to wrong prevalence estimates. In future research, it will be important to establish the sensitivity and specificity of the different methods and conduct intra- and interlaboratory validation studies in order to standardize methods. In spite of the limitations of cross-sectional studies, the measurement of HPV prevalence and its correlation with, for example, sexual behaviour is still valuable for our understanding and interpretation of the role of HPV infections.     

Lewis antigen alterations in a population at high risk of stomach cancer.

Anomalous Lewis(a) antigen and sulfomucin expression are considered as markers of progression in precursor lesions of gastric cancer. Additionally, Lewis antigen and secretor phenotype have been related to Helicobacter pylori infection and gastric epithelial damage. The two objectives of this study were to correlate Lewis antigen alterations with histochemical changes and to explore the relationship between Lewis and secretor phenotypes and gastric epithelial damage related to H. pylori infection. The study subjects were selected from a chemoprevention trial in Tachira State, Venezuela, an area with a high risk of gastric cancer. Anomalous Lewis(a) antigen expression in Lewis (a-b+) phenotype individuals was closely related to the severity of the histological lesions, especially to dysplasia and type III intestinal metaplasia lesions. A weak relationship was observed between nonsecretor individuals and more advanced lesions of IM, but this association was not statistically significant. There was no relationship between secretor phenotype and H. pylori status, atrophy, regenerative activity, erosion, or ulcer.     

HPV不同亚型在宫颈癌前病变及宫颈癌中的分布情况

目的:探讨HPV不同亚型在宫颈癌前病变及宫颈癌中的分布情况。方法:选取我院于2015年1月至2017年1月期间收治的124例宫颈癌患者和宫颈癌前病变患者,其中宫颈癌患者有36例,宫颈癌前病变患者有88例。对所有入选患者的宫颈脱落细胞进行采集,并且进行人乳头瘤病毒检测,观察分析HPV不同亚型在宫颈癌前病变及宫颈癌中的分布情况。结果:共有89例（71.77%）患者检测出HPV阳性,其中宫颈癌患者的阳性检出率为100%,显著高于癌前病变患者中的阳性检出率60.23%（P＜0.05）。宫颈癌患者中HPV18和HPV16亚型的感染率最高,分别为44.44%和47.22%;在88例宫颈癌前病变患者中,低级别型患者的HPV33和HPV52、HPV16亚型感染率最高,分别为9.68%和32.36%、32.36%;高级别型患者的HPV58、HPV52、HPV18、HPV16亚型感染率最高,分别为13.64%、13.64%、22.73%、31.82%。89例HPV感染患者中有9例患者出现多重感染,多重感染率为10.11%,其中三重及以上感染率为3.37%。所有宫颈癌HPV感染患者均为单一感染;癌前病变患者中低级别多重感染率为9.68%,高级别多重感染率为27.27%。结论:宫颈癌患者和宫颈癌前病变患者中均以HPV16和HPV18亚型感染率较高,此外宫颈癌前病变患者中的HPV58和HPV52亚型患者也具有较高的感染率;临床上使用HPV感染检测并针对HPV的综合治疗能够有效预防和控制宫颈癌及其癌前病变的发生,值得广泛推广运用。     

TP53 polymorphism, HPV infection, and risk of cervical cancer.

The role of a polymorphism at position 72 of the tumor suppressor gene TP53 in the development of cervical cancer is not well established. The arginine variant of the p53 protein could be more susceptible to degradation by human papillomavirus (HPV) E6 protein than the protein containing proline. Recent studies show controversial results. We investigated a possible association between TP53 polymorphism and cervical cancer in a Peruvian population with high prevalence of HPV infection. HPV status and TP53 polymorphism were determined for 119 cases of invasive cervical cancer and 127 control women from Peru. HPV infection was detected by PCR of cervical cells or tumor biopsies. For determination of TP53 polymorphism, exon 4 of the TP53 gene was amplified by PCR, and DNA was subsequently subjected to restriction enzyme digest. Associations between TP53 polymorphism, HPV infection, and cervical cancer were assessed using logistic regression. Women homozygotes for arginine had a 2.2-fold increased risk (95% confidence interval: 0.6-7.6) for cervical cancer. The odds ratio for women heterozygotes for Arg/Pro was 3.5 (95% confidence interval: 0.9-14). Similarly increased risks were found when restricting analysis to HPV-positive women only. The distribution of TP53 genotypes in this Peruvian population was comparable with that found in Caucasians. Our results cannot rule out an association between the TP53 polymorphism at codon 72, HPV infection, and the etiology of cervical cancer.     

高危型人乳头状瘤病毒的病毒负荷量与宫颈癌及宫颈上皮内瘤变的关系

目的探讨高危型人乳头状瘤病毒(HPV)的病毒负荷量与宫颈癌及宫颈上皮内瘤变(CIN)的相关性。方法选取2013年6月至2016年6月间北京市健宫医院收治的1056例行宫颈癌筛查的患者,对高危型HPV的脱氧核糖核酸(DNA)行第2代杂交捕获试验(HC-Ⅱ)半定量检测,予以受试者工作特征曲线(ROC曲线)分析,对CINⅡ及以上宫颈病变理想RLU/CO界值进行判定。结果慢性宫颈炎592例(56.1%);CIN395例(37.4%),CINI级110例(10.4%),CINⅡ~Ⅲ级285例(27.0%);宫颈癌69例(6.5%)。高危型HPV病毒负荷量随着宫颈病变程度的加深而增高,差异有统计学意义(P<0.05)。慢性宫颈炎、CINI级、CINⅡ~Ⅲ级及宫颈癌患者高危HPV-DNA病毒负荷量中位数分别为33.24、58.37、103.48和172.56。ROC曲线分析,预测CINⅡ级及以上宫颈病变的最佳RLU/CO值为3.173,其灵敏度和特异度分别为89.0%和58.0%,Youden指数为0.587。结论高危型HPV病毒负荷量与宫颈癌及前期病变有着显著的相关性,会随着病情严重程度的加深而增加,预测CINⅡ及以上宫颈病变高危HPV最佳负荷量值为3.173。     

Comparison of HPV type distribution in high-grade cervical lesions and cervical cancer: a meta-analysis

Particular types of human papillomavirus (HPV) infection may preferentially progress from high-grade squamous intraepithelial lesions (HSIL) to squamous cell carcinoma of the cervix (SCC). We performed a meta-analysis of published data to compare HPV type distribution in HSIL and SCC. HPV16, 18 and 45 were each more prevalent in SCC than HSIL, whereas the reverse was true for other oncogenic types including HPV31, 33, 52 and 58. These data suggest that HSILs infected with HPV16, 18 and 45 preferentially progress to SCC. This may have implications for follow-up protocols of future HPV-based cervical cancer screening programmes and for HPV vaccine trials.     

Different outcome of invasive cervical cancer associated with high‐risk versus intermediate‐risk HPV genotype

Human papillomavirus (HPV) DNA sequences are associated with the large majority of invasive cervical carcinoma but the role of specific genotype(s) in the outcome of the disease is still debated. To determine the viral epidemiology in the French population of patients and the prognostic value of HPV genotypes in cervical cancer, we performed a retrospective study in 515 patients treated in our Institution from 1985 to 2005. Ninety‐six percent of the cases were found associated with HPV DNA whereas 4% remained HPV negative. High‐risk HPV 16/18 genotypes were found in 70% of the cases. HPV 18 was more frequently associated with adenocarcinoma (40.6%) than HPV 16 (10.4%) and found in tumours developed in younger women (mean age, 45.8 years) than HPV 16 (48.3 years) or other HPV types (53.6 years). In multivariate analysis, node involvement (p < 0.0001), parametria invasion (p = 0.009), tumour size (p = 0.01) and HPV status (p = 0.02) were associated with disease‐free survival (median follow‐up 95 months). Disease outcome was better in tumours associated with intermediate risk HPV types (HPV 31, 33, 35, 39, 52, 53, 58, 59, 73) than in tumours with high oncogenic types (HPV 16, 18, 45) (p = 0.03). Node status and tumour size remained prognostic factor for overall survival. Our data show that HPV genotype is one of the biological factors associated with the outcome of cervical cancer. One third of invasive carcinoma were not associated with HPV 16/18, indicating that the screening for cervical neoplasia should be maintained after prophylactic vaccination against these HPV genotypes. © 2008 Wiley‐Liss, Inc.     

Angiogenic squamous dysplasia in bronchi of individuals at high risk for lung cancer.

Lung carcinogenesis is assumed to be a multistep process, but detailed understanding of the sequential morphological and molecular changes preceding invasive lung cancer remains elusive. To better understand early lung carcinogenesis, we initiated a program of fluorescence bronchoscopy in smokers at high risk for lung cancer. In the bronchial biopsies from these subjects, we observed a unique lesion consisting of capillary blood vessels closely juxtaposed to and projecting into metaplastic or dysplastic squamous bronchial epithelium, angiogenic squamous dysplasia (ASD). Serial sections of the capillary projections confirmed that they represent intramucosal capillary loops. Microvessel density in ASD was elevated in comparison to normal mucosa (P = 0.0003) but not in comparison to other forms of hyperplasia or dysplasia. ASD thus represents a qualitatively distinct form of angiogenesis in which there is architectural rearrangement of the capillary microvasculature. Genetic analysis of surface epithelium in a random subset of lesions revealed loss of heterozygosity at chromosome 3p in 53% of ASD lesions. No confirmed p53 mutations were identified. Compared with normal epithelium, proliferative activity was markedly elevated in ASD lesions. ASD occurred in 54 of 158 (34%) high-risk smokers without carcinoma and in 6 of 10 patients with squamous carcinoma who underwent fluorescence bronchoscopy. One early-stage invasive carcinoma was noteworthy for the occurrence of ASD juxtaposed to invasive tumor. Seventy-seven (59%) of the ASD lesions were detected by abnormal fluorescence alone. Twenty bronchial sites (11 patients) were rebiopsied 1 year after the initial diagnosis. At nine (45%) of these sites, the lesion was found to persist. The lesion was not present in biopsies from 16 normal nonsmoker control subjects. The presence of this lesion in high-risk smokers suggests that aberrant patterns of microvascularization may occur at an early stage of bronchial carcinogenesis.     

The influence of smoking and other cofactors on the time to onset to cervical cancer in a southern European population.

Cervical cancer is a complex and multifactorial disease. Although there are substantial data supporting the causative role of persistent human papillomavirus (HPV) infection in the development of cervical cancer, the complete course of the disease has never been completely understood. Several risk cofactors have been suggested with controversial results. Portugal has the highest incidence of squamous cell carcinoma (SCC) within western Europe and there are no known studies regarding the role of cofactors in SCC. The aim of our study was to evaluate the role of smoking, sexual behaviour, reproductive and contraceptive history, in the time-to-onset (TTO) of severe cervical lesions (HGSIL/SCC) in the Portuguese population. We verified that age of first sexual intercourse under 18 years (odds ratio (OR) 2.8), pregnancy (OR 2.9), first pregnancy under 21 years (2.6), number of pregnancies (OR 2.3-5.4) and parity (OR 1.9-5.7) are risk factors in the development of cervical neoplasia. Smoke exposure index (SEI) was significantly different (P=0.002) between cases and controls. Our results regarding time-to-onset demonstrate that smoking (P<0.001, log rank test), number of sexual partners (P<0.001, log rank test) and use of oral contraceptives (P<0.001, log rank test) are important determinants in the earlier onset of severe cervical lesions. Using this approach, our findings may help to clarify the role of smoking and other cofactors in the persistence and progression of cervical lesions.     

宫颈 TCT 异常患者行 HPV 检测在宫颈病变诊断中的临床价值

目的：探讨薄层液基细胞学检查（TCT）异常的患者行人乳头状瘤病毒（HPV）检测在宫颈癌及癌前病变诊断中的临床价值。方法：2010年3月至2012年3月在汉川市人民医院妇科门诊就诊的患者共计2389例行液基细胞学检查,结果异常的有526例患者,同时进行HPVDNA检测和阴道镜下宫颈活检,以组织病理学结果作为诊断的金标准。结果：宫颈活检组织病理学诊断结果：526例患者中宫颈炎及CINI456例,占86．69％,CINIl34例,占6．46％,CINⅢ32例,占6．08％,宫颈浸润癌4例,占0．76％。HPVDNA检测阳性者共有226例,阳性率随病变严重程度的增加而增加。CINII级及其以上病变检出率在HPVDNA检测阳性组中明显高于阴性组中,两组比较有显著性差异（P〈0．05）。结论：细胞学检查结果异常的患者,病理组织学检查结果相差较大,可以从宫颈炎症到宫颈癌。HPVDNA检测可以减少单纯应用薄层液基细胞学而造成的宫颈病变漏诊率,并对细胞学结果有进一步的分流作用。     

HLA-B alleles, high-risk HPV infection and risk for cervical neoplasia in southern Chinese women

A population-based study was conducted on 256 southern Chinese with cervical intraepithelial neoplasia grade III (CIN III) or invasive cervical cancer (ICC) and on 258 controls to examine the associations between HLA-B alleles, infection with high-risk human papillomaviruses (HPVs) and the development of cervical neoplasia. HLA-B15 was found to be protective for CIN III/ICC overall (p(corrected) = 0.003), and for HPV52-positive CIN III/ICC (p(corrected) = 0.003). A marginal protective effect of B15 was observed for HPV16-positive CIN III/ICC, but no significant associations were revealed for HPV18- or HPV58-positive cases. None of the HLA-B alleles were found to confer an increased risk for cervical neoplasia. HLA-B15 is common among Asian for whom HPV52, a worldwide uncommon HPV type, also exists in a relatively high prevalence. It would also be worthwhile to assess the association between HLA-B15, HPV52 and cervical cancer in other Asian populations.     

A study of precancerous gastric lesions in a high risk population

A study of precancerous gastric lesion was conducted in a randomly selected high risk population in Linqu, Shandong Province of China. 849 subjects aged from 30–64 were examined bioptically. There were 8 cases of gastric cancer, the prevalence rate was 0.9%. 169 subjects were diagnosed to be dysplasia, the prevalence rate of dysplasia was increased significantly with age. The regression equation was Y=0.47X?0.25. The prevalence of CAG was found in 36 per cent of the studied subjects and both dysplasia and CAG were more serious in the antrum than the fundus. The results showed a natural history of precancerous gastric lesions in a high risk population in a high risk area.     

Cervical screening, high-grade squamous lesions, and cervical cancer in illicit drug users

Background and purpose

Women who use illicit drugs (“drug users”) are exposed to human papillomaviruses (HPVs) from lifestyle risks that include sex risk behaviors, human immunodeficiency virus infection, and high levels of tobacco smoking. Both HPVs and tobacco smoking are recognized causes of cervical cancer, but little is known about risk in drug users. We sought to examine risk of cervical neoplasia and to estimate cervical screening prevalence in drug users compared to non-drug-users in Australia.

Methods

Our study linked hospital admission records of women aged 20–54 in 2000–2007 to Pap Test Register and Cancer Registry records for 19,699 with an illicit drug–related admission and 194,089 without. We designed a nested case–control study of risk of cervical intraepithelial neoplasia (CIN) 2/3 and cervical cancer and a cross-sectional study of screening prevalence in this cohort of women.

Results

Drug users were less likely than non-users to be screened in the past 3 years (crude prevalence 47 vs 58 %; prevalence ratio 0.80; 95 % CI 0.78–0.81). Odds ratios (ORs) in drug users, adjusted for cervical screening history and smoking, were 1.13 (95 % CI 1.04–1.23) for CIN 2/3 and 1.43 (95 % CI 0.96–2.15) for cervical cancer. The adjusted ORs in each case were similar in cannabinoid users and users of other drugs.

Conclusions

The increased risks of CIN 2/3 and cervical cancer we observed are probably due to sex risk behaviors and their associated high risk of HPV. Interventions in drug users, such as HPV vaccination and barrier contraception and more cervical screening, might reduce the risk of cervical neoplasia.