Truscreen联合HPV-DNA分型检测在宫颈病变筛查中的作用

目的:探讨应用宫颈癌筛查系统初善仪()(TruScreen())与HPV分型检测时宫颈病变的诊断价值.方法:对80例LCT≥ASC的患者依次进行TruScreen检查、HPV分型检测和阴道镜下宫颈活检,将病理结果与TruScreen和HPV结果对照分析.结果:TruScreen和HPV阳性分别为52例和41例,病理学检查阳性为38例.TruScreen、HPV检测CIN的敏感度分别为94.73%、81.58%,特异度分别为61.90%、76.19%,差异有显著性(P<0.05),两种检查的符合率:71.25%.联合检查对高度CIN诊断的敏感度为100%.HPV16、58感染较多出现在高度CIN中.结论:TruScreen可即时检测宫颈病变,敏感度高,联合HPV分型检测对宫颈癌及癌前病变的筛选及预后判断有重要意义.     

PCR-RFLP and FTIR-based detection of high-risk human papilloma virus for cervical cancer screening and prevention

BackgroundApproximately 70% of cervical carcinoma cases show the presence of high-risk Human Papilloma Virus (HPV), especially HPV-16 and HPV-18, and can be used to stratify high risk patients from low risk and healthy. Currently, molecular biology techniques such as polymerase chain reaction (PCR) are used to identify the presence of virus in patient samples. While the methodology is highly sensitive, it is labor intensive and time-consuming. Alternative techniques, such as vibrational spectroscopy, has been suggested as a possible rapid alternative. Therefore, in this study, we evaluate the efficiency of cervical fluid Fourier Transform Infrared spectroscopy (FTIR) in patient risk stratification informed by PCR.MethodsCervical fluid samples (n = 91) were obtained from patients who have undergone routine Papanicolaou (Pap) test. Viral genome was identified and classified as high/low-risk by PCR-Restriction Fragment Length Polymorphism (PCR-RFLP). FTIR spectra were acquired from samples identified by PCR-RFLP as No-HPV (n = 10), high-risk HPV (n = 7), and low-risk HPV (n = 7).ResultsOf the 91 samples, was detected the viral genome by PCR in 36 samples. Of these 36 samples, nine samples were identified to contain high-risk HPV (HR-HPV) and nine samples were found to have low-risk HPV (LR-HPV). The FTIR spectra acquired from No-HPV, LR-HPV, and HR-HPV showed differences in 1069, 1437, 1555, 1647, 2840, 2919, and 3287 cm^-1 bands. Principal Component Analysis (PCA) showed distinct clusters for No-HPV and HR-HPV and No-HPV and LR-HPV, but there was significant overlap in the clusters of HR-HPV and LR-HPV. PCA-Linear Discriminant Analysis (PC-LDA) after Leave One Out Cross Validation (LOOCV) classified No-HPV from HR-HPV and No-HPV from LR-HPV with 100% efficiency in the 1400-1800 cm^-1 spectral range. LOOCV classifications for LR-HPV and HR-HPV from each other were 71 and 75%, respectively, in the 2800-3400 cm^-1 spectral range.ConclusionsThe results highlight the high sensitivity of PCR-RFLP in HPV identification and show that FTIR can classify samples identified as healthy, low, and high-risk samples by PCR-RFLP.General significanceWe show the possibility of using FTIR for initial cervical cancer risk stratification followed by detailed PCR-RFLP investigations for suspect cases.     

Cost effectiveness of population screening and rescreening for cervical cancer in the Netherlands

In a screening program for cervical cancer held in the western part of the Netherlands in 1978, it was shown that the incidence of positive cases dropped from 8.0% to 1.4% when repeat screening was performed within two years; however, the incidence of mild dysplasia remained the same (13.0%). Forty percent of the allocated funds were used for canvassing. Recanvassing of the no-response group did not result in the finding of positive cases. Of the ten positive cases in the rescreened group, four had had inadequate negative smears previously, and two had had adequate negative smears; in two cases the previous smears were reclassified as dysplasias, and in the two remaining cases endocervical carcinoma cells were found in the additional endocervical smear. In light of the high canvassing costs of population screening and the low detection rate of positive cases in the rescreened group, as described in this paper, it appears overly costly to repeat population screening with two years.     

子宫颈癌预防用人乳头瘤病毒疫苗及其展拓

人乳头瘤病毒(HPV)是人子宫颈癌病原体,这一发现奠定了子宫颈癌预防用人乳头瘤病毒疫苗得以问世的科学基础。临床实践证明,默克(Merck)公司的Gardasil和葛兰素史克(GSK)公司的Cervarix这两种疫苗可预防由HPV16和HPV18引起的子宫颈癌,有效率几乎达100%。Gardasil和Cervarix的成功激动了围绕Gardasil和Cervar-ix的展拓研究。     

HPV检测早期筛查宫颈癌的临床意义——附妇科门诊2761例宫颈拭子HPV分析

目的探讨女性HPV DNA检测在宫颈癌防治方面的意义。方法应用DNA杂交技术对2 761例妇科门诊就诊者基因分型检测。结果 2 761例样本中,HPV感染有768例,阳性率27.82%,HPV感染人次972人次。检测高危型HPV（16,18,31,33,35,39,45,51,52,56,58,59,68）813人次,占感染总人次的83.64%;检出低危型HPV（6,11,42,43,44）73人次,占感染总人次7.51%;中国人群常见型HPV（53,66,CP8304）86人次,占感染总人次的8.85%。165例样本中包含了25种亚型的感染。结论 DNA杂交技术检测HPV基因分型,可一次检测多种亚型,有利于对HPV多重感染的诊断和宫颈癌的防治,可作为宫颈癌筛查的手段。     

Cost effectiveness of biofeedback and behavioral medicine treatments: a review of the literature

This paper reviews multicomponent behavioral medicine studies that contain cost-effectiveness and or cost-benefit data relevant to the field of biofeedback and relaxation training, primarily when assisted by biofeedback, with or without stress management, in the treatment of psychosomatic illness and pain. A model for evaluating biofeedback treatment is presented. Cost-effectiveness data concerning reduction in physician visits and/or medication use, decrease in medical care costs to patients, reduction in hospital stays and rehospitalization, reduction of mortality, and enhanced quality of life are reviewed. Evidence suggests that multicomponent behavioral medicine treatments are cost-effective on all dimensions reviewed. Cost/benefit ratios range between 1:2 and 1:5, with a median of 1:4. Evidence that could increase the cost effectiveness of biofeedback is reviewed.     

HPV testing for cervical cancer screening in Croatia

Opportunistic screening based on the Pap smear has been undertaken in Croatia since 1953. However, cervical cancer remains an important health problem in Croatia when compared to European countries with organised screening programmes. In Croatia, in addition to screening based on well established cytology, Human papillomavirus (HPV) testing is widely used as secondary test as a triage to borderline cytology and as a follow-up after treatment of severe cervical lesions. Many different approaches for HPV testing arose in Croatia over the last decade depending on the needs of each medical institution involved. Presently, there is an urgent need for better networking between the laboratories, the implementation of quality assessment and the adaptation of a uniform system of referring to and reporting of HPV testing. In conclusion, the best possible organisation for HPV testing would be essential for implementation of HPV testing as primary screening test in Croatia, an thus ultimately and hopefully, the more successful cervical cancer control.     

Some novel adenosine mimics: synthesis and anticancer potential against cervical cancer caused by human papilloma virus

Two novel adenosine analogs, viz. 9-(1'-beta-D-arabinofuranosyl)-6-nitro-1,3-dideazapurine or Ara-NDDP (1) and 9-(5'-deoxy-5'-S-(propionic acid) (1'-beta-D-ribofuranosyl) adenine or SAH analog (2), indigenously synthesized, have been found to be potential anticancer agents against cervical cancer caused by human papilloma virus.     

Primary HPV testing: a proposal for co‐testing in initial rounds of screening to optimise sensitivity of cervical cancer screening

As explained by Kitchener in a previous issue of Cytopathology (2015; 26 :4‐6), primary human papillomavirus (HPV) testing is likely to be introduced in the UK for all women aged 25–64 years following pilot site studies already in place. This will be necessary when the prevalence of cervical cancer and its precursors declines when vaccination takes effect but there is a risk in abandoning cytology as a primary test: a risk that would be most apparent in the present unvaccinated population in which the prevalence of cervical cancer and its precursors is exceptionally high. HPV testing is more sensitive than cytology but has a significant false‐negative rate that could be detrimental to a successful screening programme if introduced without cytology backup. Accurate cytology would be needed for triage and could be compromised if HPV‐negative tests were excluded from examination. This article proposes a compromise: cytology and HPV co‐testing for the first two screening tests to optimise the sensitivity of the test as a whole. Registrations of invasive and in situ carcinoma of the uterine cervix in England indicate that the prevalence of the disease is highest in young women in the early rounds of screening. Calculations of the likely impact on the workload of this proposal have been based on a service evaluation of 295 cytology tests received at St Thomas’ Hospital, which suggests that the volume of cytology tests would be reduced by approximately 60% compared with 80% for primary HPV testing alone. This proposal should be debated openly before irrevocable changes are made to a skilled workforce.     

Sun exposure, sexual behavior and uterine cervical human papilloma virus

Introduction We have previously observed marked seasonal fluctuations in the frequency of cervical smears positive for human papilloma virus (HPV) in a series of smears obtained in Holland, with a peak in the summer months, especially August. Here, we tested two possible mechanisms that might underlie this summer peak: (1) enhanced transmission of HPV due to increased seasonal sexual activity, or (2) suppression of immunity due to summertime population exposure to solar ultraviolet (UV) radiation. Methods Data derived from a continuous series of >900,000 independent cervical smears obtained from 1983 to 1998 were assessed for histopathologic epithelial changes pathognomonic of HPV. The rate of HPV positivity was then compared to both the rate of sexual activity (using conception frequency as a readily available surrogate) as well as yearly and monthly fluctuations in solar-UV fluency. Results The rate of HPV positivity was found to be twice as high during the summer months, with a peak in August corresponding with maximal UV fluency. Furthermore, over these 16 consecutive years of continuous observation, maximum HPV detection rate and maximum UV fluency are positively correlated (r=0.59, P<0.01); the sunnier the year, the greater the rate of HPV. Likewise, there is a positive correlation of the monthly UV fluency, and monthly HPV discovery rate (r=0.16, P<0.03). In contrast, conception frequency (and, presumably, population sexual HPV transmission) was maximal near the vernal equinox, with relatively modest (<10%) seasonal fluctuation, i.e., not fully explaining this prominent August peak in HPV discovery. Conlusions There is a clear relationship between the detection of HPV-positive cervical smears and sunlight exposure. We speculate that the well-known phenomenon of UV-mediated suppression of immune surveillance may be causally related to this unusual increase in cytologically defined active HPV infections during the summer months in northern countries such as Holland. Confirming this relationship elsewhere may be important, because whatever the risk conferred by sunlight is, in principle, behaviorally avoidable.     

Cost effectiveness of biofeedback and behavioral medicine treatments: A review of the literature

This paper reviews multicomponent behavioral medicine studies that contain cost-effectiveness andor cost-benefit data relevant to the field of biofeedback and relaxation training, primarily when assisted by biofeedback, with or without stress management, in the treatment of psychosomatic illness and pain. A model for evaluating biofeedback treatment is presented. Cost-effectiveness data concerning reduction in physician visits and/or medication use, decrease in medical care costs to patients, reduction in hospital stays and rehospitalization, reduction of mortality, and enhanced quality of life are reviewed. Evidence suggests that multicomponent behavioral medicine treatments are cost-effective on all dimensions reviewed. Cost/benefit ratios range between 1:2 and 1:5, with a median of 1:4. Evidence that could increase the cost effectiveness of biofeedback is reviewed.This work first appeared in a paper presented as the presidential address at the 18th annual meeting of the Biofeedback Society of America, Boston, March 15, 1987.     

Beta-catenin accelerates human papilloma virus type-16 mediated cervical carcinogenesis in transgenic mice

Human papilloma virus (HPV) is the principal etiological agent of cervical cancer in women, and its DNA is present in virtually all of these tumors. However, exposure to the high-risk HPV types alone is insufficient for tumor development. Identifying specific collaborating factors that will lead to cervical cancer remains an unanswered question, especially because millions of women are exposed to HPV. Our earlier work using an in vitro model indicated that activation of the canonical Wnt pathway in HPV-positive epithelial cells was sufficient to induce anchorage independent growth. We therefore hypothesized that constitutive activation of this pathway might function as the "second hit." To address this possibility, we developed two double-transgenic (DT) mouse models, K14-E7/ΔN87βcat and K14-HPV16/ΔN87βcat that express either the proteins encoded by the E7 oncogene or the HPV16 early region along with constitutively active β-catenin, which was expressed by linking it to the keratin-14 (K14) promoter. We initiated tumor formation by treating all groups with estrogen for six months. Invasive cervical cancer was observed in 11% of the K14-ΔN87βcat mice, expressing activated β-catenin and in 50% of the animals expressing the HPV16 E7 oncogene. In double-transgenic mice, coexpression of β-catenin and HPV16 E7 induced invasive cervical cancer at about 7 months in 94% of the cases. We did not observe cervical cancer in any group unless the mice were treated with estrogen. In the second model, K14-HPV16 mice suffered cervical dysplasias, but this phenotype was not augmented in HPV16/ΔN87βcat mice. In summary, the phenotypes of the K14-E7/ΔN87βcat mice support the hypothesis that activation of the Wnt/β-catenin pathway in HPV-associated premalignant lesions plays a functional role in accelerating cervical carcinogenesis.     

The association of obesity and cervical cancer screening: a systematic review and meta-analysis

Obese women are at an increased risk of death from cervical cancer, but the explanation for this is unknown. Through our systematic review, we sought to determine whether obesity is associated with cervical cancer screening and whether this association differs by race. We identified original articles evaluating the relationship between body weight and Papanicolaou (Pap) testing in the United States through electronic (PubMed, CINAHL, and the Cochrane Library) and manual searching. We excluded studies in special populations or those not written in English. Two reviewers sequentially extracted study data and independently extracted quality using standardized forms. A total of 4,132 citations yielded 11 relevant studies. Ten studies suggested an inverse association between obesity and cervical cancer screening. Compared to women with a normal BMI, the combined odds ratios (95% CI) for Pap testing were 0.91 (0.80-1.03), 0.81 (0.70-0.93), 0.75 (0.64-0.88), and 0.62 (0.55-0.69) for the overweight and class I, class II, and class III obesity categories, respectively. Three out of four studies that presented the results by race found this held true for white women, but no study found this for black women. In conclusion, obese women are less likely to report being screened for cervical cancer than their lean counterparts, and this does not hold true for black women. Less screening may partly explain the higher cervical cancer mortality seen in obese white women.     

Human papilloma virus type 16 infection and the early onset of cervical cancer

Human papilloma viruses (HPV), particularly type 16, have been associated with cervical cancer. It has been noted that the average onset of cervical cancer is occurring in younger women coupled with a higher prevalence of cervical HPV infection. However, the correlation between HPV 16 infection and the early onset of cervical cancer is still unclear. We hypothesize that HPV infection is an indicator of early onset of cervical cancer. To test this hypothesis, cervical smears from 197 women were evaluated by the polymerase chain reaction for HPV 16. These data revealed that the HPV 16-positive women were significantly younger than the HPV 16-negative women. Moreover, the average age of HPV 16-positive women with CIN 3 or invasive cancer was significantly younger compared with the other groups. These data clearly suggest that HPV 16 infection is a significant risk factor for the progression for cervical cancer in a young population of women.     

Virus-associated human tumors: cervical carcinomas and papilloma viruses

The latest experimental data on the role of viruses in the origin of human tumors are discussed. This group of viruses consists of T-cell leukemia virus type 1 (HTLV 1), herpes viruses (HHV 8 and Epstein-Barr virus), hepatitis B virus, and human papilloma viruses. The most typical feature of this group of viruses is a very long latent period from the initial infection to the development of the disease that varies between 10 and 40 years. The mechanism of malignant cell conversion is specific for each viral type but is mainly associated with a disruption of functions of cellular genes participating in the control of cell division and proliferation. It can be a direct inactivation of tumor suppressor genes by their interaction with viral gene products (papilloma viruses), or a trans-activation of cellular genes modulating cell proliferation by viral gene products (hepatitis B virus and HTLV 1). Viruses play an initiative role and additional genetic changes in the genome of infected cells are necessary for complete expression of the oncogenic potential of the viral genes. Only these cells will give rise to a monoclonal cell population with uncontrolled proliferation. New approaches for the creation of vaccines against cancers associated with hepatitis B virus and papilloma viruses (hepatocellular carcinomas and cervical tumors, respectively) are in progress. These vaccines have been found to be effective in prevention of the disease in the experimental models and are now beginning to be used for human vaccination.     

Ensuring quality in cervical screening programmes based on molecular human papillomavirus testing

The increased use of human papillomavirus testing within cervical screening programmes necessarily brings about changes to the laboratory services required to support them. A crucial element of such services is to demonstrate initial and ongoing quality of the test (and associated processes). In this review, we outline some of the quality considerations and challenges with an emphasis on the laboratory including assay and platform validation, internal quality control selection and strengths and weaknesses of external quality assurance schemes. The influence and role of key external entities, including regulatory agencies, guideline groups, programme commissioners and commercial providers, are also discussed.