Acceptability and Preferences of Dry HR HPV Self-Sampling Mailed Kits Among Canadian Women: A Cross-Sectional Study

Human papillomavirus (HPV), a sexually transmitted disease, is identified as the source of 99.7% of cervical cancers. Screening for cervical cancer using oncogenic HPV (high-risk [HR] HPV) detection is more sensitive than traditional cytology. However, few Canadian data exist on HR HPV self-sampling.ObjectiveTo evaluate the acceptability of HR HPV self-sampling by patients, the percentage of correctly collected samples, the return rate of mailed kits, and the HPV positivity rate in a population sample based on different cervical cancer risk factors.MethodsWe conducted an observational cross-sectional study on HPV primary cervical cancer screening with self-collected cervicovaginal samples through mail service.ResultsA total of 400 kits were mailed and 310 kits were returned, making a return rate of 77.5%. Of these, 84.2% of patients were very satisfied with this method and 95.8% (297/310) of patients would choose self-sampling over cytology as their primary screening method. All patients would recommend this screening method to their friends or family members. Of the samples, 93.8% could be analyzed correctly and the HPV positivity rate was 11.7%.ConclusionIn this large and random sample, there was a strong interest in self-testing. Offering HR HPV self-sampling could increase access to cervical cancer screening. The self-screening method could also be a part of the solution to reaching under-screened populations, in particular, those who do not have a family doctor or avoid gynaecologic exams because of pain or anxiety.     

贵州省三都水族自取样HPV检测宫颈癌筛查及分流模式#br#

Objective?To explore a cervical cancer screening strategy suitable for remote minority areas in China. Methods?A total of 1 874 cases of shui minority women aged 21~65 years in Sandu were randomly sampled self-sampling HPV test, TCT test and P16 cytological immunohistochemical test. The patients with HPV positive, TCT abnormality (ASC-US) and P16+underwent colposcopy and biopsy, and squamous intraepithelial lesion (SIL) was detected. Results?The positive rate of HR-HPV was 15.69% in 1 874 women. HPV52 was the most common type, followed by HPV16, HPV39, HPV58 and HPV56. Among 249 patients with colposcopy biopsy, 23 cases (9.24%) were detected with HSIL or above lesions.The positive rates of p16 in HSIL and above cervical lesions, LSIL and cervicitis were 73.91%, 34.57% and 10.34% (P<0.001).The sensitivity of self-sampled HPV test to HSIL+ was 100%, and the area under ROC curve for HSIL+ detected by HPV-positive test and p16 test was 0.577 (P>0.05) and 0.774 (P<0.05), respectively. Conclusion?Self-sampled HPV was highly sensitive to HSIL. Using self-sampling HPV detection as primary screening, combined with p16 staining triage, can be used as a screening strategy in remote areas of Guizhou province to improve the coverage of screening.     

Integrating HPV testing for primary screening?

Cervical cancer, the second most common cancer in young women in France, is still today imperfectly screened even with the advent of primary prevention for this cancer in the form of prophylactic HPV vaccination. Indeed, the cervical Pap smear and its cytologic analysis, both operator and reader dependent, have limited sensitivities requiring repeated samplings and above all, producing a high rate of falsely negative tests. Although most cancers occur in women who are either not or insufficiently screened, the problem with cervical smears is the fact that cancers are also often diagnosed in young women having follow-ups in accordance with professional guidelines. The absence of an organized screening in France results in an inadequate female population coverage. Nowadays, it is unanimously recognized that high-risk papillomaviruses (HR HPV) represent the only independent risk factor for cervical cancer and that there cannot be any disease without this virus. It is therefore this strong association between a viral agent and the cervical cancer which opened the door firstly, to the notion of prophylactic vaccination and secondly, to the integration of HR HPV testing in the screening for precancerous lesions. Molecular biological techniques based on the HR HPV genome detection within the female genital tract have shown a very high sensitivity without any inter and intraobserver variability and an excellent negative predictive value. Their integration in the primary screening for cervical cancer would improve the relevance of the latter and would suit the need for a wider population coverage and even for an organized screening thanks to the possibility for self-sampling. The specificity of these tests is inferior to that of the cervical smear, but the management of the falsely positive HPV tests has proved to be efficient by sorting residual cells obtained from liquid-based cytology. What is urgent in France is the need for an organized screening programme in order to improve population coverage and, this does not go against neither a vaccination promotion nor the integration of new technologies. Moreover, the last three randomized trials published in October 2007 have shown that it was quite safely possible to extend the time interval between two consecutive viral testing and thus improving the cost-effectiveness of cervical cancer screening. The aim of this work was to analyze publications on the subject in order to conclude, according to proof levels obtained by different studies, on its usefulness in the secondary prevention of cervical cancer.     

Self-Collected Samples for Testing of Oncogenic Human Papillomavirus: A Systematic Review

BackgroundTo investigate the role of self-sampling for human papillomavirus (HPV) testing as an alternative to cervical cancer screening by clinicians (i.e., Papanicolaou [Pap] test).MethodsA systematic search of MEDLINE, EMBASE, Cochrane Library, and other sources for evidence related to the efficacy and feasibility of HPV DNA self-collection.ResultsA total of 25 studies were identified. In 22 comparisons across 19 studies, the concordance between samples collected by patients and those obtained by clinicians was reasonably high in the majority of cases. Women in many countries across wide age ranges were successful in collecting samples for HPV DNA testing. In four studies, the quality of the cytology from patient samples was as good as clinician samples, with more than 95% of samples yielding HPV DNA results. The studies that examined acceptability found that women were generally very positive about collecting their own samples, although some concerns were noted. No study evaluated the effect of HPV DNA self-sampling on screening participation rates, early detection, survival, or quality of life.ConclusionsSelf-sampling for HPV DNA testing is a viable screening option, but there is insufficient evidence to conclude that self-sampling for HPV DNA testing is an alternative to the Pap test. Although HPV DNA testing using self-collected samples holds promise for use in under-resourced areas or for women who are reluctant to participate in Pap testing programs, the evidence supporting it is limited. Further definitive research is needed to provide a solid evidence base to inform the use of self-sampling for HPV DNA testing for the purpose of increasing screening rates, especially in women who are never or seldom screened.     

Attitudes to self-sampling of vaginal smear for human papilloma virus analysis among women not attending organized cytological screening

BACKGROUND: The major problem with the cytological screening is the non-optimal participation rate among women invited for cervical smear collection. The aim of the present investigation was to examine the attitudes of the non-responding women to perform self-sampling of vaginal smear at home as a method to increase the coverage of the screening and to examine the prevalence of high-risk human papilloma virus (HPV) among the responding women. METHODS: From the database of the Department of Cytology, University Hospital of Uppsala 198 women, aged 35-55 years, who had not attended the organized gynaecological screening for over 6 years were identified. They were sent a letter of information about the study and one week later a self-sampling device aimed to collect vaginal smear. The vaginal smear of the women responding to the offer of self-sampling was analysed for high-risk HPV using Hybrid Capture 2 method or polymerase chain reaction amplification of HPV DNA. All women in the study also received a questionnaire in order to investigate their attitudes towards self-sampling as an alternative in the organized screening. RESULTS: Of the 198 women 15 women had to be excluded. Fifty-eight per cent of the women responded and collected vaginal smear at home and among them 7% were positive for high-risk HPV. The questionnaire revealed no significant difference of age, country of birth and occupation or marital status, on using self-sampling of vaginal smear at home. The attitudes among responding and non-responding women differed. The responding women who contributed by sampling vaginal smear were more positive to self-sampling of vaginal smear (p<0.01). CONCLUSIONS: Offering self-sampling of vaginal smear in women not attending the organized cytological screening increases the coverage and identifies an additional group of women with an increased risk to develop cervical cancer. The attitude towards self-sampling was mainly positive.     

高危型人乳头瘤病毒阳性患者宫颈病变风险预测方法及进展

宫颈癌的主要致病机制与高危型人乳头瘤病毒（HR-HPV）的持续性感染密切相关。HR-HPV检测已成为宫颈病变筛查的一个主要手段，其敏感度高、特异度差。因此，对持续性HR-HPV阳性患者的病变风险评估及分流判读尤为重要。随着对宫颈病变机制研究的深入，许多新兴分流手段逐步应用于临床：HR-HPV载量检测可以除外一些一过性感染患者；P16/Ki67细胞学双染使细胞学检查更为客观；HPV DNA甲基化、宿主DNA甲基化和微小RNA（miRNA）宫颈癌筛查不仅敏感度、特异度相对较高，同时使患者自采样成为可能；免疫微环境可以反映宫颈病变程度及免疫状态。这些新型检查手段在提供HR-HPV患者阴道镜分流的同时，对于宫颈病变风险预测均有很好的临床应用价值。现综述HPV阳性后除细胞学检测外新的检测分流手段，为临床HPV阳性后的进一步检查及风险预测提供参考。     

Human papillomavirus detection in self-collected vaginal specimens and matched clinician-collected cervical specimens

Human papillomavirus (HPV) detection is an integral part of cervical cancer screening, and a range of specimen collection procedures are being tested. Preliminary studies have found that the majority of women prefer self-collection of vaginal specimens instead of clinician-collected specimens of the cervix. The purposes of the current study were to explore the social and behavioral predictors of acceptance of self-collection of vaginal specimens among patients and to assess concordance in detection of HPV between clinician-collected cervical specimens and self-collected vaginal specimens. The study was conducted at a university family medicine clinic using a cross-sectional study design, and enrollment of women presenting for routine gynecological examination consecutively in a period of 1 year, self-administered questionnaires, collection of paired vaginal and cervical specimens for HPV DNA using Hybrid Capture 2, and cytologic analysis. Most women (79.8% [398/499]) agreed to collect vaginal specimens. In our study, 76.6% (216/282) African American women (AA), 88.1% (156/176) white non-Hispanic (WNH) women, and 63.4% (26/41) women of other races (P < 0.0001) agreed to self-collect vaginal specimens. HPV was detected in 16.0% (80/499) of clinician-collected cervical specimens and 26.1% (104/398) of self-collected vaginal specimens (P < 0.001). HPV detection was concordant in 13.4% (53/398) women in both cervical and vaginal specimens. Self-collection of vaginal specimens for HPV DNA detection is acceptable to most women presenting for routine gynecological examination. WNH women were more likely to obtain self-collected specimens than AA women. Vaginal specimens were more likely to be positive for HPV than were cervical specimens.     

Human papillomavirus testing and screening

Cervical cancer is a largely preventable disease through the detection, treatment and follow-up of its precursors. Traditionally, this has been accomplished through screening women with cervical cytology, and referring women with abnormal cytology for colposcopy, histological sampling and treatment. In organized programmes that achieve wide coverage of the target population at frequent intervals, this approach has resulted in a considerable reduction in cervical cancer. Recently, however, the development of reliable and reproducible tests for the detection of human papillomavirus (HPV) infection of the cervix (which is now accepted to be causally associated with the development of almost all cervical cancers) has led to the evaluation of HPV de-oxyribonucleic acid (DNA) testing as either an alternative or adjunctive test to cytology for the detection of cervical cancer and its precursors. There is now a large body of data supporting the clinical utility of HPV DNA testing for the prevention of cervical cancer, particularly in the settings of primary screening of women older than 30 years, in the triage of women with equivocal cytology and for the follow-up of women post-treatment.     

The use of human papillomavirus typing in detection of cervical neoplasia in Recife (Brazil)

Abstract. Lorenzato F, Ho L, Terry G, Singer A, Santos LC, de Lucena Batista R, Lubambo T. The use of human papillomavirus in detection of cervical neoplasia in Recife (Brazil).
High risk types of human papillomavirus (HR-HPV) play a major role in cervical cancer oncogenesis. This study aims to evaluate the efficacy of HPV detection and typing as a means of identifying cervical neoplasia in a high risk population. A management algorithm for implementation of HPV detection in clinical practice is also proposed. A nested case-control within a cohort study was undertaken in Recife (Brazil). All 479 participants had cervical scrapes collected for HPV detection followed by colposcopy. Samples were blindly analyzed by polymerase chain reaction (PCR) and typed by restriction fragment length polymorphism (RFLP).
HPV detection by PCR and typing with RFLP cost US$ 4.92 per woman screened in this study and is significantly better than cytology in identifying women at risk of developing cervical cancer ( P = 0.0001). Women who tested positive for HR-HPV had over 35-fold increased risk of having high grade squamous intraepithelial lesion (HSIL) or cervical cancer, although this does not necessarily translate into the same risk rate for women with latent HPV infection developing major cervical neoplasia. HPV typing offers 90% sensitivity and 85% specificity for cervical cancer detection. In combination with cytology it provides a negative predictive value of 99.4% and a sensitivity of over 96% for detection of HSIL and cervical cancer.
We conclude that HPV typing is an inexpensive and effective method for identification of cervical neoplasia and women at risk of developing it. It improves quality control for both false negative and false positive cytology results. Routine screening intervals could safely be increased to 3–5 years, decreasing anxiety and socio-economic inconveniences.     

Self-collecting a cervico-vaginal specimen for cervical cancer screening: An exploratory study of acceptability among medically underserved women in rural Appalachia

ObjectiveInnovative screening methods such as self-testing for human papillomavirus (HPV) may alleviate barriers to cervical cancer screening. The purpose of this exploratory study was to determine whether Appalachian Kentucky women would be amenable to self-collecting a cervico-vaginal specimen for HPV testing.MethodsWomen aged 30–64 who were overdue for guideline-recommended cervical cancer screening were recruited from a primary care clinic in southeastern Kentucky. The women were asked to self-collect a specimen, using a cervico-vaginal brush, based on verbal and printed directions provided by a research nurse. All study participants, regardless of laboratory-confirmed HPV status, received the same counseling on the importance of cervical cancer screening and offered navigation to follow-up Pap testing at the local health department.ResultsThirty-one women were approached and recruited to participate in the study, indicating a 100% acceptance rate of HPV self-testing. Of the 31 women, 26 tested negative for high-risk HPV and five tested positive. All of the women with negative results declined nurse navigation to Pap testing, whereas four of the five women with positive results accepted nurse navigation and received subsequent Pap smear screenings (all results were normal).ConclusionsAmong this sample of Appalachian Kentucky women, self-collecting a cervico-vaginal specimen for HPV testing was highly acceptable. This exploratory study provides impetus for larger studies among high-risk, medically underserved women in rural communities. Tailoring alternative cancer screening strategies to meet the complex needs of rural women is likely to lead to reductions in cervical cancer incidence and mortality among this vulnerable population.     

Interest of Human Papillomavirus DNA quantification and genotyping in paired cervical and urine samples to detect cervical lesions

Background

Cervical cancer is caused by persistent infection with high-risk human papillomavirus (HR-HPV). Conventional human papillomavirus (HPV) testing requires cervical sampling. However, vaginal and urine self-sampling methods are more acceptable for patients and result in increased participation when they are available in screening programs. In this context, we have developed a non-invasive screening method via the detection of HPV DNA in urine samples.

Purpose

To compare HPV viral loads and genotypes in paired cervical and urine samples, and to assess correlation between virological and cytological results in women seeking gynecological consultation.

Methods

Paired urine and cervical specimens were collected and analyzed from 230 of 245 women participating in the previously described prospective PapU study. HPV DNA detection and quantification were performed using a real-time PCR method with short fragment PCR primers. Genotyping was carried out using the INNO-LiPA HPV genotyping assay.

Results

The prevalence of HPV in the 230 paired urine and cervical smear samples was 42 and 49 %, respectively. Overall agreement for HPV positivity and negativity between the paired samples was 90 % (κ = 0.80). High HPV viral load in both cervical and urine samples was associated with cytological abnormalities. HPV-positive women were mostly infected with HR-HPV types. The agreement between high- and low-risk HPV (LR-HPV) detection in both samples was 97 % (κ = 0.95 for HR-HPV and κ = 0.97 for LR-HPV).

Conclusions

High concordance rates for HPV-DNA quantification and high/low-risk HPV genotyping in paired urine/cervical samples suggest that urinary HPV DNA testing could be useful for cervical lesion screening.     

The role of human papillomavirus in risk management

In the UK, systematic cervical screening with high population coverage has been successful in reducing both the incidence and mortality from cervical cancer but further improvements are limited by the inherent performance of the Papanicalaou smear test. Early cross-sectional data on association between HPV infection and cervical intraepithelial neoplasia (CIN) has generated world-wide interest in HPV testing to enhance both the sensitivity and specificity of cervical screening. Whilst infection with HPV is recognised as the single most important factor in the development of cervical disease, for most women these infections are transient and of no clinical significance. Very few infections ultimately result in invasive cancer, which is associated with oncogenic subtypes and HPV DNA persistence. Data from large prospective longitudinal clinical studies on the efficiency and cost-effectiveness of HPV testing are just beginning to be reported and HPV testing cannot be recommended in routine clinical care as yet. However, the available evidence on the natural history of HPV infection and the development of CIN does highlight clinical situations in which HPV may have an important role in assessing risk. These are women with low-grade smear results, women on surveillance after the treatment of CIN and older women who could be exited early from the national screening programme. The key function may be to identify those women at such low risk that they no longer warrant intensive surveillance or indeed to continue screening.     

新一代杂交捕获技术在宫颈癌筛查中的应用

目的:了解新一代杂交捕获技术(DH2)在宫颈癌筛查与传统筛查方式的优势比较,探讨HPV16/18分型检测对DH2初筛阳性患者分流管理的临床意义。方法:2013年、2014年、2015年分别对浙江省慈溪市79847例、81702例、61072例妇女采用巴氏涂片的方法进行宫颈癌筛查,在2015年、2016年分别对浙江省慈溪市35657例、59634例妇女使用DH2检测14种高危型HPV的方法进行宫颈癌筛查。以病理诊断作为金标准,分析高危型HPV检测与巴氏涂片在LSIL以上病变的检出率情况。同时对DH2阳性患者进行HPV16/18检测,对照和比较HPV16/18分流策略的检出情况。结果:2013年、2014年、2015年采用巴氏涂片的方法对LSIL以上病变的检出率分别为0.048%、0.105%、0.134%;2015年、2016年使用DH2检测14种高危型HPV的方法对LSIL以上病变的检出率分别为0.415%、0.550%。2015年采用DH2检测14种高危型HPV初筛模式,LSIL以上病变在DH2阳性及在HPV16/18阳性中的占比分别为4.644%、15.370%;2016年采用DH2检测14种高危型HPV初筛及初筛阳性患者HPV16/18分流的模式,LSIL以上病变在DH2阳性及在HPV16/18阳性中的占比分别为6.365%、22.430%。结论:使用DH2检测14种高危型HPV的方法比传统巴氏涂片对LSIL以上病变的检出率更高,DH2可作为宫颈癌初筛的可行方法;DH2初筛及初筛阳性患者HPV16/18分流管理模式对宫颈癌高危人群进行风险分层管理,重点关注HPV16/18阳性人群,可以进一步提高宫颈癌筛查中的LSIL以上病变检出率。     

TCT联合高危型HPV基因检测在绝经后妇女宫颈上皮内瘤变筛查的价值评估

目的:评价宫颈薄层液基细胞检测(TCT)联合高危型HPV基因分型检测在绝经后妇女宫颈上皮内瘤变(CIN)筛查的价值。方法:选取TCT检查结果异常,包括意义不明不典型鳞状细胞(ASCUS)、低度鳞状上皮内瘤变(LSIL)、高度鳞状上皮内瘤变(HSIL)和鳞状上皮癌(SCC)的163例绝经后妇女为研究对象,荧光定量PCR(FQ-PCR)法检测高危型人乳头状瘤病毒(HR-HPV16、18、31、33、45、52、56、58)分型,并以阴道镜下宫颈活检病理学诊断作为诊断金标准进行对比研究。结果:①不同年龄段绝经妇女TCT结果异常的类型构成比,差异无统计学意义(P>0.05)。②HPV分型检测阳性者80例,感染率49.1%,随着TCT检查宫颈病变级别的升高,HR-HPV感染率亦逐步增加,与低级别比,差异有统计学意义(P<0.05)。③163例TCT异常患者中,病理学诊断阳性51例(CINⅠ级24,CINⅡ级9例,CINⅢ级6例,宫颈浸润癌12例),阳性率31.3%(51/163)。随着TCT检查宫颈癌变级别的增高,宫颈组织病理学诊断阳性率逐步增加,差异有统计学意义(P<0.01)。④宫颈炎组中HR-HPV阳性40例,感染率35.71%,宫颈CIN阳性组中HR-HPV阳性29例,感染率74.4%(其中CIN I级70.8%,CIN II级77.8%,CIN III级83.3%),宫颈浸润癌组中HR-HPV阳性11例,感染率91.7%,随着宫颈病变病理级别的升高,HR-HPV感染率呈上升趋势(P<0.01)。⑤TCT联合HPV检测、单独HPV检测对CIN及宫颈癌筛查的敏感度均高于TCT检查,分别为96.1%、78.4%、66.7%(P<0.01)。TCT联合HPV分型检测、单独HPV检测对CIN及宫颈癌筛查的假阴性率低于TCT检测,有显著性统计学差异(P<0.01)。3种筛查方法的特异度、假阳性率比较,无统计学差异(P>0.05)。结论:TCT联合高危型HPV基因分型检测在绝经后妇女宫颈上皮内瘤变筛查中具有重要意义。     

Accuracy of dry vaginal self-sampling for detecting high-risk human papillomavirus infection in cervical cancer screening: A cross-sectional study

Objective

Cervical cancer screening coverage remains insufficient in most countries. Testing self-collected samples for high-risk human papillomavirus (HR-HPV) could be an alternative to the Pap smear, but costs, sampling methods and transport issues hamper its wide use. Our objective was to compare diagnostic accuracy of 2 vaginal self-collection methods, a dry swab (vsc-DRY) or swab in liquid medium (vsc-LIQ), for detecting HR-HPV cervical infection assessed by a cervical clinician-collected sample in liquid medium (ccc-LIQ).

Methods

Women 20 to 65 years attending a Pap smear were recruited between September, 2009 and March, 2011. Each sample (3 per woman) underwent HPV DNA testing. Samples were classified as HR-HPV + with detection of at least one HR-HPV or probable HR-HPV type.

Results

Of 734 women included, 722 had complete HPV data. HR-HPV was detected in 20.9% of ccc-LIQ samples. Estimated sensitivity and specificity to detect HR-HPV in vsc-DRY samples were 88.7% and 92.5%, respectively, and in vsc-LIQ samples, 87.4% and 90.9%. Cytology findings were abnormal for 79 women (10.9%): among 27 samples of low-grade squamous intraepithelial lesions, 25 were HR-HPV + in vsc-DRY, vsc-LIQ and ccc-LIQ samples. Among 6 samples of high-grade squamous intraepithelial lesions, all were HR-HPV + in vsc-DRY samples, 1 was HR-HPV − in vsc-LIQ samples and 1 was HR-HPV − in ccc-LIQ samples.

Conclusions

Vaginal self-sampling with a dry swab is accurate to detect HR-HPV infection as compared with cervical clinician-collection and accurate as compared with cytology results. This cheap and easy-to-ship sampling method could be widely used in a cervical cancer screening program.     

Randomized clinical trial of PCR-determined human papillomavirus detection methods: self-sampling versus clinician-directed--biologic concordance and women's preferences

OBJECTIVE: The purpose of this study was to compare the high-risk human papillomavirus detection rates from self-sampled swabs and tampons with standard clinician-directed speculum sampling and to assess women's acceptance of self-sampling methods. STUDY DESIGN: One hundred three women who required a colposcopy underwent order randomization of the human papillomavirus sampling technique. Kappa and McNemar test statistical results were used to measure the agreement between clinician-directed and self-sampling techniques for high-risk types of human papillomavirus and the acceptance of self-sampling techniques. RESULTS: All self-directed samplings were equivalent to clinician sampling for all cervical intraepithelial neoplasia disease states. High-risk human papillomavirus was detected by self- and clinician-directed methods in 83% of the women with cervical intraepithelial neoplasia, grade 2/3. The 2 sequential swabs trend toward better detection of high-risk types of human papillomavirus than all other techniques for women with normal histologic factors (P =.0736, by McNemar's chi2 test). Ninety-four percent of women would accept self-sampling for their yearly cervical screen. CONCLUSION: Self-sampling is equivalent to clinician sampling for the detection of high-risk human papillomavirus and is acceptable to women as a yearly screen.     

Detection of HPV infection by analyzing the changes in structure of peripheral blood lymphocytes specifically induced by HPV E7 antigen

PURPOSE: Detection of human papilloma virus (HPV) infection in clinical practice was examined based on the observation that peripheral blood lymphocytes exposed in vitro to antigenic or mitogenic stimulation change their intracellular structures as measured by polarization of fluorescent light emitted by labeled cells. MATERIALS AND METHODS: A total of 47 women were enrolled in this study. They were classified into four groups based on the results of HPV-DNA detection in cervical tissues by the Hybrid Capture II kit (Digene, Gaithersburg, MD, USA) and pathological examination. Ten women with no HPV-DNA detection were used as a normal control group. Fifteen women without pathological diagnosis in the cervical tissues had HPV-DNA detection. Ten women with CIN lesions had 80% HPV-DNA detection. Twelve women with invasive squamous cell carcinoma had 100% HPV detection. Peripheral blood lymphocytes derived from all women were collected and then exposed to HPV-E7 antigen and PHA mitogen. RESULTS: The positive response rate of HPV-E7 antigen was ten percent (1/10) in the normal control group, 73.3% (11/15) in the HPV infectious women, 50% (5/10) in the CIN women, and 91.7% (11/12) in the cervical cancer patients. The overall sensitivity rate of blood tests was 77.1% and the specificity rate was 57.8% when the Hybrid Capture II HPV Test kit was used as the standard detection method for cervical tissue. CONCLUSIONS: The results showed that peripheral blood lymphocytes derived from patients with cervical lesions might be another choice to be used as a screening method to detect HPV infection compared with conventional methods.     

p16/Ki-67双染在宫颈癌及癌前病变初筛中的应用价值研究

目的:评价采用p16/Ki-67双染检测技术作为宫颈癌及癌前病变初筛方法的效果及应用价值。方法:对重庆市万州区982例年龄35~64岁有性生活的妇女进行宫颈癌筛查。每位妇女均接受了人乳头瘤病毒DNA(HPV DNA)检测、Thin Prep液基细胞学检查、p16/Ki-67双染检测,对结果异常者进行阴道镜检查,阴道镜下在可见病变处直接取活检,无可见病变时,行宫颈管搔刮术(ECC)。比较3种方法分别作为初筛手段识别宫颈癌前病变(高级别鳞状上皮内病变)及浸润癌的灵敏度、特异度、阳性预测值和阴性预测值等指标,以受试者工作特征(ROC)曲线下面积(AUC)综合分析3种方法作为宫颈癌初筛手段的应用价值。结果:最终966例妇女进入研究,共检出高级别鳞状上皮内病变及浸润癌患者42例。HPV DNA检测、液基细胞学检查和p16/Ki-67检测对宫颈癌及癌前病变患者的灵敏度分别为97.6%、88.1%、92.9%;特异度分别为84.1%、78.8%、82.8%;阳性预测值分别为21.8%、15.9%、19.7%;阴性预测值分别为99.9%、99.3%、99.6%。p16/Ki-67检测的AUC分别与HPV DNA检测、液基细胞学检查相比,差异均无统计学意义(P0.05)。结论:p16/Ki-67双染检测初筛宫颈癌及癌前病变的效果与HPV DNA检测及液基细胞学检查相似,因其具有简便、客观、高效、易于重复的特点,p16/Ki-67双染检测为宫颈癌及癌前病变的有效初筛提供了一种新选择。     

The current status of HPV DNA testing

Infection with high-risk types of HPV underlies most cases of high-grade cervical intraepithelial neoplasia (CIN) and practically all cases of invasive cervical cancer. Currently, cervical HPV DNA is detected by means of PCR and sandwich capture molecular hybridization methods. Research has focused on the potential role of HPV testing in three conditions: screening for cervical neoplasia, triage of women with low-grade lesions and follow-up after conservative surgical treatment for CIN. Concerning the first condition, HPV testing does not seem to offer an obvious advantage over traditional cytology screening, mainly due to false positive results in younger women with transient HPV infection. A possible exemption to this is the case of middle-aged women and low-resource settings, where the excellent sensitivity of a HPV test is desirable. Although data are controversial regarding low grade lesions, results from randomized studies indicate that HPV testing could be useful in a triage of women with an initial cytological diagnosis of ASCUS, where detection of DNA of a high-risk type should lead to colposcopy. Although there is a lack of randomized controlled trials in this field, data from observational studies indicate that HPV DNA testing after conservative surgical treatment for CIN may be very sensitive and detect early residual and recurrent disease.