Clinical validation of high risk HPV DNA testing versus ThinPrep cytology for primary cervical cancer screening

Objective(s)To compare the validity of the high risk HPV DNA testing using the hybrid capture II technique (HC-II) to ThinPrep cytology for primary cervical cancer screening.DesignCross sectional pilot study.SettingDepartment of Obstetrics and Gynecology, Taiba Hospital, Sabah Al Salem, Kuwait.MethodsConsecutive 1923 cervical smear samples were taken for ThinPrep cytological screening and hr-HPV DNA testing using HC-II assay. Histological diagnoses were obtained from a total of 426 women who had positive results on screening and a group of women with negative screening and suspicious cervix underwent colposcopy and directed biopsies, and those with cervical precancerous lesions or cancer received appropriate treatment.Main outcome measuresSensitivity, specificity, positive predictive value and negative predictive value of screening methods.ResultsHPV was found positive in 15.5% of cases. 19/22 cases (86.4.1%) with a biopsy diagnosis of CIN2+ had a HC-II positive test. For CIN3, HC-II was positive in all cases (100%). Assuming a similar specificity level, the relative sensitivity of the HC-II test was higher when histologically confirmed high grade lesions (CIN2+ or CIN3+) were observed. HC-II test had the best sensitivity when defining cases as CIN2+ or CIN3+ (98.7% and 100%, respectively). When using the ASCUS+ cytological cutoff, the differences in CIN2+ and CIN3+ sensitivity between HC-II test and ThinPrep cytology were statistically not significant. Specificity of the ThinPrep cytology for any low and high grade histological lesions was clearly >95% when cytological diagnosis LSIL+ cutoff was used and nearly 100% when HSIL+ cutoff was used. All these specificity estimates were high compared with HC-II test. The specificity of the ThinPrep cytology decreased with about 10% when ASCUS+ was the cutoff. At cutoff ASCUS+, specificity of HC-II was comparable or only slightly lower than with ThinPrep ASCUS+ cytology with no statistically significant differences.ConclusionsThinPrep smears and hr-HPV DNA detection by HC-II performed very well with regard to identifying high grade lesions. HPV DNA testing is a promising new technology for cervical cancer prevention and can be used for primary screening in conjunction with cervical cytology for women aged 30 years and older.     

The evaluation of human papillomavirus DNA testing in primary screening for cervical lesions in a large Japanese population

To examine the utility of human papillomavirus (HPV) DNA testing for the screening of cervical cancer and its precursors, a prospective cohort study was performed in which a total of 8156 women with a median age of 36 years were enrolled. Two smear samples scraped from the uterine cervix were served for Papanicolaou test and HPV DNA testing (Hybrid Capture-II system). HPV-positive samples were further examined for HPV subtype using a DNA microarray chip. Women with cytologic abnormality or those with high-risk HPV DNA were further examined by colposcopy to determine histologic diagnosis. High-risk HPV DNA was detected in 11% of the general population, with higher prevalence of specific types, including 52, 16, 58, 51, 56, and 18. As expected, younger women were likely to have increased frequency of HPV infection. Notably, HPV DNA testing detected all 45 cases of cervical intraepithelial neoplasia (CIN) 3, while cytologic findings were negative in 6 of these cases. It is of particular interest that CIN was commonly associated with multiple HPV types, while invasive cancers had a single type of HPV. In terms of both sensitivity and positive predictive value in detecting the CIN, HPV DNA testing is superior to cytology. However, most importantly, HPV DNA testing in combination with cytology significantly improved the efficacy to CIN screening.     

Human papillomavirus (HPV) genotyping by HPV DNA chip in cervical cancer and precancerous lesions

OBJECTIVES: The human papillomavirus (HPV) is a well-known cause of cervical cancer. HPV tests are used as an adjunct test to decrease the false-negative rate of cytological screening. However, attempts are being made to replace the cytological screening with HPV tests. Therefore, this study was performed to examine the possibility of using HPV tests as screening test. MATERIALS AND METHODS: The results of the tests that were performed at the same time including the ThinPrep cytology, the high-risk group hybrid capture II (HC-II) test, the HPV DNA chip (HD-C) test, and a punch biopsy were compared in 400 women who were referred to us due to abnormal cytology or cervicogram. The accuracy of each test was then evaluated, and the type of virus was investigated using a HD-C test. RESULTS: The positive predictive values detected by the high-risk group HC-II test and HD-C test according to the histological diagnosis outcomes were 56.8 and 53.8%, respectively, for cervicitis; 91.5 and 91.5%, respectively, for cervical intraepithelial neoplasia I (CIN I); 88.1% and 81.0%, respectively, for CIN II; 88.6 and 84.2%, respectively, for CIN III, and 92.5 and 88.7%, respectively, for cancer (in 53 patients). The most prevalent types of HPV according to the HPV tests were types 16, 58, 18, and 52 in which type 16 was detected in the more advanced lesions. The sensitivity was 88.4% for the ThinPrep cytology, 89.9% for the HC-II for the high-risk group, and 86.2% for the HD-C test. CONCLUSION: These results suggest the possibility of using the HC-II and HD-C tests as screening tests, which have a similar sensitivity as the ThinPrep cytology. Nonetheless, randomized controlled trials will be needed before the actual application of the HPV tests as screening tests. Despite the fact that the importance of HPV type 16 in cancer development was confirmed, the prevalence of types 58 and 52 were relatively high compared with those found in other studies, showing a need for further studies on this subject. These HPV types need to be considered in vaccine development.     

Adoption of HPV testing as an adjunct to conventional cytology in cervical cancer screening in Japan

Objective

To assess the effectiveness of including HPV testing as an adjunct to conventional cytology in cervical cancer screening.

Methods

Atypical epithelial cells (ATC) were classified according to the 2001 Bethesda classification system. The study ran for 6 years from May 2004 to November 2009 in conjunction with public cervical cancer screening for Kanazawa City residents. Patients with ATC (ASC-US, ASC-H, and AGC) underwent parallel testing for high-risk HPV types with the Hybrid Capture II system; HPV positive and cytology-ATC cases were recalled for colposcopic examination and biopsied if necessary. Results were compared with those obtained before HPV screening was initiated.

Results

A total of 62 645 women underwent screening over the 6-year period; of these, 3622 (5.8%) were ATC positive, among whom 527 (14.5%) tested HPV-positive. These 527 women (0.8% of the screened population) were recalled for colposcopic examination. The resulting 426 biopsies were diagnosed as CIN 1 (n = 187), CIN 2 (n = 53), CIN 3 (n = 11), and invasive cervical cancer (n = 2).

Conclusion

HPV testing as an adjunct to conventional cytology in cervical cancer screening seems to increase detection sensitivity with proven cost-effectiveness.     

宫颈癌筛查系统及液基细胞学检测在宫颈病变筛查中的对比研究

目的:探讨宫颈癌筛查系统(TruScreen)与液基细胞学检测(liquid-based cytologytest,LCT)在宫颈病变诊断中的临床意义。方法:对487例患者行TruScreen、LCT检查,以阴道镜下病理学检查为金标准。比较两种方法的敏感度、特异度及假阴性率。结果:TruScreen、LCT阳性结果分别为229例和42例,病理学检查阳性结果为30例。Tru-Screen、LCT及TruScreen联合LCT检测的敏感度分别为73.3%、46.7%和90%,特异度分别为54.7%、93.9%和50.5%,假阴性率分别为26.7%、53.3%和10%。TruScreen及Tr-uScreen联合LCT检查敏感度高于LCT,差异有统计学意义(P<0.05),TruScreen与Tru-Screen联合LCT检查的敏感度无统计学差异(P>0.05)。结论:本研究中,TruScreen的效果评价高于LCT。在我国,TruScreen作为一种新的宫颈病变筛查技术可能会达到较好的筛查效果。     

Urine-based human papillomavirus DNA testing as a screening tool for cervical cancer in high-risk women

Objective

To test the hypothesis that self-collected urine could be used to detect high-risk human papillomavirus (HPV) DNA with sensitivity and specificity comparable to those of standard cervical testing.

Methods

Women attending a gynecology clinic for evaluation of abnormal cytology were recruited. Fifty-two participants (21–60 years of age) collected urine samples, and clinicians collected cervical brush samples. When appropriate, cervical biopsies were obtained during colposcopy. HPV detection and typing were performed on DNA extracts from each sample, using commercial reagents for L1 consensus polymerase chain reaction (PCR) and type-specific hybridization. HPV 16 viral load was determined by quantitative PCR in HPV 16-positive samples. A diagnostic test analysis was conducted for urine samples.

Results

Fifty paired samples were analyzed, with 76% agreement between samples. The 12 discrepant pairs were all urine negative/cervix positive. The most common HPV types detected were 16, 51, 53, and 62. The urine test correctly identified 100% of the uninfected and 65% of the infected patients.

Conclusion

The results indicate that HPV DNA detection using urine is less sensitive than cervical sampling in a population with abnormal cytology. Further exploration is warranted to determine clinical utility when other options are unavailable.     

Human papillomavirus (HPV) DNA detection in self-collected urine

OBJECTIVE: Non-invasive sampling of human genitals to identify high-risk individuals with subclinical oncogenic HPV infection remains a challenge. The study was designed to see if self-collected urine can be used as a simple, non-invasive sampling for screening HPV, particularly for screening/monitoring general population or young adolescents or infants, if they are to be immunized by HPV vaccines. METHOD: Self-collected urine samples from 100 sexually unexposed college going girls and cervical scrapes from 104 normal healthy sexually active married women were used in this study. Additionally, a group of 55 women were recruited for collecting first urine and later scraped cervical cells to validate urine sampling by directly comparing HPV positivity between the two types of biological specimens. A dry 'paper smear' method for specimen collection and a simple single tube protocol was employed for PCR detection of HPV infection. RESULTS: Out of 100 sexually inexperienced college going girls, only 6 (6%) were positive for HPV infection as revealed by L1 consensus primer and 4 (4%) of them were positive for HPV 16 but none was found positive for HPV 18 DNA. Out of 104 sexually active married women who were cytologically reported as negative by Pap test, 11 (10.5%) were found HPV positive and 7 (6.7%) of them had infection of high-risk HPV type 16. Both urine and later cervical scrapes from a group of 55 women collected as dry 'paper smear' showed perfect matching positivity for HPV between urine and cervical scrape. CONCLUSIONS: The use of urine coupled with its dry collection as 'paper smear' facilitating their easy transport, storage and direct PCR detection of HPV DNA opens up an alternative non-invasive approach for population screening of HPV infection, at least in such cases as children and infants in whom invasive samples are difficult to obtain.     

Human papillomavirus testing for primary screening in women at low risk of developing cervical cancer. The Greek experience

OBJECTIVE: To compare the performance of human papillomavirus (HPV) DNA detection against routine Papanicolaou smear for the detection of low- and high-grade cervical intraepithelial neoplasia in a low-risk population. MATERIALS AND METHODS: A cross-sectional study was performed involving 1296 women attending six outpatient clinics in Northern Greece (Thessaloniki, Thermi, Mihaniona, Corfu, Veria, and Serres). Women underwent a gynecological examination, including collection of exfoliated cervical cells for Papanicolaou cytology and HPV DNA detection. Cytology was processed according the conventional routine manner, and HPV DNA was determined using the polymerase chain reaction technique. In positive cases of either method, a complete colposcopic evaluation was performed with directed biopsies. Tests (HPV DNA, cytology, and colposcopy) performance characteristics were determined using the histopathologic diagnosis as the reference standard. RESULTS: HPV DNA testing showed a significantly better sensitivity than the Papanicolaou smear in detecting cervical intraepithelial neoplasia (75% versus 50% for high-grade lesions and 81.2% versus 50% for lesions of any grade, respectively). Specificity, and positive and negative predictive values did not significantly differ. Even after dividing women in younger or older than 30 years, the sensitivity of the HPV DNA test was greater than cytology (100% and 70% versus 50% for cytology in both groups, respectively), with a 6.3% loss in specificity when performed in women younger than 30 years. CONCLUSION: HPV testing could be useful in screening women at low risk for cervical cancer, either as an adjunct tool to augment existing cytology programs or as a unique test of its own.     

高危型HPV DNA检测在宫颈上皮内瘤变及宫颈早期鳞癌锥切术后随访中的应用及意义

目的:探讨高危型HPV(HR-HPV)DNA检测在宫颈上皮内瘤变(CIN)及宫颈鳞癌(ⅠA1期)患者经宫颈冷刀锥切术治疗后随访中的应用及意义。方法:2008年1月至2010年10月我院收治的308例CINⅡ～Ⅲ及宫颈鳞癌(ⅠA1期)患者经宫颈冷刀锥切术治疗后,采用第二代杂交捕获试验(HC2)检测HR-HPV DNA联合液基细胞学随访,观察术后HR-HPV清除及宫颈病变复发情况,并分析术后HR-HPV持续感染及病变持续或复发的相关因素。结果:至随访结束,宫颈锥切术后病变持续或复发者共10例。术后病变持续或复发在HR-HPV持续感染组中明显多于HR-HPV转阴组(P<0.001);术前HR-HPV DNA高负荷、病变累及3～4个象限为术后HR-HPV持续感染的高危因素;术前HR-HPV DNA≥500RIUs/CO是术后病变持续或复发的独立危险因素。结论:HR-HPV持续感染是宫颈锥切术后病变持续或复发的重要因素,术前HR-HPV DNA高负荷是术后HR-HPV持续感染及病变持续或复发的独立危险因素,术后应重点随访。     

内蒙古少数民族地区宫颈癌的筛查方法研究

目的探讨内蒙古少数民族聚居区宫颈癌及癌前病变适宜的筛查方法。方法2009年4月-8月对内蒙古自治区鄂尔多斯、兴安盟、通辽三个地区的2958名年龄30～59岁的已婚妇女进行了宫颈癌筛查。取宫颈脱落细胞,做人乳头瘤病毒（HPV-HC2）检测;同时用醋酸着色及碘着色（VIA/VILI）肉眼观察的方法进行筛查。对HPV-HC2阳性或VIA/VILI肉眼观察异常或两者均异常者,行阴道镜检查,在可疑处取宫颈组织活检,必要时行颈管诊刮术（ECC）;送组织病理学检查确诊。结果内蒙古鄂尔多斯、通辽、兴安盟三地区HPV总感染率为17.36%,中度及以上宫颈上皮内瘤样病变（≥CIN2）和宫颈癌的检出率为0.9%;应用HPV-HC2筛出阳性者最后确诊≥CIN2者27例,而用VIA/VILI仅确诊13例,漏诊14例。结论HPV检测结合醋酸、碘肉眼观察是宫颈癌筛查的有效方法。在内蒙等经济发展不均衡地区,可尝试采用HPV检测进行初筛,对HPV阳性患者用VIA＋VILI或者细胞学筛查的方法进行分流的筛查策略,降低漏诊率,也相对降低HPV阳性患者阴道镜的转诊率。