Telomerase assay and HPV 16/18 typing as adjunct to conventional cytological cervical cancer screening.

OBJECTIVE: This study aims at exploring the potential use of telomerase activity assay and typing of human papillomaviruses (HPV) 16 and 18 in improving the identification of high-grade cervical intraepithelial neoplasia (CIN). METHODS: From 86 women with normal cervical smears and from 114 patients with abnormal cervical smears cervical scrapings were collected. The telomerase activity was assayed using the Telomerase Repeat Amplification Protocol, and HPV was detected using consensus primers and specific primers for HPV 16 and HPV 18. RESULTS: HPV 16 in cervical scrapes was significantly associated with high-grade squamous epithelial lesions on cytology and with high-grade CIN, i.e., CIN 2/3 on biopsy. The detection of HPV 18 or telomerase activity had no significant association with high-grade squamous intraepithelial lesions or high-grade CIN. CONCLUSION: The use of the telomerase activity assay in cervical scrapes, unlike HPV 16 typing, did not improve the detection of high-grade CIN.     

Human papillomavirus detection by hybrid capture II and residual or recurrent high-grade squamous cervical intraepithelial neoplasia after large loop excision of the transformation zone (LLETZ)

AIMS AND BACKGROUND: The purpose of this study was to assess the association between highly-oncogenic types HPV DNA detection by Hybrid Capture II (HCII) and residual or recurrent high-grade cervical intraepithelial neoplasia (CIN 2 or 3) during the follow-up of women submitted to large loop excision of the transformation zone (LLETZ). STUDY DESIGN: In this cohort study, 94 women submitted to LLETZ because of CIN 2 or 3 between March 2001 and September 2002 were followed up twice yearly until September 2003. Follow-up visits consisted of an interview regarding clinical, social and demographic characteristics complemented with gynecological examination with specimen collection for Pap test and HCII and colposcopy. Eighty-one patients attended the first visit (mean 4.8 months, range 3-6) and 75 the second visit (mean 10.9 months, range 7-17 months). McNemar's test to assess the variation of HPV DNA detection following LLETZ, odds ratios (OR) to evaluate the correlation between HPV DNA positivity and residual/recurrent CIN during follow-up, and logistic regression to assess the risk of residual/recurrent CIN were used. RESULTS: There was a strong and significant reduction in HPV detection after LLETZ (P < 0.001). HPV DNA detection was correlated with residual/recurrent CIN at the first (OR = 103.4; 95% CI 5.5 to 1961.2) and second (OR = 12.7; 95% CI 1.1 to 345.5) follow-up visits. Multivariate analysis showed HPV persistence as a stand-alone risk factor for residual/recurrent CIN (OR = 50.3; 95% CI 3.8 to 663.1). CONCLUSIONS: High risk HPV DNA detection decreased substantially after CIN treatment with LLETZ, but HPV persistence was strongly correlated with residual/recurrent CIN.     

Pap Smear Combined with HPV Testing: A Reasonable Tool for Women with High-grade Cervical Intraepithelial Neoplasia Treated by LEEP

Background: To evaluate HPV testing by Hybrid Capture II (HCII) in conjunction with cytology in detectingthe residual/recurrence disease after treatment of high-grade cervical intraepithelial neoplasia (CIN II-III) withloop electrosurgical excision procedure (LEEP). Materials and Methods: A retrospective review of 158 patientswith histologically confirmed CIN II-III who underwent LEEP between January 2011 and October 2012 wasconducted. Post-treatment control was scheduled at the 3rd, 6th, 12th and 18th month. All patients were followedup by Pap smear and HR-HPV genotype and viral load testing. Results: Pre-treatment, HR-HPV DNA, wasdetected in all specimens of the patients. At follow-up, 25 patients were diagnosed as the residual/recurrent diseaseduring the FU visit, among whom, 16 patients with positive margin: 13 patients (52%) with HR-HPV DNA+/cytology+, 2 patients (8%) with HR-HPV DNA+/cytology-, 1 patient (4%) with cytology+/ HR-HPV DNA-; 9patients with clean margin – 5 patients (55.6%) with HR-HPV DNA+/cytology+; 2 patients (22.2%) with HRHPVDNA+/cytology-, 2 patients (22.2%) with cytology+/ HR-HPV DNA-. None of them persisting HR-HPVDNA-/cytology- with positive or negative margin was identified as the residual/recurrent disease. The majorityof residual/recurrent disease was detected at the 12th and 18th month FU, and there was almost no differencein the sensitivity and negative predictive value (NPV) between at the 3rd month and the 6th month FU visits. 14residual/recurrence disease (14/46:30.4%) had pre-treatment high viral load (>5 000 RUL/PC) and 11 (11/112,9.8%) with pre-treatment low viral load, P<0.05. Conclusions: (1) The persistence HR-HPV DNA is the rootcause of the residual/recurrent disease for the women treated for high-grade CIN; the pre-treatment viral loadand margin can be seen as the predictor. (2) The FU visit beginning at the 6th month post-treatment and lastingat least 24 months with the combination of cytology and HPV testing. (3) Patients with high pre-treatment HPVload, which is considered as one risk of developing the residual/recurrent disease, should be paid more attention(especially above 500RUL/PC) to by clinicians.     

LCT联合HR-HPV检测在宫颈上皮内瘤变Ⅲ级LLETZ术后随访中的价值

  目的  评价HR-HPV(high-risk human papillomavirus)检测在CINⅢ(cervical intraepithelial neoplasia gradeⅢ)行宫颈移行区大环切除术(LLETZ)后随访中的价值。  方法  采用临床病例分析的方法, 选取北京大学深圳医院2003年5月至2009年5月间诊断为CINⅢ接受LLETZ(large loop excision of the transformation zone)手术的567例患者, 术后3、6个月及以后每6~12个月随访1次, 以LCT(liquid-based cytologic test)及HCⅡ(hybrid captured-Ⅱ)法HR-HPV DNA检测作为随访的监测指标, 评估LCT联合HR-HPV检测在术后随访中的价值。  结果  1) 术后LCT预测病变残留灵敏度60.00%, 特异度88.15%, 阳性预测值8.30%, 阴性预测值99.19%;HPV预测病变残留灵敏度100%, 特异度85.64%, 阳性预测值11.11%, 阴性预测值100%;LCT预测病变复发灵敏度63.64%, 特异度92.27%, 阳性预测值14.00%, 阴性预测值99.23%;HPV预测病变复发灵敏度72.73%, 特异度85.97%, 阳性预测值9.30%, 阴性预测值99.38%。2)术后HPV持续阳性患者复发几率高于非HPV持续感染患者, 差异有统计学意义(P < 0.05)。术后复发率在HPV持续阳性组与再次感染组为高, HPV持续阴性组术后无复发。  结论  术后LCT联合HR-HPV检测预测残留或复发有重要价值, 是一种有效的随诊方法。术后HPV感染状态与复发相关, 临床需严密随访。      

Persistence and load of high-risk HPV are predictors for development of high-grade cervical lesions: a longitudinal French cohort study

Oncogenic HPV types are the major cause of worldwide cervical cancer, but only a small proportion of infected women will develop high-grade cervical intraepithelial neoplasia or cancer (CIN2/3+). We performed a prospective study including 781 women with normal, atypical squamous cells of undetermined significance (ASCUS) or low-grade squamous intraepithelial lesion (LGSIL) cytology, and infected or not by high-risk (HR) HPV tested by Hybrid Capture II. Women were followed up every 6 months for a median period of 22 months. Among the HR-HPV-positive women at entry, more than half cleared their virus in 7.5 months; the clearance rate was greater for low viral loads than for high loads and also was higher in women with an initial ASCUS/LGSIL smear than in women with normal cytology. The incidence of cytologic abnormalities strongly depended on baseline viral load and HR-HPV persistence. Maintenance of cytologic abnormalities was associated with the outcome of HR-HPV status (negative or =100 pg/mL). Conversely, women who were consistently HR-HPV negative or transiently HR-HPV positive, whatever the cytology at baseline was, did not develop CIN2/3+ during follow-up. Age seemed to affect only the rate of incident HR-HPV infection. In conclusion, our data suggest that women repeatedly tested positive for HR-HPV are at risk of developing CIN2/3+, even when initial cytology is normal. A high viral load could be used as a short-term marker of progression toward precancerous lesions, although lower load does not inevitably exclude progressive disease.     

PAX1 Methylation Analysis by MS-HRM is Useful in Triage of High-grade Squamous Intraepithelial Lesions

This study is aimed to investigate the role of paired boxed gene 1 (PAX1) methylation analysis by methylationsensitivehigh-resolution melting (MS-HRM) in the detection of high grade lesions in atypical squamous cellscannot exclude high-grade squamous intraepithelial lesion (ASC-H) and compared its performance with theHybrid Capture 2 (HC2) human papillomavirus (HPV) test. In our study, 130 cases with a diagnosis of ASC-Hfrom the cervical cytological screening by Thinprep cytologic test (TCT) technique were selected for triage.Their cervical scrapings were collected and evaluated by using PAX1 methylation analysis (MS-HRM) andhigh-risk HPV DNA test (HC2), followed by colposcopy and cervical biopsy. Chi-square test were used to testthe differences of PAX1 methylation or HPV infection between groups. In the detection of CIN2+, the sensitivity,specificity, the PPV, NPV and the accuracy of PAX1 MS-HRM assay and high-risk HPV (HR-HPV) tests wererespectively 80.6% vs 67.7%, 94.9% vs 54.5%, 83.3%, vs 31.8%, 94.0% vs 84.4%, and 91.5% vs 57.7%. ThePAX1 MS-HRM assay proved superior to HR-HPV testing in the detection of high grade lesions (CIN2+) inASC-H. This approach could screen out the majority of high grade lesion cases of ASC-H, and thus could reducethe referral rate to colposcopy.     

Inclusion of HPV testing in routine cervical cancer screening for women above 29 years in Germany: results for 8466 patients

In a prospective cohort study 8466 women attending routine cervical cancer screening were recruited. Colposcopy was performed on women with any degree of atypia on cytology and/or a positive high-risk human papillomavirus (HPV)-DNA test (HC2; Hybrid Capture 2((c))), and for a randomly selected sample of 3.4% women with negative findings on both. Quality control included reviews of cytology, histology, colposcopy images and retesting of samples with polymerase chain reaction. Test diagnostic performances were based on 7908 women who had complete baseline and follow-up results. Routine histology identified 86 women with high-grade cervical intraepithelial neoplasia (CIN2+), which was confirmed by review histology in only 46 cases. Sensitivity of routine cytology for the detection of CIN2+ was 43.5%, with a specificity, positive predictive value (PPV), negative predictive value (NPV) of 98.0, 11.4 and 99.7%, respectively. Sensitivity of the HC2 test for the detection of CIN2+ was 97.8%, with a specificity, PPV and NPV, of 95.3, 10.9 and 100%, respectively. No high-grade neoplasia was detected in the randomly selected control group. A negative HPV-test result, even in combination with a positive Papanicolaou (Pap) result, virtually excluded any risk of underlying high-grade disease, but this was not the case for a negative Pap result. These data show that HPV testing is of value for the detection or exclusion of prevalent CIN in a routine cervical cancer-screening setting and could be used for further risk classification of women for follow-up management.     

Comparative analysis of human papillomavirus detection by hybrid capture assay and routine cytologic screening to detect high-grade cervical lesions

A commercial HPV detection test, Hybrid Capture (HC), designed to detect 14 HPV types divided into high-risk and low-risk groups, has been evaluated. A total of 1064 scrapes from 1028 unselected women attending routine cytologic screening were tested and results were compared with those of classic cytologic screening and cervical biopsies. The reliability of the test was also evaluated on 38 fresh conization samples. HPV DNA was detected in 108 women (10.5%), including 90 infected by a high-risk HPV (8.8%); 25 high-grade lesions were detected histologically, and high-risk HPV was found in 16 of these 25 women (64%), and in 27 (71%) of the 38 conization samples. The overall sensitivity of HC in detecting high-grade SIL on cervical scrapes and conization samples was 71.2%, while its positive predictive value was 17.8%. Classic cytologic screening appeared to be the most sensitive method (84%) for detecting high-grade SIL, with a positive predictive value of 91.3%. The lower sensitivity of HC limits its use for screening high-grade lesions on a large scale, even though it may be useful for reducing cytologically false-negative results. Moreover, the quantitative approach provided by the HC assay for assessment of the viral load cannot clearly distinguish among cases with or without high-grade lesions. Int. J. Cancer 75:525–528, 1998.© 1998 Wiley-Liss, Inc.     

轻度宫颈上皮内瘤变自然转归的前瞻性研究

[目的]研究轻度宫颈上皮内瘤变（CINⅠ）的自然转归、人乳头瘤病毒（HPV）的自然清除率及两者之间的关系。[方法]对2003年5月到2006年4月期间,在北京大学深圳医院经阴道镜下活检病理诊断为CINⅠ的548名患者,定期随访4～6年。以宫颈液基细胞学检查（LCT）联合高危型HPV（HR-HPV）DNA检测（HC-Ⅱ）作为随访的监测方法,每6～12月随访一次。对于随访中细胞学为未明确诊断意义的不典型鳞状上皮细胞（ASCUS）及以上病变,及/或HR-HPV阳性者行阴道镜下多点活检,病理诊断。[结果]随访48个月时共失访27人,剔除34人,继续随访487人,累积未完全随访率为11.13%。随访6个月、12个月、24个月、36个月、48个月时进展为高度宫颈上皮内瘤变的百分率分别为0.55%、1.65%、3.10%、4.05%、4.11%;病变持续存在的百分率分别为70.25%、45.77%、23.79%、11.54%、7.19%;病变逆转为正常的百分率分别为29.20%、52.57%、73.11%、84.41%、88.71%。随访48个月时,35岁以上组和35岁以下组的病变进展率和逆转率均无显著性差异。随访开始时HR-HPV阳性的患者462例,随访6个月、12个月、24个月、36个月、48个月时病毒自然清除率分别为24.26%、48.69%、70.05%、81.54%、86.36%,HPV清除与CINⅠ病变逆转趋势一致。24个月内HPV持续阳性的患者,在48个月内进展为高度宫颈上皮内瘤变的比率为18.9%,显著高于HPV阴转组和HPV持续阴性组。[结论]2年内超过2/3的CINⅠ病变会自然逆转,HPV也会自然清除,但对于HPV持续阳性的患者应警惕其进展为高度宫颈上皮内瘤变。     

高危型人乳头瘤病毒对宫颈病变治疗后监测临床意义研究

目的 人乳头瘤病毒(human papillomavirus,HPV)在宫颈癌发生、发展过程中具有重要作用,为此本研究通过动态观察HPV的变化,探讨高危型人乳头瘤病毒(high-risk human papillomavirus,HR-HPV)在宫颈上皮内瘤变(cervical intraepithelial neoplasia,CIN)及Ⅰ期宫颈癌治疗后临床监测中的意义.方法 选择2010-01-01-2012-12-31新疆医科大学附属肿瘤医院收治的327例CIN(CIN Ⅰ 52例,CINⅡ40例,CINⅢ142例)及Ⅰ期宫颈癌(93例)患者为研究对象,分析其临床资料并动态检测HR-HPV,观察其治疗前后HR-HPV感染率、转阴率和持续感染率以及病变的复发率.结果 宫颈病变的HR-HPV总感染率为89.9％,CIN及Ⅰ期宫颈癌各组感染情况比较,CINⅡ与CINⅢ级之间差异有统计学意义、但存在样本量相差较大问题,其余各组比较差异均无统计学意义.CIN及Ⅰ期宫颈癌手术治疗后HR-HPV总转阴率为78.9％,各组宫颈病变的HR-HPV转阴率差异无统计学意义,P＞0.05;但HR-HPV转阴的平均时间为5～6个月,治疗后6个月是CIN Ⅰ与CINⅢ的HR-HPV转阴高峰期,治疗后9个月是CINⅡ及宫颈癌Ⅰ期HR-HPV转阴高峰期.年龄≤35岁(A组)、35～45岁(B组)、46～55岁(C组)和≥56岁(D组)间HR-HPV转阴时间,总体差异有统计学意义,P＜0.05.进一步行组间两两比较结果显示,A组与C组、A组与D组、B组与C组、B组与D组间差异有统计学意义,P＜0.05;A组与B组、C组与D组间差异无统计学意义,P＞0.05.本组随访时间为6.5～60.0个月,中位随访时间为28.3个月.CIN组HR-HPV持续感染者9例,均复发,平均复发时间16.3个月;HR-HPV阳性持续存在率和复发率明显高于术后HR-HPV转阴患者,差异有统计学意义(P＜0.05),灵敏度100％,特异度100％.宫颈癌Ⅰ期患者术后随访HR-HPV持续感染者9例,均复发,另有1例HR-HPV检测阴性者复发,平均复发时间16.8个月;HR-HPV阳性持续存在率和复发率明显高于术后HPV转阴患者,差异有统计学意义(P＜0.05),灵敏度90％,特异度100％.结论 HR-HPV的动态变化可作为CIN、宫颈癌治疗后随访监测的良好指标,持续HR-HPV感染高度预警宫颈病变的复发,具有一定的临床意义.     

女性下生殖道HPV感染与宫颈上皮内瘤变及宫颈癌关系的病理研究

目的：探讨女性下生殖道高危型人乳头状瘤病毒（high risk human papillomavirus,HR－HPV）感染与宫颈上皮内瘤变（cervical intraepithelial neoplasia,CIN）及宫颈癌的关系。方法：选择2013年2月－2015年4月我院收治的236例CIN及宫颈癌患者为观察组,进行下生殖道HPV（人乳头状瘤病毒）检测,分析CIN及宫颈癌与HPV感染的关系,并与对照组有宫颈炎但无CIN及宫颈癌的126例患者进行对比研究。结果：HR－HPV感染率随着患者CIN 的严重程度而升高,宫颈癌的HR－HPV感染率最高为91．89％,明显高于对照组差异具有统计学意义（P＜0．05）。HR－HPV双重感染率以及HR－HPV多重感染率与单一HR－HPV患者的病毒感染率相比较高,差异具有统计学意义（P＜0．05）。且患者随着病情的加重,单型、双重、多重HR－HPV感染率从CINⅠ期、CINⅡ期、CINⅢ期呈递增趋势。结论：HR－HPV感染及HR－HPV多重感染是导致宫颈上皮内瘤变及宫颈癌发生的重要诱因,对高危型 HPV 病毒的持续感染,及时的诊断并予以有效的治疗,能够阻滞癌前病变的发展,对于预防宫颈上皮内瘤变及宫颈癌,降低宫颈癌的死亡率具有重要临床意义。     

Value of HPV (hybrid capture 2) testing for assessing the effectiveness of conservative surgical treatment in CIN2-3/carcinoma in situ and microinvasive cervical cancer

The prospective study in 525 patients with CIN2-3/CIS and microinvasive cervical cancer showed the association of epithelial lesions with HPV HR in almost all cases. This allowed using HPV-testing for conservative surgical treatment (ablation, LEEP/ LLETZ, conization) efficacy assessment and patient follow-up. The value of HPV-testing for residual disease and recurrence detection was higher that of cytology and colposcopy. HPV-testing showed 100% sensitivity and negative predictive value. Hybrid Capture 2 test was more useful for residual disease and recurrence detection than PCR, showed higher specificity (96% vs. 79,2%) and positive predictive value (44.8% vs. 13.4%). After conservative surgical treatment of CIN2-3/carcinoma in situ and microinvasive cervical cancer Hybride Capture 2 is to become negative thus confirming the adequacy of neoplastic tissue excision.     

Triage using HPV-testing in persistent borderline and mildly dyskaryotic smears: proposal for new guidelines

In the Netherlands 2% of cervical smears in the cervical cancer screening program are read as borderline or mildly dyskaryotic cytology (BMD smear). Only in about 10% of these women a high-grade CIN lesion (CIN II-III) is present; therefore referral is for the majority unnecessary. In our study triage with high-risk HPV (hrHPV) testing was used to identify women at risk for development of high-grade CIN lesions after a repeat BMD smear. A "wait-and-see" period was incorporated allowing clearance of HPV and regression of the lesion. Women with a low-grade lesion, irrespective of their HPV status, were monitored at 12 months; women with a high-grade lesion were monitored at 6 and 12 months. Fifty-one of the 105 women (49%) were hrHPV negative at baseline; none of them showed progression of the lesion within the first year of follow-up (NPV 100%). High-grade CIN was present in 1 patient who was HPV negative at baseline (2%); she demonstrated regression after 12 months. Nineteen of the hrHPV positive women (35%) demonstrated a high-grade CIN lesion at baseline and 3 cleared hrHPV after 6 months, with a subsequent regression of CIN. Ten women remained hrHPV positive with persistence of high-grade CIN and were eventually treated. At baseline, 35 hrHPV positive women demonstrated a low-grade lesion, 19 remained hrHPV positive after 12 months and 5 developed high-grade CIN. Sixteen out of the 35 cleared the hrHPV infection without progression of the lesion. In conclusion, triage, using hrHPV testing for women with persistent BMD cytology, can select women who are not at risk for development of high-grade CIN. We recommend return to the screening program without referral for colposcopic examination if hrHPV is absent. For hrHPV positive women, a repeat hrHPV test after another 6 months is suggested. Referral is only required if persistence of hrHPV is established.     

Human papillomavirus 16 load in normal and abnormal cervical scrapes: an indicator of CIN II/III and viral clearance

The relation between human papillomavirus type 16 (HPV 16) viral load in cervical scrapes and development of high-grade cervical intraepithelial neoplasia (CIN II or III) was studied in a nested case-control study of women with normal cytology (group A) and in a cohort of women with abnormal cytology (group B). HPV 16 DNA load was determined using a quantitative real-time PCR assay. In group A, case women (women with CIN II/III, n = 12) had a significantly higher viral load than control women (women with CIN < or = I, n = 47). This resulted in an increased relative risk of women with the 50% highest viral load for development of CIN II/III (OR 7.7; CI 1.6-33). In group B, women with CIN II/III (n = 38) had a significantly higher viral load than women with CIN < or = I (n = 25). Women with the 50% highest viral load had an increased relative risk of CIN II/III (OR 3.2; CI 1.1-9.3) and a decreased chance of both viral clearance and cytologic regression. Our data suggest that in women with normal cytology an increased HPV 16 load confers an increased risk of developing a CIN lesion. A sustained high viral load is subsequently informative for progression to a high-grade CIN lesion.     

Usefulness of liquid-based cytology specimens for the immunocytochemical study of p16 expression and human papillomavirus testing: a comparative study using simultaneously sampled histology materials

BACKGROUND: In cervical lesions, the overexpression of p16 is reported to be closely associated with high-risk human papillomavirus (HPV) infection. The objective of the current study was to confirm the usefulness of liquid-based cervical specimens for p16 staining as well as tissue sections. METHODS: A total of 98 patients with cervical lesions were entered into the current study. After the cytologic examination using liquid-based cervical smears, the same slides were immunostained for p16 and were compared with slides of simultaneously obtained, immunohistologically stained tissue sections. Moreover, the status of the HPV infection was examined by polymerase chain reaction using residual cytologic samples. RESULTS: Using liquid-based Pap smears, 98 cases were diagnosed as atypical squamous cells of undetermined significance (38 cases), low-grade squamous intraepithelial lesion (12 cases), high-grade squamous intraepithelial lesion (HSIL) (33 cases), and invasive carcinoma (15 cases). The concordance rate between the cytologic and histologic diagnoses was found to be higher in high-grade lesions compared with low-grade lesions. Immunohistochemistry revealed that all HSIL and invasive carcinoma cases contained p16-positive cells in the liquid-based Pap smears and diffuse p16 staining was observed in all high-grade lesions with greater than CIN Grade 3 cervical intraepithelial neoplasia except for two adenocarcinoma cases. Of the 98 cases, 60 were found to be positive for high-risk HPV and 55 of these 60 HPV-positive cases were found to be p16 positive on cytologic examination. There were 16 cases that demonstrated marked discrepancies between the cytologic and histologic diagnoses. CONCLUSIONS: The results of the current study confirmed that the immunohistochemical detection of p16 was more sensitive and specific than HPV status in cervical lesions using a liquid-based method as well as tissue samples, suggesting that p16 should be used as a satisfactory biomarker for the primary screening of cervical cytology.     

Human papillomavirus testing in primary screening for the detection of high-grade cervical lesions: a study of 7932 women

High-risk human papillomaviruses (HR-HPV) are the necessary cause of cervical carcinomas. To determine whether HPR-HPV DNA detection in primary routine screening could represent a sensitive and reliable technique for the detection of high-grade squamous intraepithelial lesions (HGSIL), laboratory analysis using 2 cytologic techniques (conventional and liquid-based), HPV testing with Hybrid Capture II assay (HC-II), followed by colposcopic examination of women with abnormal cervical finding and/or persistent HR-HPV infection, was conducted in 7932 women who had routine cervical examination. The sensitivity of HPV testing for detecting a histologically proven HGSIL was 100%, higher than that of conventional (68.1%) and liquid-based (87.8%) cytology. The low specificities of 85.6% and 87.3% of HPV testing slightly increased to 88.4% and 90.1% if HPV testing was reserved for woman >30 years old. The quantitative approach provided by the HC-II assay for the assessment of the viral load was not reliable for predicting HGSIL in normal smears. HR-HPV testing could be proposed in primary screening in association with cytology. With conventional cytology it significantly improves the detection of HGSIL. With the use of the same cervical scrape for HPV testing and liquid-based cytology, HR-HPV testing would allow to select positive samples treated in a second time for cytology which gives a good specificity.     

Human papillomavirus 'reflex' testing as a screening method in cases of minor cytological abnormalities

The aim was to evaluate human papillomavirus (HPV) 'reflex genotyping' in cases of minor cytological abnormalities detected in the gynaecological screening programme in Stockholm, Sweden. Liquid-based cytology samples showing minor cytological abnormalities were analysed using HPV genotyping (Linear Array, Roche diagnostics). Colposcopically directed cervical biopsies were obtained and the HPV test results were correlated with the histological results. In all, 63% (70/112) of the samples were high-risk (HR) HPV (HR-HPV) positive. A statistically significant correlation was found between high-grade cervical lesions and HR-HPV (P=0.019), among which HPV 16, 18, and 31 were the most important. The negative predictive value of HR-HPV detection for histologically confirmed high-grade lesions was 100%. An age limit for HPV reflex testing may be motivated in cases of low-grade squamous intraepithelial neoplasia (LSIL), because of high HR-HPV prevalence among younger women. By using HPV reflex genotyping, additional extensive workup can safely be avoided in about 50% of all cases of atypical squamous cells of undetermined significance (ASCUS) and LSIL among women 30 years. This screening strategy could potentially reduce the total abnormal cytology-reporting rate in the Swedish screening programme by about 1% and provide more accurately directed follow-up, guided by cytological appearance and HPV test results.     

高危型人乳头瘤病毒检测对宫颈上皮内瘤样病变诊断价值的探讨

目的:探讨在ASC-H患者中检测HR-HPV DNA预测宫颈上皮内瘤样病变(CIN)和浸润癌的价值,为完善CIN和浸润癌的筛查方案提供依据.方法:研究宫颈薄层液基细胞学诊断为ASC-H的患者68例,均进行HR-HPV DNA检测并在阴道镜下行宫颈组织活检,综合评价HR-HPV预测高级别CIN的价值.结果:在ASC-H中CIN发生率为52.9％(36/68),CINⅡ及以上病变(CINⅡ、CINⅢ及浸润癌)发生率为33.8％(23/68); HR-HPV检测阳性率为70.6％(48/68),HR-HPV阳性组CINⅡ及以上病变发生率为47.9％(23/48),HR-HPV阴性组CINⅡ及以上病变发生率为0(0/20),两组比较差异有统计学意义,x2=14.797,P=0.001,HR-HPV诊断CINⅡ及以上病变的敏感度和特异度分别为100.0％和44.4％,阳性预测价值和阴性预测价值分别为47.9％和100.0％.结论:初步研究结果提示,HR-HPV阳性ASC-H患者应高度警惕CINⅡ及以上病变发生,建议立即行阴道镜检查;而HR-HPV阴性患者可不进行阴道镜检查.     

Negative human papillomavirus testing in normal smears selects a population at low risk for developing high-grade cervical lesions

High-risk human papillomaviruses (HR-HPV) are the necessary cause of cervical carcinomas and there is an increasing interest in using HR-HPV DNA detection in adjunction to cytological examination for primary cervical screening. To determine whether women with a normal smear negative for HR-HPV DNA detection with the Hybrid Capture II assay might represent a low-risk population for developing a high-grade squamous intraepithelial lesion (HSIL), 4401 women have been followed in a period of 12-72 months (median=34 months). During this follow-up, four HSIL and one microinvasive carcinoma have been detected in this cohort (three in the cohort of 3526 women >29 years). The global negative predictive value (NPV) of double-negative tests is thus of 99.9% (ninety-five percent confidence interval (95% CI): 99.8-100%), whereas cytology alone gives an NPV of 99.2% (95% CI: 98.9-99.5%). If we obtain a second negative HR-HPV test 1-2 years after the initial test, the NPV is 100%. The NPV is also of 100% in the cohort of women >49 years. We conclude that all these women could be safely screened at longer intervals between 3 and 5 years. This policy will offset the increased costs induced by an additional HR-HPV testing in primary screening.