High-risk HPV testing in women with borderline and mild dyskaryosis: long-term follow-up data and clinical relevance.

In The Netherlands and most other European countries, women with two serial cervical smears with borderline or mild dyskaryosis (BMD) within 6 months are referred for colposcopy-directed biopsies. Only about 10% of these women have high-grade cervical intraepithelial neoplasia (CIN). This study therefore investigated whether human papillomavirus (HPV) testing could identify which women with smears read as BMD are most likely to have high-grade CIN, either at referral or during follow-up and the relationship was determined between clearance of high-risk HPV and regression of abnormal cytology. Women with smears read as BMD (n=278) were referred to the gynaecologist for colposcopy. They were subdivided into two groups; group A comprised women with a single smear (n=172) and group B women with two sequential smears (n=106) read as BMD before referral. High-risk HPV detection with Hybrid Capture II (HC II) was performed on a cervical scrape taken at the first visit before colposcopy (i.e. baseline smear) and during follow-up. Biopsies were taken when lesions suspected for CIN were seen at colposcopy. High-risk HPV DNA was present in the baseline smears of 126 (45.0%) women; 26 (20.6%) of them had histologically confirmed CIN 2/3 at the first visit and another 14 (11.1%) during follow-up. Only one of the 152 women (0.7%) with a negative high-risk HPV test had a CIN 2 lesion at the first visit and no CIN lesions were detected during follow-up of these women. After exclusion of women who were treated for prevalent high-grade CIN, the median follow-up times were 1.3 years (range 0.0-4.3 years) and 1.6 years (range 0.0-4.5 years) for women with HPV-negative and HPV-positive baseline smears, respectively. The sensitivity of a positive high-risk HPV test for CIN 2/3 at the first visit was 96.3%, the specificity 60.2%, the positive predictive value 20.6%, and the negative predictive value 99.3%. These values did not change markedly when stratified for group A or group B. Thus, a high-risk HPV positive test was strongly associated with the presence at the first visit and the development of CIN 2/3 lesions during follow-up. Moreover, regression of abnormal cytology in women with a positive high-risk HPV test at baseline was strongly associated with viral clearance and occurred 0.3 years (range -1.2 to 1.7 years) later than HPV clearance. This study establishes the value of a high-risk HPV positive test for women at risk of high-grade CIN, with virtually no risk for missing CIN 2/3. Addition of a test on high-risk HPV in women with BMD could prevent 55% of the referrals and/or repeat smears.     

Validation of ThermoFisher's Papspin for human papillomavirus detection in cervicovaginal specimens using PCR with GP5+/GP6+ primers and the Hybrid Capture II assay

The present study aimed to validate ThermoFisher's (Thermo Fisher Scientific, Runcorn, Cheshire, UK) Papspin (PS) for human papillomavirus (HPV) testing by in-house PCR and by the Hybrid Capture II (HC2) assay and to compare the results with those obtained using Specimen Transport Medium (STM) (Digene Diagnostics, Gaithersburg, MD, USA). Forty-five patients underwent conization for known lesions ranging from atypical squamous cells of undetermined significance (ASC-US) with high-risk HPV (hr-HPV) to high-grade squamous intraepithelial lesion (H-SIL/CIN2+) or adenocarcinoma. Two negative controls were included: one patient with post-menopausal bleeding and another from whom an inflammatory cervical sample was taken without conization. Prior to conization, a gynaecologist collected two cervical samples, fixed in PS or STM, from each patient. All but four cases were tested for panHPV (GP5+/GP6+) and specific hr-HPV subtypes (HPV16, 18, 31,33) by PCR using both media and all were processed for HC2. This study demonstrates that both HPV detection techniques work with PS, showing a specificity of 78.3% for HC2 and 92.8% for PCR compared to 83.8% for HC2 and 92% for PCR using STM. The efficacy of detecting HPV in PS-preserved H-SIL/CIN2+ was very high (96% for PCR using PS and 86% for HC2 using PS), which was in the same range as for PCR using STM, and which was only slightly lower than for HC2 using STM (96% and 89%, respectively). The differences were not statistically significant. It is concluded that ThermoFisher's PS is a valid liquid-based cytology medium for cervical samples, convenient for HPV testing by PCR with GP5+/GP6+ primers and by the HC2 assay.     

Detection of persistent high risk human papillomavirus infections with hybrid capture II and SPF10/LiPA.

BACKGROUND: HPV infection in young women is common. However only a certain number of HPV genotypes are oncogenic. It is necessary for high risk HPV infection to persist at the cervix for a considerable time before oncogenesis occurs. OBJECTIVES: To look for persistence of high risk HPV in women attending a colposcopy clinic. Two DNA detection methods were used and the results compared to determine the rates of persistent, resolved and acquired infections over a 6-month period. HPV genotyping was used to determine type specific persistence. STUDY DESIGN: One hundred and thirty-eight women were tested for HPV infection when attending the colposcopy clinic at UCLH and then tested again at a subsequent visit approximately 6 months later. HPV DNA was detected by the Digene HC II assay using the high risk probes only and by PCR with the SPF10 primer set. All SPF10 PCR-positive samples were then specifically genotyped by a Line Probe Assay (LiPA) [Kleter et al. 1999. J. Clin. Microbiol. 1999;37:2508]. RESULTS: At entry of the study high risk HPV was detected in 43% of the samples by Digene HC II and in 60% of the samples by SPF10/LiPA. Thirty-eight (28%) of the women had a true persistent infection with the same high risk HPV genotype over a median period of 6.3 months. Nine (7%) women resolved one HR HPV infection after their first colposcopy visit, but obtained a different high risk HPV infection by the time they were tested at their second visit as identified by LiPA. Thirty-seven (27%) of the 138 women had mixed HPV infections, representing 45% of all those infected. CONCLUSIONS: The SPF10/LiPA assay detected more high risk infections than the Digene HC II assay. The Digene HC II assay was unable to distinguish between persistent infections with the same high risk genotype and those where the genotype had changed between visits.     

Factors affecting residual/recurrent cervical intraepithelial neoplasia after cervical conization with negative margins

To identify factors for predicting residual or recurrent cervical intraepithelial neoplasia (CIN) after cervical conization with negative margins. A total of 172 patients with histologically verified high‐grade squamous intraepithelial lesions who underwent conization with negative margins were recruited at the General Hospital of Tianjin Medical University from December 2006 to January 2016. Follow‐up comprised clinical examination, a liquid‐based cytology test, a human papillomavirus (HPV) DNA genotyping test, colposcopy assessment, and if indicated, colposcopy‐directed punch biopsy. The Kaplan‐Meier method was used to analyze the median recurrent time, whereas log‐rank tests and Cox regression models were used to determine the predictors of residual/recurrent CIN. Fourteen residual/recurrent cases (8.1%) were identified in 172 patients. In univariate analysis, cytologic abnormalities on follow‐up (P = .000), conization method (P = .017), HPV positivity at any visit (P = .000), persistent HPV infection postconization (P = .000), persistent infection with the same HPV genotype (P = .000), and HPV positivity at 18 months after conization (P = .000) were predictive factors of residual/recurrent CIN. The results of multivariate analysis further revealed that persistent HPV infection postconization (P = .035), HPV positivity at 18 months after conization (P = .017), and cytologic abnormalities on follow‐up (P = .000) had an increased risk of residual/recurrent CIN. During follow‐up, patients with persistent HPV infection or cytologic abnormalities were at high risk of residual/recurrent CIN and should be identified for close surveillance and monitoring. Meanwhile, patients with HPV who became negative within 18 months after treatment had a low risk of recurrence.     

Comparison between prototype hybrid capture 3 and hybrid capture 2 human papillomavirus DNA assays for detection of high-grade cervical intraepithelial neoplasia and cancer

We compared the performance of a prototype version of the Hybrid Capture 3 (HC3) human papillomavirus (HPV) DNA assay to the current generation Hybrid Capture 2 (HC2) assay, both of which target 13 oncogenic HPV types, for the detection of cervical intraepithelial neoplasia grade 3 and cancer (CIN3+) with cervicovaginal lavage specimens collected at enrollment into a 10-year cohort study at Kaiser Permanente (Portland, Oreg.). HC3 results for a risk-stratified sample (n = 4,364) were compared to HC2 results for the entire cohort (n = 20,810) with receiver operating characteristics curves, and the optimal cut points for both tests (relative light units [RLU]/positive control [PC]) for the detection of CIN3+ were determined. Specimens were also tested for HPV16 and HPV18 with separate HC3 type-specific probes. The optimal cut point for detecting CIN3+ was 1.0 RLU/PC for HC2, as previously shown, and was 0.6 RLU/PC for HC3. At the optimal cut points, HC3 and HC2 had similar screening performance characteristics for CIN3+ diagnosed at the enrollment visit. In analyses that included cases CIN3+ at enrollment and those diagnosed during early follow-up, HC3 had nonsignificantly higher sensitivity and equal specificity for the detection of CIN3+ compared to HC2; this increase in sensitivity was primarily the result of increased detection of CIN3+ in women who were 30 years of age or older and were cytologically negative (P = 0.006). We also compared the performance of the hybrid capture tests to MY09/11 L1 consensus primer PCR results (n = 1,247). HC3 was less likely than HC2 to test positive for specimens that tested positive by PCR for any untargeted types (P < 0.001). HC3 was less likely than HC2 to test positive for untargeted PCR-detected single infections with HPV53 (P = 0.001) and HPV66 (P = 0.01). There was good agreement between test positivity by PCR and by single type-specific HC3 probes for HPV16 (kappa = 0.76; 95% confidence interval [CI] = 0.71 to 0.82) and for HPV18 (kappa = 0.73; 95% CI = 0.68 to 0.79). In conclusion, we suggest that HC3 (>/=0.6 RLU/PC) may be slightly more sensitive than and equally specific test as HC2 (>/=1.0 RLU/PC) for the detection of CIN3+ over the duration of typical screening intervals.     

Equivocal and weakly positive hybrid capture 2 tests in women aged 50 and older

The performance of the Hybrid Capture 2 (HC2) test for human papilloma virus (HPV) detection depends on the prevalence of infection. However, the current HC2 manufacturer recommended interpretative algorithm is the same for all women. This test, which may be particularly useful in perimenopausal and postmenopausal women given the morphologic complexity of their Pap tests, could be affected by the overall lower prevalence of HPV infection in this age group. We investigated HC2 equivocal and weakly positive HPV tests in women 50 years and older and the detection of high-grade dysplasia (CIN2+) on their follow-up specimens. All HC2 test data from 1,067 consecutive specimens and 85 additional specimens from women ≥ 50-years-old with equivocal and weakly positive HC2 were analyzed. Follow-up specimens from women with HC2 tests within these ranges were reviewed. No CIN2+ was found on follow-up of 49 cases of women ≥ 50 with equivocal or weakly positive HC2 results. The current HC2 algorithm resulted in "positive" reports in 63% of specimens with initial equivocal HC2 due to retests mostly within the equivocal range. These results suggest that women 50 years and older may benefit from higher HC2 thresholds. The test could also be reported as HC2 values (RLU/CO) to be interpreted in view of risk factors.     

Comparison between the Hybrid Capture II test and a PCR-based human papillomavirus detection method for diagnosis and posttreatment follow-up of cervical intraepithelial neoplasia

Human papillomavirus (HPV) infection is the major cause of cervical cancer and its precursor, cervical intraepithelial neoplasia (CIN), and HPV testing has therefore been proposed for improved triaging and follow-up of women treated for CIN. We compared two common HPV DNA detection tests (Hybrid Capture II [HCII] and PCR-enzyme immunosorbent assay (EIA) using the primers GP5+/GP6+ followed by HPV typing with reverse dot blot hybridization) for sensitivity and specificity for detection of CIN and of CIN recurrence after treatment. Two hundred and thirty-nine women referred to the Department of Obstetrics and Gynaecology in V?ster?s, Sweden, were enrolled because of atypical Pap smears; 177 of these were later treated for dysplasia by conization or loop diathermy. Samples for HPV DNA testing were taken before and 4 to 6 months after treatment. There was substantial agreement between the HCII and PCR-EIA (kappa, 0.70 before treatment and 0.72 after treatment). The sensitivity for histopathologically confirmed CIN III was 100.0% for PCR-EIA and 95.6% for HCII. For patients with CIN II or worse (CIN II+), the sensitivities were 92.9% (PCR-EIA) and 91.8% (HCII). The specificities for CIN II+ in the pretreatment setting were 30.4% for PCR-EIA and 24.1% for HCII. After treatment, the sensitivities for CIN III in cytology were 100.0% by both methods, and for CIN II+, sensitivities were 80.0% by both methods. The specificities for CIN II+ in the posttreatment setting were 83.5% for PCR and 85.4% for HCII. In conclusion, the sensitivities of both PCR-EIA and HCII are high and almost equal, suggesting that both methods are suitable as tools for detection and posttreatment follow-up of CIN II-III.     

High-risk HPV presence in cervical specimens after a large loop excision of the cervical transformation zone: significance of newly detected hr-HPV genotypes

Large loop excision of the cervical transformation zone (LLETZ) is a well-established treatment for high-grade cervical intraepithelial neoplasia. It has even been postulated that LLETZ is responsible for the elimination of the infectious agent, human papillomavirus (HPV), causing the lesion. Most studies on HPV detection after LLETZ have focused on the persistence of high-risk (hr-) HPV to identify women at risk for residual or recurrent disease. Therefore, the appearance and significance of hr-HPV types newly detected after surgical treatment has not been studied extensively so far. The presence of hr-HPV in 85 high-grade squamous cervical LLETZ biopsies and in the first follow-up smear was determined. In 80 (94%) of the LLETZ biopsies hr-HPV was detected in contrast to 30 (35%) hr-HPV positive follow-up scrapes. Twenty of the 80 hr-HPV positive women (25%) had the same hr-HPV genotypes in their follow-up cervical smears as was found in the corresponding biopsies. In the follow-up smear of 13 women a new hr-HPV genotype was detected and HPV 18 was newly detected in 8 of them. The remarkably high presence of newly detected HPV 18 genotypes may argue for a release or re-activation of this virus from proximal layers of the cervical canal incised during surgery.     

Human Papillomavirus genotype testing combined with cytology as a ‘test of cure’ post treatment: The importance of a persistent viral infection

Background

Human Papillomavirus (HPV) testing has been evaluated as a test of cure in patients following treatment of high-grade cervical intraepithelial neoplasia (CIN2+). Studies show that women who are HPV and cytology negative post treatment can be safely returned to routine recall. The management strategy for HPV positive women requires confirmation.

Objective

To evaluate the clinical utility of the PapilloCheck^® genotyping assay for predicting disease recurrence in a test of cure setting.

Study design

Ninety-eight women (19–52 years) treated for CIN2+ by large loop excision of the transformation zone (LLETZ) were evaluated with samples taken before and 6 months after treatment for HPV testing. Cytology and histology were available from recruitment until 24 months post treatment.

Results

Recurrent disease was evident in 4% of patients with 2 cases low-grade and 2 cases of high-grade disease. In women with no disease recurrence, 40% (95% CI 30.42–51.05%) were high risk (HR) HPV negative post LLETZ. Both cases with high-grade disease had persistent HPV16 infection. Genotyping before and after treatment revealed 83% (95% CI 75.74–88.78%) of total viral infections were cleared and 17% (95% CI 11.22–24.26) viral infections persisted. Post treatment, combined cytology and HPV test results predicted CIN2+ with 100% sensitivity, 91.7% specificity, 100% NPV and 20% PPV and measuring viral persistence marginally increased specificity and PPV.

Conclusion

Post treatment, cytology combined with a single HR HPV test has high sensitivity and specificity for predicting disease recurrence. HPV genotyping before and after LLETZ identifies persistent viral infections and could help refine patient management.     

High frequency of multiple HPV types in cervical specimens from Danish women

Genital human papillomavirus infection (HPV) is common and usually harmless. However, chronic cervical infection with high‐risk HPV types can cause cell changes that may eventually lead to cancer. To determine the frequency of individual HPV types among mixed infections, we examined the type distribution among cervical specimens from more than 1000 Danish women. We also examined the HPV type distribution and the frequency of single and multiple HPV types for specimens from 113 women who underwent conization and were diagnosed with cervical intraepithelial neoplasia grade II or worse (CIN2+). Using microarray technology, we found that 49% of the HPV‐positive patients were infected with multiple HPV types. Among the CIN2+ diagnosed women, this frequency was 41%. The most frequently found high‐risk HPV type was HPV‐16, which was found in 25% of the HPV‐positive cervical specimens. Among the HPV positive CIN2+ diagnosed women, 48% were HPV‐16 positive. Women younger than 30 years of age had a higher frequency of multiple infections (61%) than women older than 30 years (39%). We conclude that cervical infection with multiple HPV types is common among women in all age groups and among women with or without the diagnosis of CIN2+.     

Relationship of P16 and Ki67 in recurrence of HPV infection and cervical intraepithelial neoplasia

This study aimed to investigate the association of P16 and Ki67 expression in cervical conization with postoperative HPV reinfection and cervical intraepithelial neoplasia. This study retrospectively enrolled patients from January 2012 to December 2013. Patients with negative margins were followed up for 2 years to evaluate the correlation between Ki67 and p16 expression levels in the conization of patients with HPV persistence encountering infection or re-infection and CIN recurrence. The positive expression of p16 and Ki67 was significantly correlated with disease progression (P<0.05). p16 and Ki67 expression was chosen, and results showed that positive expression of p16 and ki67 proteins was a risk factor of disease progression (OR=5.3, 95% CI 1.177~24.365, P=0.042; OR=5.1, 95% CI 1.162~22.387, P=0.031, respectively). Results indicated that routine staining for p16 and Ki67 has clinically significant meaning in guiding disease progress and prognosis at follow-up.     

Is the human papillomavirus test in combination with the Papanicolaou test useful for management of patients with diagnoses of atypical squamous cells of undetermined significance/low-grade squamous intraepithelial lesions?

OBJECTIVE: To determine whether human papillomavirus (HPV) testing is useful in the evaluation of patients diagnosed with atypical squamous cells of undetermined significance (ASCUS)/low-grade squamous intraepithelial lesion (LSIL) and whether the HPV test is appropriate as an alternative screening method. DESIGN: The results of Papanicolaou (Pap) tests and subsequent hybrid capture tube (HCT) II tests for high-risk-type HPV were analyzed for 457 patients. Among these tests, 208 histologic diagnoses were made and correlated with the results of Pap and HPV tests. The sensitivity and specificity of the Pap test, HPV test, and the combined method of Pap and HPV tests to detect cervical intraepithelial neoplasia (CIN) 2/3 and all CIN were also measured. RESULTS: Sixty (63.8%) of 94 women with LSIL and 31 (26.3%) of 118 women with ASCUS tested positive for high-risk HPV. The sensitivity values for Pap tests in detecting all cases of CIN and CIN 2/3 were 91.4% and 92.9%, respectively. The sensitivity values of HCT II tests using the high-risk probe for detecting all cases of CIN and CIN 2/3 were 62.6% and 88.1%, respectively. Biopsies confirmed that 10 (22.7%) of 44 LSIL patients with high-risk HPV had CIN 2/3, but only 1 (4.5%) of 22 LSIL patients without high-risk HPV had CIN 2/3. CONCLUSION: Testing for high-risk HPV with the HCT II test is useful in the detection of CIN 2/3 in LSIL groups and in the selection of patients for colposcopy in ASCUS groups, but it is not suitable for cervical cancer screening tests.     

Anyplex II HPV28 detection and Anyplex II HPV HR detection assays are highly concordant with other commercial assays for detection of high-risk HPV genotypes in women with high grade cervical abnormalities

Purpose: to evaluate the performance of Anyplex II HPV28 and HPV HR Detection assays against the EuroArray HPV, Cobas 4800 HPV (Cobas), HPV Amplicor (Amp), Linear Array HPV (LA) and Hybrid Capture 2 (HC2) in detection of high-risk HPV (HR-HPV) from liquid-based cervical cytology samples. Methods: cervical specimens from 404 women undergoing management of high-grade cytological abnormality were evaluated by Anyplex II HPV28 and HPV HR Detection assays for detection of HR-HPV genotypes and prediction of histologically-confirmed cervical intraepithelial neoplasia grade 2 or higher (≥CIN2). The results were compared to EuroArray, HC2, Cobas, Amp, and LA. Results: specimens were evaluated from 404 women with an average age of 30 years, including 336 with a histological diagnosis of?≥?CIN2 and 68 with?≤?CIN1. Concordance of HR-HPV detection between Anyplex II HPV28 and other genotyping assays was 94.79 % (κ?=?0.84; EuroArray) and 97.27 % (κ?=?0.91; LA); and between Anyplex II HPV HR and other HR-HPV detection assays was 86.35 % (κ?=?0.62; HC2), 96.03 % (κ?=?0.87; Cobas) and 96.77 % (κ?=?0.89; Amp). Using HR-HPV detection for prediction of?≥?CIN2 by Anyplex II HPV28 and HPV HR, sensitivity (90.18, 95 % CI 86.48–93.14; 90.77, 95 % CI 87.16–93.65) and specificity (both 67.16, 95 % CI 54.60–78.15) were not significantly different to the other HPV assays tested, with one exception. Both Anyplex assays had significantly higher sensitivity than HC2 (p?<?0.0001), with a specificity of 96 % (p?>?0.05) of HC2 in this high-risk population. Conclusions: both Anyplex II HPV detection assays were concordant with other commercial assays for HR-HPV detection, with comparable sensitivity and specificity for?≥?CIN2 detection.     

Comparative study of the cervista and hybrid capture 2 methods in detecting high‐risk human papillomavirus in cervical lesions

High‐risk human papillomavirus (HR HPV) testing is important for the follow‐up of patients with cytological abnormalities. This study was undertaken to compare the clinical value of the Cervista and hybrid capture 2 (HC2) tests for detection of HR HPV in cervical lesions. Overall 439 cervical specimens with abnormal cytology and 22 normal cervical specimens were subjected to the Cervista and HC2 tests. HPV positivity and its predictive value for high‐grade cervical lesions were assessed. The Cervista and HC2 tests showed comparable HR HPV detection rates in women with all cytological and histological diagnoses, with a positive and negative percent agreement of 90.8% and 64.5%, respectively. The two methods had a same sensitivity of 90% in detecting CIN II or greater cervical lesions, while the specificity for the Cervista test and HC2 assay was 47% and 43%, respectively. The positive rate for the Cervista assay probe set A9 increased with the histological severity, ranging from 25.0% in normal specimens to 69.5% in high‐grade lesions. In conclusion, the clinical performance for the Cervista test is as excellent as the HC2 test in detecting HR HPV and predicting high‐grade cervical lesions. Diagn. Cytopathol. 2014;42:213–217. © 2013 Wiley Periodicals, Inc.     

Performance of proex c and pretect hpv‐proofer e6/e7 mrna tests in comparison with the hybrid capture 2 hpv dna test for triaging ascus and lsil cytology

The clinical usefulness of the ProEx C (Becton Dickinson) and PreTect HPV‐Proofer E6/E7 mRNA tests (Proofer; Norchip) for the triage of ASCUS and LSIL cytology was determined in comparison with the Hybrid Capture 2 HPV DNA test (HC2; Qiagen). The study population consisted of women with a history of abnormal cytology referred to colposcopy. Histology‐confirmed CIN 2+ served as the disease endpoint. The study was based on 1,360 women (mean age 30.7 years), of whom 380 had CIN 2+. Among 315 with ASCUS (CIN 2+, n = 67), the sensitivities of ProEx C, Proofer, and HC2 to detect CIN 2+ were, 71.6, 71.6, and 95.5%, respectively, with a corresponding specificity of 74.6, 74.2, and 35.1%. Among 363 with LSIL (CIN 2+, n = 108), the sensitivities of ProEx C, Proofer, and HC2 were, 67.6, 74.1, and 96.3%, respectively, with a corresponding specificity of 60, 68.2, and 18.4%. Among 225 HC2‐positive ASCUS (CIN 2+, n = 64), 105 tested positive by ProEx C, reducing colposcopy referral by 53.3% and detecting 71.9% of CIN 2+; Proofer was positive in 112/225, reducing colposcopy referral by 50.2% and detecting 75.0% of CIN 2+. Among 312 HC2‐positive LSIL (CIN 2+, n = 104), 160 tested positive by ProEx C, reducing coloposcopy referral by 48.7% and detecting 66.3% of CIN 2+; Proofer was positive in 159/312, reducing colposcopy referral by 49.0% and detecting 75.0% of CIN 2+. In conclusion, both ProEx C and Proofer have a similar performance profile with a significantly higher specificity but lower sensitivity than HC2 for the detection of CIN 2+. Consequently, although they can reduce colposcopy referral, they will miss a proportion of CIN 2+ cases. This is a major limitation and should be taken into account if these tests are considered for ASCUS or LSIL triage. Diagn. Cytopathol. 2013;41:767–775. © 2013 Wiley Periodicals, Inc.     

Increased detection of clue cells in smears from cervical intraepithelial lesions with reduced expression of COX-2

The relation between the detection of clue cells in cervical smears of women with CIN and the expression of COX-2 in these lesions were determined. Samples from 228 women, treated due to CIN and who underwent cervical conization, were obtained. Hybrid Capture II and Pap smear samples were collected immediately before performing conization. Pathological diagnoses were 11 (5%) normal cervix, 35 (15%) CIN1, 31 (14%) CIN2, and 151 (66%) CIN3. COX-2 immunoreactivity grading on the pathological specimens was based on the German ImmunoReactive score. In cervical smears, 20 fields (40x) were examined, each of them with a minimum count of 10 epithelial cells. When 20% or more of clue cells were detected the sample was considered positive for clue cells. The prevalence of clue cells was similar across histological strata (P = 0.42). Although the expression of COX-2 did not differ in lesions with varying severities (P = 0.24), there was a negative association between the expression of COX-2 and the presence of clue cells in Pap smear (OR = 0.4; 95% CI = 0.2-0.9): only 12% of women with moderate and strong expression of COX-2 had clue cells in their smears, contrasted to 22% of those with negative and weak expression of COX-2. HPV infection was associated in a borderline manner to the expression of COX-2 (P = 0.04; OR = 2.3 95% CI = 1.0-5.4). The reduced expression of COX-2 in CIN specimens may suggest that clue cells interfere with the inflammatory component of the carcinogenic process that lead to CIN.     

Clinical significance of HPV DNA cotesting in Korean women with ASCUS or ASC‐H

The purpose of this study was to evaluate the clinical significance of Human papillomavirus (HPV) DNA cotesting in Korean women with abnormal Papanicolaou (Pap) smear results based on colposcopic pathology. A total of 1012 women underwent liquid‐based Pap smears and hybrid capture II HPV DNA tests followed by colposcopy at the Korea University Hospital from January 2007 to May 2012. Of these women, 832 women were included in this retrospective study. The mean patient age was 45.4 ± 13.7 years (range:15–80). The distribution of Pap smear results was normal (4.7%), atypical squamous cells of uncertain significance (ASCUS) (42.1%), low‐grade squamous intraepithelial lesion (26.8%), ASC‐H (7.0%), and high‐grade squamous intraepithelial lesion (HSIL) (19.5%). In women with ASCUS, none of the 87 HPV‐negative had ≥cervical intraepithelial neoplasia (CIN2) (P < 0.001). In women with ASC‐H, only one out of 17 HPV‐negative vs. 14 out of 41 HPV‐positive had ≥CIN2 (P = 0.025). In patients with HSIL, 54.5% of HPV‐negative had ≥CIN2, as compared to 80.8% of HPV‐positive with ≥CIN2 (P = 0.039). Patients were further analyzed by age groups: <30 and ≥30 years. In HPV‐negative women, there was a significant difference in the ratio of ≥CIN2 (30.8% <30 vs. 4.5% ≥30, P = 0.005). When the HPV DNA test was negative in women ≥30, the risk of ≥CIN2 was significantly lower (P < 0.001). HPV DNA cotesting in women with ASCUS and ASC‐H furnish healthcare providers with informative data. There is a lower proportion of ≥CIN2 in HPV‐negative women and a higher proportion of ≥CIN2 in HPV‐positive. When HPV data were further evaluated by age group, the risk of ≥CIN2 was lower in HPV‐negative women, especially in women ≥30. Diagn. Cytopathol. 2014;42:1058–1062. © 2014 Wiley Periodicals, Inc.     

Evaluation of any or type-specific persistence of high-risk human papillomavirus for detecting cervical precancer

High-risk human papillomavirus (HR-HPV) testing is increasingly important. We therefore examined the impact on accuracy of repeated versus one-time testing, type-specific versus pooled detection, and assay analytic sensitivity. By using a nested case-control design from the ASCUS-LSIL Triage Study, we selected women with incident cervical intraepithelial neoplasia grade 2 or grade 3 (CIN2/3; n = 325) and a random sample of women with 相似文献   

宫颈上皮内瘤变及其治疗对妊娠的影响

宫颈鳞状上皮内瘤变是一种和HPV感染有关的宫颈癌前病变。根据病变程度分为低度和高度鳞状上皮内病变,其中低度病变包括HPV感染和C IN1,高度病变包括C IN2~3。HPV感染和宫颈上皮内瘤变是一种生育年龄妇女常见的妇科疾病,HPV感染、宫颈病变本身及其治疗对妊娠的影响倍受关注。HPV感染在妊娠期间可能增加,经阴道分娩者新生儿暴露于HPV的机会增多,尚不能下结论对所有HPV感染者均采用剖宫产的分娩方式。妊娠期间发现C IN1,可以观察并产后随访。如果为C IN2~3,妊娠可能不会加重病变程度,但对阴道镜检查不满意者或高度怀疑浸润癌者应在孕期明确诊断,可于妊娠中期行宫颈锥切术。妊娠中期行宫颈锥切术可能使剖宫产率增加。C IN保守治疗对于患者受孕能力无显著的影响;宫颈冷刀锥切及LEEP锥切可能增加早产率,早产率的增加可能和胎膜早破的发生有关。     

Human papillomavirus (HPV) DNA triage of women with atypical squamous cells of undetermined significance with cobas 4800 HPV and Hybrid Capture 2 tests for detection of high-grade lesions of the uterine cervix

The triage of women with high-risk (HR) human papillomavirus (HPV)-positive smears for atypical squamous cells of undetermined significance (ASC-US) to colposcopy is now an integrated option in clinical guidelines. The performance of cobas 4800 HPV and that of Hybrid Capture 2 (HC2) for HR HPV DNA detection in cervical samples in PreservCyt were compared in 396 women referred to colposcopy for ASC-US. Of these, 316 did not have cervical intraepithelial neoplasia (CIN), 47 had CIN1, 29 had CIN2 or CIN3 (CIN2+), and 4 had CIN of unknown grade. HR HPV was detected in 129 (32.6%) and 149 (37.6%) samples with HC2 and cobas 4800 HPV, respectively (P = 0.15). The clinical sensitivities and specificities for detecting CIN2+ were 89.7% (95% confidence interval [CI], 72.8 to 97.2%) and 66.7% (95% CI, 61.7 to 71.3%) with cobas 4800 HPV and 93.1% (95% CI, 77.0 to 99.2%) and 72.2% (95% CI 67.4 to 76.5%) with HC2. The performance of cobas 4800 HPV was similar to that of HC2 for identifying women with ASC-US who would benefit the most from colposcopy.