Risk assessment and clinical impact of liquid-based cytology, oncogenic human papillomavirus (HPV) DNA and mRNA testing in primary cervical cancer screening (the FASE study).

OBJECTIVE: New commercial HPV RNA assays require further validation studies in population-based cervical cancer screening settings. To assess the performance of (FDA-approved) APTIMA® HPV Assay (AHPV), Hybrid Capture 2 (HC2), in-house PCR genotyping, and ThinPrep LBC in population-based screening, stratified by three histological gold standards. STUDY DESIGN: A multi-center trial in 5006 women undergoing routine screening in France was designed to compare the absolute and relative risks of diagnosing CIN3+ and CIN2+ lesions by different diagnostic tests. RESULTS: Reproducibility between the primary and second pathology reading was excellent for CIN3+ and CIN2+ endpoints (Cohen's kappa 0.948 and 0.854). Absolute risks (PPV) of different tests (AHPV, HC2, PCR genotyping, LBC) in diagnosing CIN2+ (15-20%) and CIN3+ (4-6%) were similar for the first, second, and consensus pathology readings. The relative risks of diagnosing these lesions by the four tests were also similar when the first, second or third pathology readings were employed. AHPV had the highest absolute risk of both histological endpoints, and detects 5% to 15% more CIN3+ and CIN2+ lesions, respectively, than LBC. Compared with HC2 assay, the relative risk of AHPV is 24% to 29% higher, with a significant difference in CIN2+ detection. With LBC as reference, AHPV had the best sensitivity/specificity balance measured by AUC (area under ROC curve) comparison test (significant for CIN2+), and the colposcopy referral rate (9.2%) comparable to that of LBC (8.7%). CONCLUSIONS: These data corroborate the suitability of AHPV for the primary cervical cancer screening.

Evaluation of oncogenic human papillomavirus RNA and DNA tests with liquid-based cytology in primary cervical cancer screening: the FASE study.

The APTIMA HPV Assay (AHPV) allows detection of 14 high-risk human papillomavirus (HPV) RNA types in cervical specimens. Until present, the assay has been compared to HPV DNA tests only in triage settings. Herein, we compare AHPV with a DNA assay (Hybrid Capture 2; HC2) and liquid-based cytology (LBC; using PreservCyt ThinPrep liquid Pap) in a screening setting (French APTIMA screening evaluation [FASE] study). Women (N = 5,006) aged 20-65 were screened by gynecologists in 17 private practices in Paris, France. One cervical specimen was collected and tested with LBC, AHPV and HC2 assays. Women were referred to colposcopy if they were ASC-US+ in LBC or HPV positive in either HPV assay. To control for verification bias, a random group (14%) with normal LBC and dually HPV negative tests underwent colposcopy. Data from 4,429 women were analyzed. Sensitivity, specificity and predictive values were calculated for the three tests. AHPV and HC2 were highly sensitive for CIN2+ (92.0% and 96.7%) and CIN3+ (95.7% and 95.3%) detection and much more sensitive than LBC (69.1% for CIN2+ and 73.3% for CIN3+). Specificity of AHPV was higher than that of HC2, but similar to that of LBC (p < 0.001). Combining LBC with either HPV test slightly increased sensitivity but compromised specificity. AHPV assay is both specific and sensitive for the detection of high-grade precancerous lesions and may be considered as an option for routine cervical cancer screening for women over 20 years of age.

The role of Pipelle Mark II sampling in endometrial disease diagnosis.

OBJECTIVE: To evaluate the feasibility and accuracy of Pipelle Mark II sampling (designed for combined cytology and histology testing) in the diagnosis of endometrial disease. MATERIALS AND METHODS: A 97 women with abnormal uterine bleeding or intrauterine lesions on ultrasound examination underwent Pipelle Mark II endometrial sampling, followed by diagnostic hysteroscopy. The adequacy of endometrial samples obtained for cytological and histological analysis was assessed. A correlation was established between endometrial cytology, histology and diagnostic hysteroscopy results. Where discrepancies were found, they were compared with the histological results obtained from operative hysteroscopy. RESULTS: The tissue samples obtained for cytological and histological diagnoses were insufficient in 14.4% and 11.3% of patients, respectively. The opposite was found in the group of postmenopausal women (N=52): the tissue samples for cytological and histological diagnoses were insufficient in only 3.8% and 15.4% of cases, respectively. The cytological results corroborated diagnostic hysteroscopy findings and histological results in all cases but 3 (3.6%). Only two cases of endometrial carcinoma were reported in this group of patients, and they were both detected by all three methods. The rate of false positives with endometrial cytological sampling was 3.6%. There were no false negatives. CONCLUSION: Pipelle Mark II endometrial sampling is feasible. It provides adequate samples for histological and/or cytological analysis and reliable results. It reduces the rate of false negative results for endometrial cancer. Pipelle Mark II sampling is particularly useful in postmenopausal women and in women with endometrial atrophy. Other larger studies are necessary to evaluate the efficiency of Pipelle Mark II.

Predictive factors for complete excision and underestimation of one-pass en bloc excision of non-palpable breast lesions with the Intact(®) breast lesion excision system.

OBJECTIVE: Image-guided percutaneous biopsy is the recommended initial diagnostic procedure for suspicious mammographic lesions. This study was conducted to determine the accuracy of the Intact(®) breast lesion excision system (BLES) and to identify predictive factors for complete excision and underestimation. MATERIAL AND METHODS: A prospective study was conducted between January 28, 2008 and April 30, 2009 on 166 biopsy procedures using Intact(®) biopsy device. Diagnoses obtained from biopsy specimen were compared with to final diagnosis on surgical excision specimen. RESULTS: Of the 166 patients, 15 (9%) displayed lesions with cell atypia, 28 (17%) had an intra ductal carcinoma (IDC) and 9 (5%) had an invasive carcinoma. Eight of 15 patients with cell atypia had open surgical excision, and none showed underestimation. All patients with IDC underwent surgical excision: we found an invasive carcinoma in 6 cases (21.4% underestimation) and a complete removal of the lesion by the Intact(®) BLES in 11 cases (39%). All 9 patients with invasive carcinoma had a surgical excision, with 1 complete removal of the lesion by Intact(®) BLES. Multivariate analyses did not identify predictive factors for underestimation; clear margins ≥1mm on biopsy specimen was the only independent predictive factor of complete excision (OR=8.51, p=0.02). CONCLUSIONS: Intact(®) BLES provides a safe alternative to vacuum assisted core needle biopsy (VACNB) with an underestimation rate comparable to those previously reported for VACNB. The high rate of complete removal of the lesions, particularly ISC, offers an interesting perspective of avoiding subsequent excisional surgery for small lesions and thus requires further confirmational study.

Prevalence of type-specific human papillomavirus infection among women in France: Implications for screening, vaccination, and a future generation of multivalent HPV vaccines.

To assess human papillomavirus (HPV) prevalence and genotype distribution by age and cervical cytology/histology status among women undergoing routine gynecological examinations, and to discuss the possible impact on preventive strategies. Liquid-based cytology (LBC) samples were tested for HPV DNA, mRNA, and HPV genotypes. Women with atypical squamous cells of undetermined significance or greater (ASC-US+) and/or at least one positive HPV test were referred to colposcopy. Those with normal colposcopy results had biopsies taken at the 6 and 12 O'clock positions of the normal transformation zone. Of the 5002 women, 515 (10.3%) were <25 and 4487 (89.7%) were ≥25years old. Overall HPV prevalence varied between 10.1% and 16.1% depending on the assay. Risk factors for HPV infection included greater number of recent sexual partners, history of abnormal cervical pathology, age <25years, and smoking. HPV prevalence increased with the cytological and histological severity of cervical lesions. Prevalence of HPV 16/18 was 5.2% and 2.7% in women <25 and ≥25years old, respectively. HPV 16 was the type most strongly associated with a diagnosis of cervical intraepithelial neoplasia grade 3 or higher (CIN3+) (odds ratio=11.64 vs. HPV 16 absent, P<0.001). A high proportion of high-grade cervical lesions (60.6% of genotyping assay-positive CIN2+) were associated with HPV types 31, 33, 45, 52, or 58. These data indicate that almost all young women could benefit from HPV prophylactic vaccination, but confirm the need for continued cervical screening and highlight the potential benefit of future vaccines targeting a wider range of HPV types.

Cervical schistosomiasis as a risk factor of cervical uterine dysplasia in a traveler.

Female genital schistosomiasis (FGS) may be under-recognized in endemic areas as a cause of cervical dysplasia, neoplasia, infertility, and as a facilitator of the transmission of HIV. To the best of our knowledge, few cases of FGS mimicking neoplasia have been reported in travelers. We report a clinical case of a 34-year-old white woman who presented with a severe cervical dysplasia, without any features of human papilloma virus infection, 2 years after bathing in a waterfall, a source of schistosomiasis, in Mali. Schistosomes eggs were found on the conization. Management included conization and medical treatment, resulting in a full clinical and histologic recovery. FGS should be kept in mind as a possible cause of cervical dysplasia in endemic areas. Medical treatment with praziquantel improves this condition.

Detection of human papillomavirus genotypes among high-risk women: a comparison of hybrid capture and linear array tests.

OBJECTIVES: To assess the concordance and performance of 2 different assays in detection of human papillomavirus (HPV) genotypes among women with abnormal Pap smear. STUDY DESIGN: A series of 575 women referred for colposcopy due to an abnormal Pap smear were analyzed with the Linear Array HPV Genotyping test detecting 37 HPV types and compared with Hybrid Capture II (HCII) assay for detection of carcinogenic HPV. Histologic outcomes of cervical intraepithelial neoplasia grade 2 (CIN2) or worse (CIN2+) and CIN3+ were the primary endpoints. Clinical performance, including receiver operating characteristics, was determined for both tests. RESULTS: HCII and linear array (LA) were concordant in 88.1% (433/491; 95% CI 85.3%-91.0%), having a substantial agreement with regular kappa (kappa = 0.70, 95% CI 0.62-0.77) and almost perfect agreement with weighted kappa (ICC = 0.82, 95% CI 0.7-0.85). In detecting CIN2+ and CIN3+, LA is 5% and 6% more sensitive but 9.5% and 8.7% less specific than HCII (area under ROC curve; P = 0.317 and P = 0.875, respectively). CONCLUSIONS: Performance of HCII and LA does not significantly differ in detecting CIN2+ or CIN3+.