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.     

A National Survey of Canadian Adults on HPV: Knowledge,Attitudes, and Barriers to the HPV Vaccine

ObjectiveIdentifying human papillomavirus (HPV) vaccination motivators and barriers among adults could lead to new approaches to improve HPV vaccination rates in non-pediatric populations. This Canadian survey aimed to assess current knowledge of, attitudes towards, and barriers to the HPV vaccine among the general public.MethodsAn online panel was used to survey HPV unvaccinated women (n = 802) and vaccinated women (n = 250) 18 to 45 years old, as well as 18- to 26-year-old men (n = 200), in May and June 2016. A 16-item questionnaire collected data on sociodemographic factors, health-seeking behaviours, knowledge of HPV infection and its consequences, and the HPV vaccine. Data were stratified by sex and by vaccination status among women.ResultsThe majority of individuals somewhat or strongly agreed that vaccination is an important aspect of disease prevention (vaccinated women, 93%; unvaccinated women, 85%; and men, 59%). However, a high proportion of patients were concerned about vaccine safety (vaccinated women, 26%; unvaccinated women, 40%; and men, 36%). Moreover, 58% to 61% of participants were generally cautious about taking any vaccine. The number one reported barrier to vaccination was not having a recommendation from a doctor (38%). Cost was seen as a barrier by only 18% to 20% of participants.ConclusionCanadian participants show a broad diversity in HPV knowledge and regarding barriers to vaccination. The youngest populations (vaccinated women and men) showed higher levels of knowledge regarding HPV.     

National trends,outcomes, and costs of radiation therapy in the management of low- and high-intermediate risk endometrial cancer

ObjectiveTo assess treatment patterns, outcomes, and costs for women with low-(LIR) and high-intermediate risk endometrial cancer (HIR) who are treated with and without adjuvant radiotherapy.MethodsAll patients with stage I endometrioid endometrial cancer who underwent surgery from 2000 to 2011 were identified from the SEER-Medicare database. LIR was defined as G1–2 tumors with <50% myometrial invasion or G3 with no invasion. HIR was defined as G1–2 tumors with ≥50% or G3 with <50% invasion. Patients were categorized according to whether they received adjuvant radiotherapy (vaginal brachytherapy [VBT], external beam radiotherapy [EBRT], or both) or no radiotherapy. Outcomes were analyzed and compared (primary outcome was overall survival).Results10,842 patients met inclusion criteria. In the LIR group (n = 7609), there was no difference in 10-year overall survival between patients who received radiotherapy and those who did not (67% vs 65%, adjusted HR 0.95, 95% CI 0.81–1.11). In the HIR group (n = 3233), patients who underwent radiotherapy had a significant increase in survival (60% vs 47%, aHR 0.75, 95% CI 0.67–0.85). Radiotherapy was associated with increased costs compared to surgery alone ($26,585 vs $16,712, p < .001). Costs for patients receiving VBT, EBRT, and concurrent VBT/EBRT were $24,044, $27,512, and $31,564, respectively (p < .001). Radiotherapy was associated with an increased risk of gastrointestinal (7 vs 4%), genitourinary (2 vs 1%), and hematologic (16 vs 12%) complications (p < .001).ConclusionsRadiotherapy was associated with improved survival in women with HIR, but not in LIR. It also had increased costs and a higher morbidity risk. Consideration of observation without radiotherapy in LIR may be reasonable.     

A randomized phase II study of cabozantinib versus weekly paclitaxel in the treatment of persistent or recurrent epithelial ovarian,fallopian tube or primary peritoneal cancer: An NRG Oncology/Gynecologic Oncology Group study

IntroductionCabozantinib is a receptor tyrosine kinases inhibitor that targets MET (c-MET), VEGF receptor 2 (VEGFR2), RET, AXL, KIT, FLT-3, and TIE-2 and previously showed promising single agent activity in recurrent ovarian cancer.MethodsThis was an open label, 1:1 randomized study of cabozantinib 60 mg orally (PO) daily versus weekly paclitaxel 80 mg/m² given 3 out of 4 weeks (NCT01716715); 111 patients were enrolled. Eligibility included persistent or recurrent epithelial ovarian, fallopian tube, or primary peritoneal carcinoma and at least one but no >3 prior chemotherapy regimens.ResultsMedian PFS was similar for both treatment groups and was 5.3 months for cabozantinib and 5.5 months for weekly paclitaxel (HR 1.11 (90% CI 0.77–1.61, p = 0.64)). Secondary analyses of overall survival (OS) and event free survival (EFS) showed that cabozantinib did not perform as well as weekly paclitaxel. Median OS for cabozantinib was 19.4 months and was not reached for weekly paclitaxel (HR 2.27 (90% CI 1.17–4.41, p = 0.04). EFS was also worse in the cabozantinib arm, 3.5 months, compared to weekly paclitaxel at 5.0 months (HR 1.81 (90% CI 1.24–2.63, p = 0.01). Overall response rate (ORR) was less for cabozantinib compared to weekly paclitaxel (7% versus 24.1%). Gastrointestinal toxicities, specifically nausea, diarrhea, and abdominal pain were worse in the cabozantinib arm.ConclusionsMedian PFS was similar for cabozantinib and weekly paclitaxel. However, OS, EFS, and ORR were worse for cabozantinib compared to weekly paclitaxel. Cabozantinib given at this dose and schedule cannot be recommended as a treatment for recurrent ovarian cancer.     

HPV genotype profile in a Norwegian cohort with ASC-US and LSIL cytology with three year cumulative risk of high grade cervical neoplasia

Objective

To explore the HPVgenotype profile in Norwegian women with ASC-US/LSIL cytology and the subsequent risk of high-grade cervical neoplasia (CIN 3 +).

Tumor-associated macrophage expression of PD-L1 in implants of high grade serous ovarian carcinoma: A comparison of matched primary and metastatic tumors

Objective

Data on PD-L1 expression in high grade serous ovarian carcinoma (HGSOC) is mixed. Some studies report robust tumor staining and others identify expression limited to tumor-associated macrophages (TAM). TAM PD-L1 expression is induced in HGSOC metastatic implants from patients who have undergone chemotherapy. However, it is unclear whether TAM acquisition of PD-L1 plays a role in treatment naïve tumors. We investigated PD-L1 expression in primary ovarian tumors and matched metastatic implants from predominantly treatment-naïve HGSOC.