Evaluation of partial genotyping with HPV16/18 for triage of HPV positive, cytology negative women in the COMPACT study.

OBJECTIVE: While cytology-based screening programs have significantly reduced mortality and morbidity from cervical cancer, the global consensus is that primary human papillomavirus (HPV) testing increases detection of high-grade cervical intraepithelial neoplasia (CIN) and invasive cancer. However, the optimal triage strategy for HPV+ women to avoid over-referral to colposcopy may be setting specific. We compared absolute and relative risk (RR) of >CIN2/3 within 12 months of a negative cytologic result in women HPV16/18+ compared to those with a 12-other high-risk HPV (hrHPV) genotype to identify women at greatest risk of high-grade disease and permit less aggressive management of women with other hrHPV infections. METHODS: Participants were 14,160 women aged 25-69 years with negative cytology participating in the COMparison of HPV genotyping And Cytology Triage (COMPACT) study. Women who were HPV16/18+ were referred to colposcopy. Those with a 12-other hrHPV type underwent repeat cytology after 6 months and those with >abnormal squamous cells of undetermined significance went to colposcopy. RESULTS: Absolute risk of >CIN2 in HPV16/18+ women was 19.5% (95% CI=12.4%-29.4%). In women 25-29 years and HPV16+ it was 40.0% (95% CI=11.8%-76.9%). Absolute risk of >CIN3 in women HPV16/18+ was 11.0% (95% CI=5.9%-19.6%). For women 30-39 years and HPV16+ it was 23.1% (95% CI=5.0%-53.8%). Overall risk of >CIN2, >CIN3 in women with a 12-other hrHPV HPV type was 5.6% (95% CI=3.1%-10.0%) and 3.4% (95% CI=1.6%-7.2%) respectively. RR of >CIN2, >CIN3 in HPV16/18+ vs. 12-other hrHPV was 3.5 (95% CI=1.7-7.3) and 3.3 (95% CI=1.2-8.8), respectively. CONCLUSION: Primary HPV screening with HPV16/18 partial genotyping is a promising strategy to identify women at current/future risk of >CIN2 in Japan without over-referral to colposcopy. TRIAL REGISTRATION: Trial Registration: UMIN Clinical Trials Registry Identifier: UMIN000013203.

Comparison of human papillomavirus genotyping and cytology triage, COMPACT Study: Design, methods and baseline results in 14 642 women.

Although cytology-based screening programs have significantly reduced mortality and morbidity from cervical cancer, the global consensus is that primary human papillomavirus (HPV) testing for cervical screening increases detection of high-grade cervical intraepithelial neoplasia (CIN) and invasive cancer. However, the optimal triage strategy for HPV-positive women to avoid over-referral to colposcopy may be setting specific. As Japan requires data that have been generated domestically to modify screening guidelines, we conducted a 3-year prospective study, COMparison of HPV genotyping And Cytology Triage (COMPACT), to evaluate the potential role of HPV16/18 partial genotyping and cytology for primary HPV screening. In total, 14 642 women aged 20 to 69 years undergoing routine screening at 3 centers in Hokkaido were enrolled. Conventional cytology and HPV testing were carried out. Women with abnormal cytology or HPV16/18 positivity underwent colposcopy. Those with 12 other high-risk (hr) HPV types underwent repeat cytology after 6 months. Primary study endpoints were detection of high-grade cervical disease defined as CIN2/CIN3 or greater as determined by consensus pathology. Prevalence of cytological abnormalities was 2.4%. hrHPV, HPV 16, and HPV 18 were detected in 4.6%, 0.9%, and 0.3% of women, respectively. HPV16/18 were detected in all (8/8) invasive cervical cancers and in all (2/2) adenocarcinomas in situ. Both cytological abnormalities and hrHPV positivity declined with increasing age. This is the first Japanese study to investigate the role of partial genotyping and cytology in an HPV-based screening program. Results should help policy-makers develop guidelines for future cervical screening programs and management of cervical abnormalities based on HPV genotype.

Relationship between erythropoietin levels both in cord serum and amniotic fluid at birth and abnormal fetal heart rate records.

BACKGROUND: Our data in rats suggest that an elevated amniotic fluid erythropoietin (EPO) level at birth indicates antepartum fetal hypoxia. However, the short gestation period in rats does not permit a direct comparison of our data with humans. METHODS: We conducted a retrospective study of the relationship between EPO levels at birth and abnormal fetal heart rate (FHR) records in 113 infants. RESULTS: Among the cesarean section group, the cord serum and amniotic fluid EPO levels in the infants with antepartum abnormal FHR records were significantly higher than those in the control infants. Among the vaginal delivery group, the cord serum EPO levels in the infants with intrapartum abnormal FHR records was significantly higher than that in the control infants. The EPO levels in either cord serum and amniotic fluid discriminated between infants with antepartum abnormal FHR records. The control infants had a sensitivity of 83% and a specificity of 96%. Six of the seven infants with abnormal EPO levels in both cord serum and amniotic fluid had symptoms of prolonged fetal hypoxia. Five infants with abnormal EPO levels in only cord serum had symptoms of acute fetal hypoxia before birth. Four of the 14 infants with abnormal EPO levels at birth had poor outcomes in the neonatal period. CONCLUSIONS: We concluded that EPO levels in both cord serum and amniotic fluid at birth are valuable for determining the timing of fetal hypoxia and may predict the outcome in the neonatal period.