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.

OBJECTIVETo identify the ankyrin-B gene mutations that cause long QT syndrome (LQTS) and determine the prevalence of such mutations in Japanese patients with LQTS.

METHODSWe conducted a search for ankyrin-B gene mutation in 78 unrelated patients with LQTS (28 males and 50 females, aged 2 to 89 years). With informed consent from all the subjects and/or their parents, genomic DNA was purified from the white blood cells of the patients and amplified using polymerase chain reaction (PCR). Single-strand conformational polymorphism (SSCP) analysis of the amplified DNA was performed to screen for mutations and aberrant SSCP products were isolated and sequenced by dye terminator cycle sequencing method using an automated fluorescent sequencer. PCR and restriction fragment length polymorphism (PCR-RFLP) analysis was carried out to further confirm the missense mutations by comparison with samples from 150 normal healthy individuals.

RESULTSWe identified a T to A transition mutation at position 4,603 in exon 40, resulting in the substitution of arginine for a tryptophan at amino acid residue 1,535 (W1535R) in the regulatory domain of 220-kD ankyrin-B, which is a highly conserved domain shared by different species.

CONCLUSIONThis novel missense mutation in the ankyrin-B gene may be a cause of type 4 LQTS. Ankyrin-B gene mutation might not play the major role in LQTS in Japanese.

Adolescent ; Adult ; Aged ; Aged, 80 and over ; Amino Acid Substitution ; Ankyrins ; genetics ; Base Sequence ; Child ; Child, Preschool ; Exons ; Female ; Humans ; Long QT Syndrome ; genetics ; Male ; Middle Aged ; Molecular Sequence Data ; Mutation, Missense ; Point Mutation