Timing of HPV16-E6 antibody seroconversion before OPSCC: findings from the HPVC3 consortium.

BACKGROUND: Human papillomavirus type 16 (HPV16)-E6 antibodies are detectable in peripheral blood before diagnosis in the majority of HPV16-driven oropharyngeal squamous cell carcinoma (OPSCC), but the timing of seroconversion is unknown. PATIENTS AND METHODS: We formed the HPV Cancer Cohort Consortium which comprises nine population cohorts from Europe, North America and Australia. In total, 743 incident OPSCC cases and 5814 controls provided at least one pre-diagnostic blood sample, including 111 cases with multiple samples. Median time between first blood collection and OPSCC diagnosis was 11.4 years (IQR = 6-11 years, range = 0-40 years). Antibodies against HPV16-E6 were measured by multiplex serology (GST fusion protein based Luminex assay). RESULTS: HPV16-E6 seropositivity was present in 0.4% of controls (22/5814; 95% CI 0.2% to 0.6%) and 26.2% (195/743; 95% CI 23.1% to 29.6%) of OPSCC cases. HPV16-E6 seropositivity increased the odds of OPSCC 98.2-fold (95% CI 62.1-155.4) in whites and 17.2-fold (95% CI 1.7-170.5) in blacks. Seropositivity in cases was more frequent in recent calendar periods, ranging from 21.9% pre-1996 to 68.4% in 2005 onwards, in those with blood collection near diagnosis (lead time <5 years). HPV16-E6 seropositivity increased with lead time: 0.0%, 13.5%, 23.7%, and 38.9% with lead times of >30 years (N = 24), 20-30 years (N = 148), 10-20 years (N = 228), and <10 years (N = 301 cases) (p-trend < 0.001). Of the 47 HPV16-E6 seropositive cases with serially-collected blood samples, 17 cases seroconverted during follow-up, with timing ranging from 6 to 28 years before diagnosis. For the remaining 30 cases, robust seropositivity was observed up to 25 years before diagnosis. CONCLUSIONS: The immune response to HPV16-driven tumorigenesis is most often detectable several decades before OPSCC diagnosis. HPV16-E6 seropositive individuals face increased risk of OPSCC over several decades.

Effect of dietary change on the return of hypertension after withdrawal of prolonged antihypertensive therapy (DISH). Dietary Intervention Study of Hypertension.

The possibility exists that dietary modification may increase the number of patients who remain normotensive after drug withdrawal. In an effort to resolve this question, former Hypertension Detection and Follow-up Program Stepped Care participants (n = 496) were randomized into four major groups at the end of the programme (greater than 5 years antihypertensive therapy): controls (continue medication); discontinue medication, no dietary intervention; discontinue medication and weight loss; discontinue medication and reduce sodium. Groups 1, 2 and 4 were further divided into obese (greater than or equal to 120% ideal weight, and non-obese groups). The weight reduction group (greater than or equal to 120% ideal weight) lost 10.1 +/- 11 lbs without changing dietary sodium (n = 87). The sodium restriction group reduced urine sodium excretion from 145 to 97 mEq per day (n = 169). Sixty per cent of the weight loss group were normotensive at 56 weeks compared to 35% withdrawn from medication without dietary intervention. The highest 56 weeks success rates were in the mild non-overweight hypertensives on sodium restriction (78%), and the mild overweight hypertensives on weight reduction (72%). Randomization to either weight loss group or sodium restriction group increased the likelihood of remaining off drugs (adjusted odds ratio of 3.43 for the weight group and 2.17 for the sodium group (P less than 0.05). Age, severe hypertension greater than 5 years previous to entry into Dietary Intervention Study of Hypertension (DISH) or need for several drugs increased the chance of failure.