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*222. Rhythmic Annual Changes in Cancer Biology Affect Epidemiologic Meaning, the Efficiency of Prevention, Screening and Treatment Strategies

WJM Hrushesky, Dorn VA Medical Center; RB Sothern, College of Biol Sci, Univ of Minnesota; WJ Rietveld, Leiden University Dept of Path Netherlands; ME Boon, Leiden Netherlands Cytology and Path Dept

Objectives: Cervical cancer screening programs uncover vastly more "premalignant" epithelial lesions than cancers. Most of these lesions resolve spontaneously. Mammalian reproductive biology as well as the biology of cancers arising in reproductive tissues are modulated seasonally. Careful consideration of the annual biologic rhythms is essential for effective cancer control as well as to prevent overdiagnosis and overtreatment.

Methods: We inspected the monthly frequencies (per thousand screening examinations) of HPV infection, mild, moderate and severe dysplasias and atypias, as well as carcinoma in situ, micro invasive carcinoma and frankly invasive cervical cancer, among 920,359 consecutive interpretable pap smears obtained by a single screening laboratory in Leaden, Holland during a continuous 16 year span from 1983 through 1998.

Results: Profound and similar circannual rhythmicity characterizes each of these cervical epithelial abnormalities. Circannual rhythms in sex hormone concentration, human sexual activity and conception frequency in Northern Europe co-vary with these August peaking annual rhythms in HPV, precancer and cervical cancer detection among Dutch women. Peri-equatorial conception frequency and cervical cancer detection frequency each peak in winter rather than summer.

Conclusions: These data imply that all of the biological steps in uterine cervical epithelial carcinogenesis wax and wane during the year with a pattern that is characteristic for the altitude and weather of a populationís residence. Similar circannual epidemiologic data are available for the frequency of the diagnosis of prostate, testicular and breast cancer. Careful consideration of the annual biologic rhythms is essential for effective cancer control as well as to prevent overdiagnosis and overtreatment.

Impact: The biological steps in uterine cervical epithelial carcinogenesis wax and wane during the year with a pattern that is characteristic for the altitude and weather of a populationís residence. Careful consideration of the annual biologic rhythms is essential for effective cancer control as well as to prevent overdiagnosis and overtreatment.