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Cervical screening according to age and HPV status, UK and Costa Rica.

Strong evidence is now available that testing for human papillomavirus (HPV) infection is more sensitive than cytology in detecting high-grade cervical intraepithelial neoplasia, but less specific. HPV testing might soon be accepted as an alternative to routine cytology, but it is important first to find ways of improving its low predictive value for high-grade lesions.

One of two linked articles shows that the risk of developing high grade lesions in the next three to five years is much higher in women with HPV infection that has persisted for at least one year than in those in whom the infection cleared. The population-based cohort study included 2,282 sexually active women from Guanacaste, Costa Rica, enrolled in 1993-1994. Researchers examined the utility of measuring viral persistence over 9-21 months and the risk of pre-cancer and cancer over the subsequent years, and what differentiates women at lesser and greater risk. Women who tested positive twice for a carcinogenic HPV had a three-year, cumulative incidence of high-grade lesions of 17%, significantly higher than the risk in women who tested negative at either or both times. Persistent positivity for any high-risk HPV type entailed almost the same risk as persistent positivity for the same type, particularly for women aged over 30. However, persistent infection by HPV types 16 and possibly 18 predicts a much higher future risk of high-grade lesions than for other types. Such risk stratification is important for clinical management. Repeat testing might divide the population into low and high risk for incipient lesions, and detection of HPV 16 and 18 might be particularly useful to identify women at high risk. It is less clear whether there is clinical utility in detecting persistence of carcinogenic HPV genotype other than 16 and 18. (1)

Effectiveness of cytological screening in preventing cancers is limited below the age of 25, and screening is fully effective only from age 35. A population-based case-control study selected 4,012 women aged 20-69 with invasive cancer at participating centres in the UK and two controls per case matched on age and area of residence. The efficacy of screening decreased with decreasing age, even within the age range 20-34. There is no evidence that screening women aged 20-24 reduces the incidence of cervical cancer under the age of 30. The same pattern was seen for microinvasive and fully invasive cancers. Participation in a screening programme by a woman aged 35-64 reduces her risk of cervical cancer over the next five years by 60-80% and her risk of advanced cervical cancer by 90%. Screening was particularly effective for advanced staged cancers. (2)

The question of whether to screen women aged 20-24 will decrease in importance as the cohort of women vaccinated against HPV types 16 and 18 reach their 20s, and cytological screening will become unjustifiable. At these younger ages, the main challenge is to find any progressive lesions and avoid treating the remaining lesions. Thus, looking at persistence of HPV infection could help identify those at low risk and limit excessive referral for colposcopy. (3)

There is insufficient evidence on whether screening should be extended beyond 6065 years of age. With modern technology screening invitations could be tailored to the individual with information on HPV tests, HPV vaccination, previous precursor lesions and smear test results being incorporated into algorithms, so that screening over 60 would only be applied to those who would benefit most from it. (4)

(1.) Castle PE, Rodriguez AC, Burk RD, et al. Short term persistence of human papillomavirus and risk of cervical precancer and cancer: population based cohort study. BMJ 2009;339:b2569.

(2.) Sasieni P, Castanon A, Cuzick J. Effectiveness of cervical screening with age: population based case-control study of prospectively recorded data. BMJ 2009;339:b2968.

(3.) Ronco G, Arbyn M, Segnan N. Cervical screening according to age and HPV status. BMJ 2009 ;339:b3005.

(4.) Strander B. At what age should cervical screening stop? BMJ 2009;338:b809.
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Title Annotation:ROUND UP: Research
Publication:Reproductive Health Matters
Geographic Code:2COST
Date:May 1, 2009
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