The future of cervical screening is being carefully scrutinised. There is no doubt that cytology is one of the most valuable of all screening modalities, being able to detect pre-cancerous lesions while they are amenable to curative procedures that prevent more serious disease.
The profession and the public are analysing the role of all population screening strategies with the harms being objectively assessed as well as the benefits. There is a temptation to become caught up in the preventative fervour of prophylactic screening without looking at the downside implicit in all programmes. These negative aspects are derived from an over-reaction to minor deviations or difficult-to-interpret results, as well as the psychological and emotional fall-out generated by false positives. There is a spectrum of under-recognised harm from a pre-occupation with abnormal labels, through to the financial interests of business to grow the screening industry.
Health professionals exhort their patients to prevent disease and it is easy to slip into the simplistic mantra of early detection being the equivalent of prevention. Screening is no more preventative than insuring your home is preventative of its burning down. While reminding ourselves of the differences between screening and prevention, it is as well to remember the fundamentals of an effective screening test which should have the following characteristics (Clark Cancer Control 1995;2:485-92):
1. The disease sought should be an important health problem
2. A presymptomatic stage of the disease should exist
3. The natural history of the disease should be well understood
4. There should be an acceptable screening test available
5. Screening tests should be acceptable to the population being tested
6. Outcomes after presymptom diagnosis and treatment should be better than those after symptoms
7. Reduced morbidity/mortality should outweigh harms from false-positive tests
8. Benefits of the test should be achieved at acceptable risk
So does population based cervical cytology measure up to these ideals?
The massive reduction in deaths from cervical cancer in countries where programmes have been introduced does not preclude its re-evaluation as every intervention must be reconsidered in the present economic melt down. Fortunately cytology does hold up cost-effectively in developed countries like the United States where the burden of the disease has decreased by 75% but there are other strategies which need to be considered in developing countries where the costs of clinics, laboratories administration and personnel are prohibitive.
The role of HPV DNA testing in screening is starting to emerge. At present HPV tests are used to triage women with equivocal cytology who may or may not need colposcopy.
The next focus for HPV tests has been in women over the age of 30 years. These women are past the stage of self-limiting infections, and if they are HPV negative with normal cytology then they may constitute a group in whom fewer smears are necessary. Less frequent screening carries large financial implications.
Castle et al (Obstet Gynecol 2009;113:595-600) looked at the number of women who had oncogenic HPV positive tests in the general population of California and evaluated their cytology at the same time. Those between 30 and 34 years had 10% HPV oncogenic positive results but this dropped to around 5% in women older than 40 years. In the entire population the HPV positive rate was lower than anticipated thus not realising epidemiologists' fears of a sharply increased need for further investigation if widespread HPV screening is introduced. Conversely women with negative HPV tests plus negative cytology had a very low risk of incipient precancer and their screening can safely be extended beyond 3 years.
In some practices an “annual smear” has become traditional and women may be reluctant to give up their routine check-ups for fear of failing to detecting early disease. Cotesting with both cytology and HPV DNA may resolve this issue.
When to stop screening is an unsettled matter. There is no point in cytological screening in women who have had their cervix removed by hysterectomy for benign indications. Vault smears are not justified, but for older women with a cervix, when should screening end? Recommendations vary from country to country with 65 or 70 being the most frequently advised age on both sides of the Atlantic but this is in low-risk women who are asymptomatic. Certainly the latest data from Denmark (Rebolj et al (BMJ 2009; 338:b1354) indicates that negative smears in women in their fifties have the same predictive value as women in their thirties suggesting continued vigilance is a good idea.
Finally, Strander (BMJ 2009:338:b809) believes the story will unfold as the technology improves with computer generated risk factors guiding the frequency and duration of screening. Surely algorithms can be devised which include lifestyle considerations plus previous cytology and HPV results which would streamline services, save unnecessary retesting as well as indicating when to stop screening?
10 July, 2009
23 April, 2009
Breast Cancer Screening
The national routine breast screening programme in the UK has doubled the number of women screened in the last 10 years and it is now approaching 2 million per year. This is due to more women availing themselves of the service and an extension of the previously restricted age offer to 50 - 65 year-olds by a further 5 years. The latest data reveal twice the number of cases detected compared with a decade ago, with most being invasive and half being less that 1.5cm in size which are not detectable by hand (Mayor BMJ 2009;338:315).
The claim is made that the programme is serving an “increasing number of women's lives” but this is not a universally accepted point of view.
A spirited rebuttal to unconditional screening programmes is made by Gotzsche et al (BMJ 2009;338:446-8) in which the point is made that mammography has a downside - cost, discomfort, false-positive findings and over-treatment. The authors castigate programmes whose information leaflets fail to mention the harmful effects of screening and over-emphasize the benefits. They argue that choices about screening can only be made by healthy women if the cons as well as the pros are presented. They looked at 31 leaflets from publicly-funded programmes and found them all to be biased so they have produced their own evidence-based contribution (see www.bmj.com).
Women should not be coerced or made to feel guilty if they choose not to undergo screening - informed choice implies unbiased information.
While on the topic of screening for women, the latest figures of cervical screening in the UK are quoted by Kmietowicz (BMJ 2009;338:497). Since the national programme was introduced 30 years ago, the number of diagnoses of cervical cancer have halved. The disease has dropped from the 6th to the 13th most common cancer in women and mortality rates have plummeted. The only negative data show fewer young women are taking up screening invitations but, as a group, those under the age of 35 remain vulnerable.
The claim is made that the programme is serving an “increasing number of women's lives” but this is not a universally accepted point of view.
A spirited rebuttal to unconditional screening programmes is made by Gotzsche et al (BMJ 2009;338:446-8) in which the point is made that mammography has a downside - cost, discomfort, false-positive findings and over-treatment. The authors castigate programmes whose information leaflets fail to mention the harmful effects of screening and over-emphasize the benefits. They argue that choices about screening can only be made by healthy women if the cons as well as the pros are presented. They looked at 31 leaflets from publicly-funded programmes and found them all to be biased so they have produced their own evidence-based contribution (see www.bmj.com).
Women should not be coerced or made to feel guilty if they choose not to undergo screening - informed choice implies unbiased information.
While on the topic of screening for women, the latest figures of cervical screening in the UK are quoted by Kmietowicz (BMJ 2009;338:497). Since the national programme was introduced 30 years ago, the number of diagnoses of cervical cancer have halved. The disease has dropped from the 6th to the 13th most common cancer in women and mortality rates have plummeted. The only negative data show fewer young women are taking up screening invitations but, as a group, those under the age of 35 remain vulnerable.
11 March, 2009
Antioxidants and cancer prevention
Antioxidants are the hope of the healthy. Millions of people take supplements, usually vitamins or antioxidants, in the hope that these extras will prevent chronic conditions. The supplement industry is vast but many of the popular products so eagerly ingested lack scientific evidence of benefit.
The latest casualties are selenium and vitamin E for the prevention of cancer in men. In the largest randomised controlled trial ever undertaken, comprising over 35 000 people, these substances were no more effective than placebo in reducing the rates of prostate or any other cancers in middle-aged and elderly men. The trial was supposed to last 12 years but was stopped half-way when an interim audit shown no effect of each agent or a combination (Lippman et al JAMA 2009;301:39-51).
In a second smaller trial of 15 000 male doctors - also middle-aged - vitamins E and C were pitted against placebo and, again, after 8 years there was no decreased risk of any cancer found (Gazanio et al pp 52-62).
It seems clear that healthy men and women do not lower their chances of developing cancer by taking vitamins C, E or selenium. Half of all American adults take supplements. Will these definitive studies change their habits?
At the other end of the age spectrum, other additives have also not been faring very well. Theoretically, giving preterm infants high doses of polyunsaturated fatty acids in their diets could assist brain structure and function. Babies born before 33 completed weeks of gestation are at risk of developmental and behavioural problems, but it is unclear whether standard or high dose fatty acids in their early feeds will make any difference to long-term outcomes.
Makrides et al (JAMA 2009;301:175-82) supplemented the diet of the mothers whose expressed breast milk formed the bulk of the infant's nutrition. The intervention group took capsules containing tuna oil while the controls had a standard diet, resulting in the babies receiving either high or low doses of docosahexanoic acid (DHA) from birth to the date when they would have reached term in utero. Examining both groups at 18 months there was no difference in the neuro-developmental outcome between those receiving the DHA supplementation or not. However, the girls did better than the boys which may lead to even higher dose trials.
The latest casualties are selenium and vitamin E for the prevention of cancer in men. In the largest randomised controlled trial ever undertaken, comprising over 35 000 people, these substances were no more effective than placebo in reducing the rates of prostate or any other cancers in middle-aged and elderly men. The trial was supposed to last 12 years but was stopped half-way when an interim audit shown no effect of each agent or a combination (Lippman et al JAMA 2009;301:39-51).
In a second smaller trial of 15 000 male doctors - also middle-aged - vitamins E and C were pitted against placebo and, again, after 8 years there was no decreased risk of any cancer found (Gazanio et al pp 52-62).
It seems clear that healthy men and women do not lower their chances of developing cancer by taking vitamins C, E or selenium. Half of all American adults take supplements. Will these definitive studies change their habits?
At the other end of the age spectrum, other additives have also not been faring very well. Theoretically, giving preterm infants high doses of polyunsaturated fatty acids in their diets could assist brain structure and function. Babies born before 33 completed weeks of gestation are at risk of developmental and behavioural problems, but it is unclear whether standard or high dose fatty acids in their early feeds will make any difference to long-term outcomes.
Makrides et al (JAMA 2009;301:175-82) supplemented the diet of the mothers whose expressed breast milk formed the bulk of the infant's nutrition. The intervention group took capsules containing tuna oil while the controls had a standard diet, resulting in the babies receiving either high or low doses of docosahexanoic acid (DHA) from birth to the date when they would have reached term in utero. Examining both groups at 18 months there was no difference in the neuro-developmental outcome between those receiving the DHA supplementation or not. However, the girls did better than the boys which may lead to even higher dose trials.
26 January, 2009
Miscarriage and the next pregnancy
Women who miscarry their first pregnancy are naturally distressed, but what reassurance about the next pregnancy is appropriate? If she conceives again and the pregnancy continues to viability, is she at increased obstetric risk, or not?
Battacharya et al (BJOG 2008;115:1623-9) followed up a large group of women who experienced a spontaneous early pregnancy loss and compared them to women whose first pregnancy reached viability and to women having their second pregnancy after a first normal outcome.
Unsurprisingly, the lowest risk was found in the group who had an initial uncomplicated pregnancy, followed by primigravidas, then those who had experienced a miscarriage. One miscarriage was associated with more obstetric complications, such as threatened miscarriage, pre-eclampsia, induced labour, instrumental delivery, preterm delivery and a low birth-weight infant, compared with those who had a successful pregnancy. Compared with primigravidas, they were more at risk of threatened miscarriage, induction, preterm labour and post-partum haemorrhage.
It is not clear whether this expectation of behaving like a “virtual primigravida” is related to the way the miscarriage was dealt with - by surgical evacuation, expectant management or medical evacuation. It is equally unclear whether waiting before trying for a replacement pregnancy will give a woman a better chance of a successful outcome. Steer suggests that an interval of 18 months may improve her chances (Editor's Choice BJOG Dec 2008).
Battacharya et al (BJOG 2008;115:1623-9) followed up a large group of women who experienced a spontaneous early pregnancy loss and compared them to women whose first pregnancy reached viability and to women having their second pregnancy after a first normal outcome.
Unsurprisingly, the lowest risk was found in the group who had an initial uncomplicated pregnancy, followed by primigravidas, then those who had experienced a miscarriage. One miscarriage was associated with more obstetric complications, such as threatened miscarriage, pre-eclampsia, induced labour, instrumental delivery, preterm delivery and a low birth-weight infant, compared with those who had a successful pregnancy. Compared with primigravidas, they were more at risk of threatened miscarriage, induction, preterm labour and post-partum haemorrhage.
It is not clear whether this expectation of behaving like a “virtual primigravida” is related to the way the miscarriage was dealt with - by surgical evacuation, expectant management or medical evacuation. It is equally unclear whether waiting before trying for a replacement pregnancy will give a woman a better chance of a successful outcome. Steer suggests that an interval of 18 months may improve her chances (Editor's Choice BJOG Dec 2008).
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