Screening and cervical cancer cure: population based cohort study
BMJ 2012; 344 doi: https://doi.org/10.1136/bmj.e900 (Published 01 March 2012) Cite this as: BMJ 2012;344:e900All rapid responses
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This is a very interesting paper epidemiologically and statistically. But researchers/authors are simply reieterating the established fact that early diagnosis before the spread of cervical cancer (and/or before it is symptomatic) will prolong the life span, a fact which we study in gynaecological books e.g. "Gynaecology by Ten Teachers" (18th edition, p 131).
Competing interests: No competing interests
Andrae and co-workers (1) demonstrated that cytological screening was effective in improving cervical cancer cure, and that regular repetition of Pap smear significantly increased the benefit.
The question here is what would have happened if HPV testing were available and used instead of or together with cytology. In fact, a single HPV test has been shown to be more sensitive than a single Pap smear for the detection of pre-cancerous lesions.(2) However, test performance of cytology greatly improves after repeated testing during time. Repeat screening at 3-year intervals would prevent about 90% of cervical cancers. Annual testing with cytology between the ages of 20 and 29 years reduces the risk of missing a lesion to less than 0,2%. If a woman has an additional 10 tests between the ages of 30 and 50 years, the risk of a missed lesion falls to less than 0,001%.(3) Moreover, the combination of HPV testing and cytology (co-testing) was not demonstrated to detect high-grade cervical intraepithelial neoplasia more accurately than cytology alone.(2) Indeed, a reduction in mortality from implementation of HPV testing and combination methods has not yet been definitively demonstrated.
The average specificity of the Pap test is 95%, whereas the specificity of HPV testing has been estimated to be 75-80%.(3) With the introduction of HPV testing the number of women who result positive are doubled with respect to cytology. Given that spontaneous resolution of HPV infection is common, and that HPV-associated lesions have a negligible potential to develop into cancer, more positive cases may be identified, but the impact on cancer morbidity and mortality may reveal marginal.(3) In addition, most of the 50% of women with a normal Pap smear would ask for referral for colposcopy, and then for repeated HPV testing during the follow-up period,(4) thus raising costs and increasing morbidity associated with unwarranted treatments.
Improving sensitivity should be a public health-policy target if most cervical cancers develop from lesions missed by current testing. Conversely, more than 50% of cervical cancers results from inadequacies in screening. Data from Andrae et al. study(1) confirm that the largest gain in reducing the burden of cervical cancer deaths is best achieved by increasing screening rates among women who have never or rarely been screened. In this regard, increasing both, test sensitivity and cost, might reveal counterproductive. In fact, an increase in the cost of screening may lead to reduced acceptability of the program by a large number of women from lower socio-economic classes. Reducing adherence in indigent women, who are much more numerous and at higher risk of cervical cancer than wealthy ones, may undermine any screening strategy.
The implementation of HPV testing in cervical cancer prevention programs in developed countries, where the infrastructure for cytological diagnosis, triage by means of colposcopy with biopsy, and treatment of high-grade precursors are all available, would undoubtedly amplify the problem of overdiagnosis and overtreatment.(3) Only time will clarify whether embracing this modification in screening will translate also in higher cure proportions compared with those offered by cytology alone.(1)
References
1. Andrae B, Andersson TML, Lambert PC, Kemetli L, Silfverdal L, Strander B, et al. Screening and cervical cancer cure: population based cohort study. BMJ 2012;344:e900.
2. Whitlock EP, Vesco KK, Eder M, Lin JS, Senger CA, Burda BU. Liquid-based cytology and human papillomavirus testing to screen for cervical cancer: A systematic review for the U.S. Preventive Services Task Force. Ann Int Med 2011;155:687-697.
3. Massad LS. Assessing new technologies for cervical cancer screening: beyond sensitivity. J Low Genit Tract Dis 2008;12:311-5.
4. Frederiksen ME, Lynge E, Rebolj M. What women want. Women's preferences for the management of low-grade abnormal cervical screening tests: a systematic review. BJOG 2012;119:7-19.
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The article, Screening and cervical cancer cure: population based cohort study, is extremely valuable. It demonstrates that screening is associated with improved cure of cervical cancer. The publication also demonstrates that women whose cervical cancer is diagnosed by smear test have a better prognosis then when cervical cancer is detected on the basis of symptoms.
In a recent study, Sadler et al. Lifetime sexual assault and cervical cytologic abnormalities among military women. J Womens Health 2011;20:1693–1701, the authors state that sexual assault is a significant risk factor for abnormal cervical cytology.
In addition, multiple publications, Kelly et al, More than militarysexual trauma: Interpersonal violence, PTSD, and mental health in women veterans. Res Nurs Health 2011;34:457–467, have reported the incidence of military sexual trauma among women veterans to be as high as 40%. This increases their risk for abnormal cervical cytology.
The article by Bengt Andrae, et. al, clearly demonstrates that women veterans, many of whom have experienced sexual assault, need to be vigilant in having timely smears since screening is associated with improved cure of cervical cancer.
VA Healthcare has increased services for women veterans as their number has grown. Women’s health Clinics have been instituted throughout the United States and are providing preventive screening, including cervical smear tests. This vigilance in screening for abnormal cervical cytology is clearly imperative given the high incidence of military sexual trauma among women veterans
and the findings reported in the article, Lifetime Sexual Assault and Cervical Cytologic Abnormalities Among Military Women.
The publication by Bengt Andrae et al. is much appreciated as it underscores the importance of regular screening with cervical smears. Given the authors’ statement regarding the improved prognosis of women whose cervical cancer is detected through screening, it is clear that women veterans need regular testing to improve their chances of future good health. VA hopes that women veterans will come to the clinics for care. We are reaching out to this population and want them to know that we have improved services to meet their needs.
Competing interests: No competing interests
Exaggerating the benefits of organized cervical cytology screening is likely to be accepted by the mass media even if based on a study with weak methodology like a cohort study. This has happened in Sweden recently as a response to the article published in BMJ 2012;344:e900. The authors emphasized the positive effects of organized cervical cytology mass screening. They reported higher modelled cure rates in women with screen detected cervical cancer compared with those with symptomatic cancer.
Here are some critical points of view necessary in order to balance the debate.
One of the most important contributing factors for the better survival rates in screened individuals is the ”healthy voluteer bias". It has been shown that coverage rate in the organized Swedish mass screening program is around 70%. Therefore around 30% are not participating in the organized screening program. This is a considerably large group of women who might be at considerable higher risk than women attending screening. There could be an overrepresentation of women in lower social class or immigrant women in this category of women who are not attending screening. This is in contrast to what the authors mentioned in their discussion. But that the healthy volunteer bias might be of importance even for a Swedish population has been shown in a study from Sweden. Relative survival by social class was calculated from cases in the Swedish Cancer Registry. There was a significantly higher survival probability in women with invasive cervical cancer for ”white collar workers” compared with ”blue collar workers” (J Epidem Commun Health, 1987;41:204).
Therefore ”health volunteer bias” cannot be excluded as a factor which influences the modelled higher survival probability in screening detected cancer in the study published in the BMJ. Another important question is if survival modells can replace randomised controlled trials and compensate for lead time bias, I doubt it. Only randomised controlled trial can answer the question whether organised cervical cytology mass screening can reduce cervical cancer mortality and improve survival. Unfortunately those studies have never been performed. Never the less we should not exaggerate the benefits of an outdated screening test like cytology and use better screening tests in the future which are better evaluated than cervical cytology.
Competing interests: No competing interests
Re: Screening and cervical cancer cure: population based cohort study
Harmful excess is part of these programs in some countries. The Australian program has always been excessive and remains so, now more than a decade behind the evidence. A review has only just started, but I fear excess will remain.
Women are still being urged to have 2 yearly pap testing from 18-20 to age 70, serious over-screening.
If we compare our program to evidence based programs in the Netherlands and Finland we see there is no need to put women through frequent pap testing and send high numbers for excess biopsies and potentially harmful over-treatment.
The Finns have had a 6-7 pap test program since the 1960's, 5 yearly from age 30 to 60 and have the lowest rates of cervical cancer in the world and refer far fewer women, their program produces fewer false positives. The Dutch have the same program, but the Health Council of the Netherlands have recommended a move to a new program, 5 hrHPV primary triage tests offered at ages 30,35,40,50 and 60 and only the roughly 5% who are HPV positive and at risk will be offered a 5 yearly pap test. Those negative, the vast majority, will be offered the HPV primary triage program and there is also a long overdue self-test device, the Delphi Screener (already in use in Singapore, Malaysia, the Netherlands and elsewhere).
This program finally spares the vast majority of women who are not-at-risk (HPV negative) from a lifetime of unnecessary pap testing and removes the risk of over-treatment. It is also more likely to save lives by identifying the fairly small number actually at risk from cervix cancer, about 5% of women aged 30 or more. It will save money in the long run by removing most women from pap testing and over-treatment. This also means fewer women with damage to the cervix and premature babies, miscarriages, the need for c-sections etc
Of course, I fear excess will be built into any new program here....this is not in the interests of women. A program of 3 yearly liquid pap testing from 25 to 70 just means a lifetime of unnecessary pap testing and the risk of over-treatment for most women and offering pap testing AND HPV testing to all women just sends up costs, is unhelpful and leads to over-investigation. The HPV primary test should stand alone.
I firmly believe these programs should be controlled by independent groups that will focus on what's best for women, like the Nordic Cochrane Institute. I note the new Dutch program came about after doctors/experts were asked to provide their personal opinions, NOT as representatives of a professional body.
I think the only way to protect our health is to do our own research and make an informed decision about testing. Why would any HPV negative woman wish to endure a lifetime of unnecessary pap testing and accept a fairly high risk of over-treatment?
Competing interests: No competing interests