Spontaneous regression and over diagnosis of cancer detected by screening
Dear Sir
re Zahl et al
The original immune surveillance hypothesis of Macfarlane Burnet and Thomas[1] suggested that more cases of cancer developed and were rejected by spontaneous rejection than ever became clinically significant and this was a very important role of the immune system. In their paper (BMJ 2004 329 921) Zahl et al do not consider this as a possible explanation of their findings. Though they mention the increased recognition of prostate cancer produced by PSA screening, they do not mention there is a considerable literature showing that this excess is found in studies of the prostate at post mortem in 27% of 40 year old men dying of non-cancer causes[2] but that even then the incidence is far in excess of that found by screening. I have found no reference to such histological studies of breasts from women dying of other causes than cancer.
For cervix cancer the over diagnosis rate is even higher than either breast or prostate cancer[3] and presumably reflects the direct access to the cervix producing a higher detection rate of latent cancer. Cervix cancer also provides evidence that spontaneous regression is a significant factor effecting 30-50% of early invasive cancers[4]. In one
study a surprising 100% regression occurred after 6 months use of condoms[5], suggesting that these latent cancers may be particularly susceptible to simpler treatments than we currently use and study of this further might reduce the excessive morbidity of present day screening programmes. It might also make screening more cost effective in less well off countries that cannot afford them[6].
References
1. Burnet FM. The concept of immunological surveillance. Progress in Experimental Tumor Research. 1970;13:1-27.
2. Sakr WA, Haas GP, Cassin BF, Pontes JE, Crissman JD. The frequency of carcinoma and intraepithelial neoplasia of the prostate in young male patients.[see comment]. Journal of Urology. 1993;150(2 Pt 1):379-85.
3. Raffle AE, Mackenzie E. Management of cervical dyokariosis: no early answer. Br Med J 1994;309:270.
4. Nobbenhuis MA, Helmerhorst TJ, van den Brule AJ, Rozendaal L, Voorhorst FJ, Bezemer PD, et al. Cytological regression and clearance of high-risk human papillomavirus in women with an abnormal cervical smear. Lancet. 2001;358(9295):1782-3.
5. Richardson AC, Lyon JB. The effect of condom use in squamous cell cervical intra-epithelial neoplasia. Am J Obstet Gynaecol 1981;140(8):909-913.
6. Bhatla N, Mukhopadhyay A, Joshi S, Kumar A, Kriplani A, Pandey RM, et al. Visual inspection for cervical cancer Screening: Evaluation by doctor versus paramedical worker. Indian Journal of Cancer 2004;41(1):32-6.
Competing interests:
None declared
Competing interests:
No competing interests
21 April 2004
R. Tim D. Oliver
Sir Maxwell Joseph Professor in Medical Oncology
St Barts & The London School of Medicine, London EC1A 7BE
Rapid Response:
Spontaneous regression and over diagnosis of cancer detected by screening
Dear Sir
re Zahl et al
The original immune surveillance hypothesis of Macfarlane Burnet and Thomas[1] suggested that more cases of cancer developed and were rejected by spontaneous rejection than ever became clinically significant and this was a very important role of the immune system. In their paper (BMJ 2004 329 921) Zahl et al do not consider this as a possible explanation of their findings. Though they mention the increased recognition of prostate cancer produced by PSA screening, they do not mention there is a considerable literature showing that this excess is found in studies of the prostate at post mortem in 27% of 40 year old men dying of non-cancer causes[2] but that even then the incidence is far in excess of that found by screening. I have found no reference to such histological studies of breasts from women dying of other causes than cancer.
For cervix cancer the over diagnosis rate is even higher than either breast or prostate cancer[3] and presumably reflects the direct access to the cervix producing a higher detection rate of latent cancer. Cervix cancer also provides evidence that spontaneous regression is a significant factor effecting 30-50% of early invasive cancers[4]. In one
study a surprising 100% regression occurred after 6 months use of condoms[5], suggesting that these latent cancers may be particularly susceptible to simpler treatments than we currently use and study of this further might reduce the excessive morbidity of present day screening programmes. It might also make screening more cost effective in less well off countries that cannot afford them[6].
References
1. Burnet FM. The concept of immunological surveillance. Progress in Experimental Tumor Research. 1970;13:1-27.
2. Sakr WA, Haas GP, Cassin BF, Pontes JE, Crissman JD. The frequency of carcinoma and intraepithelial neoplasia of the prostate in young male patients.[see comment]. Journal of Urology. 1993;150(2 Pt 1):379-85.
3. Raffle AE, Mackenzie E. Management of cervical dyokariosis: no early answer. Br Med J 1994;309:270.
4. Nobbenhuis MA, Helmerhorst TJ, van den Brule AJ, Rozendaal L, Voorhorst FJ, Bezemer PD, et al. Cytological regression and clearance of high-risk human papillomavirus in women with an abnormal cervical smear. Lancet. 2001;358(9295):1782-3.
5. Richardson AC, Lyon JB. The effect of condom use in squamous cell cervical intra-epithelial neoplasia. Am J Obstet Gynaecol 1981;140(8):909-913.
6. Bhatla N, Mukhopadhyay A, Joshi S, Kumar A, Kriplani A, Pandey RM, et al. Visual inspection for cervical cancer Screening: Evaluation by doctor versus paramedical worker. Indian Journal of Cancer 2004;41(1):32-6.
Competing interests:
None declared
Competing interests: No competing interests