- Email: [email protected]
POSSIBLE PREVENTION OF BRONCHIAL CARCINOMA BY RECURRENT HERPES SIMPLEX
871 be noted: the be drawn, or imaginary trends detected, from single studies and from samples in which only small numbers of individuals fall into a specific group which may be of interest.
This is
perhaps the
most
interesting point
readiness with which false conclusions
University Department of Anæsthetics, Withington Hospital, Manchester M20 8LR.
to
can
TABLE I-HISTORY OF RECURRENT HERPES LABIALIS, SHINGLES, AND CHICKENPOX IN CASES OF BRONCHIAL CARCINOMA AND IN CONTROLS
CYNTHIA MCLAUGHLIN JAMES PARKHOUSE.
POSSIBLE PREVENTION OF BRONCHIAL CARCINOMA BY RECURRENT HERPES SIMPLEX
SIR,-Recent reportshave shown that the body’s defences are active against neoplastic cells, and much research is concerned with enhancing existing immune responses to tumour growth. In the prevention of neoplasia it seems that agents boosting immune responses may be important. Thus, the common viral infections of childhood and adolescence may produce immunity not only against the specific infecting agent but also against neoplastic change. This may explain why malignancy is most common at the extremes of life (i.e., before and after the period of life when viral infections are common). In adult life the main periodic active infections are associated with the herpes group of viruses, particularly with herpes-simplex virus. Therefore, we have tried to compare the proportion of patients with bronchial carcinoma who had had recurrent herpes labialis-the commonest clinical manifestation of recurrent infection with herpes-simplex virus-and the proportion in controls without carcinoma. Also, an attempt was made to ascertain the numbers of cases and controls who had had infections with varicella-zoster virus, another herpes-group virus which may become reactivated. The series comprised 100 patients (81 males and 19 females) with bronchial carcinoma admitted to the chest unit, Ruchill Hospital, in 1972-73; 85 were aged 50-80 years. Controls comprised patients in the chest unit or from the chest clinic, without bronchial carcinoma at the time of examination; the majority had chronic bronchitis or cardio-pulmonary disease; each control was of the same age (± 5 years) as the corresponding carcinoma case. All cases and controls were interviewed by the same investigator (W. F. T.), who used the following question " Do you know what a cold procedure throughout-namely, sore is? " When the interviewer was satisfied that the patient understood that a cold sore meant blisters on the lips sometimes associated with " colds ", fever, strong sunlight, or strong winds, the patient was asked if he suffered from cold sores. If the answer was in the affirmative he was asked if the attacks usually occurred more or less often than once yearly. Also, inquiry was made about previous attacks of shingles (herpes zoster) and chickenpox (varicella) and patient’s age at time of each illness. If he did not know or could not remember, this was recorded as " unknown ". Finally, a smoker was asked for how many years he had smoked and an estimate was made of the average number of cigarettes smoked daily. Smokers were grouped as " heavy " if they smoked 15 or more cigarettes per day, as " light " if less than 15 daily, and as " ex-smokers " if they had stopped smoking more than a year previously.
A
history of recurrent herpes labialis was obtained in significantly fewer carcinoma patients than controls (table l): 21 of 100 cases compared with 42 of 100 controls (x2, 0-01 >p> 0-001). Recurrences were more frequent than once yearly in 5 of the 21 cases and 9 of the 42 controls. The range of serum c.F. antibody titres to herpes simplex type 1 was similar in cases and controls; there was no apparent correlation between antibody titres and clinical recurrences of herpes simplex. Although a history of shingles was also obtained in fewer cases than controls (8 cases compared with 12 controls) the difference is not statistically significant (x2, 0-50 >p> 0-30). The number 1.
Klein, G. Clin. Immun. 1972, 1, 219.
a history of chickenpox was similar for cases and controls; but, since chickenpox is mainly a childhood infection, many of the patients and controls could not remember if they had had this illness; thus the answers for chickenpox were less reliable than for shingles and herpes
giving
labialis. There were more smokers among the cases than the controls (table 11) (92 cases compared with 84 controls); the difference is not statistically significant, but would probably have been so if the controls had been healthy individuals, since it is certain that smoking was an aetiological factor in the illnesses suffered by many of the controls-namely, chronic bronchitis and cardio-pulmonary disease. Our results suggest that recurrent herpes-simplex infections may provide specific or non-specific immunological protection against bronchial carcinoma. Concerning non-specific immunological protection, it is now recognised that the incidence of cancer is increased by administration of immunosuppressive drugs, by thymectomy, or in diseases that involve a deficiency of cellmediated immunity.2 Conversely, it seems possible that a recurrent herpes-simplex infection might provide a nonspecific stimulus to immunological surveillance, particularly to cell-mediated immunity. Specific viral-related protection might play a part in our findings if the cause of some cases of bronchial carcinoma were associated with herpes-simplex virus infection or with a virus antigenically related to herpes simplex. Induction of tumours in chicks by the oncogenic herpes virus of Marek’s disease can be prevented by an antigenically related turkey herpes virus which is non-pathogenic for chickens.33 Although we failed to demonstrate any difference between herpessimplex humoral antibody in cases and controls, it seems possible that specific immunological surveillance may operate through cell-mediated immunity or, as has been shown in Marek’s disease, against the virus-induced malignant cell rather than against the virus itself. In cellcultures transformed-i.e., rendered neoplastic-by infection with irradiated herpes-simplex virus a cytoplasmic antigen specific for herpes simplex has been detected by indirect immunofluorescence.44 It might therefore be worth while testing sera from patients with bronchial carcinoma and from control cases for antibodies against cells transformed by herpes simplex; this was not possible in the nresent studv. Regional Virus Laboratory and Chest Unit, CONSTANCE A. C. ROSS Ruchill Hospital, W. F. TYRRELL. Glasgow, G20 9NB. Doll, R., Kinlen, L. Br. med. J. 1970, iv, 420. Payne, L. N. in Symposium on Oncogenesis and Herpes-type Viruses; p. 21. New York, 1972. 4. Duff, R., Rapp, F. Perspect. Virol. 1973, 8, 189.
2. 3.
This is
perhaps the
most
interesting point
readiness with which false conclusions
University Department of Anæsthetics, Withington Hospital, Manchester M20 8LR.
to
can
TABLE I-HISTORY OF RECURRENT HERPES LABIALIS, SHINGLES, AND CHICKENPOX IN CASES OF BRONCHIAL CARCINOMA AND IN CONTROLS
CYNTHIA MCLAUGHLIN JAMES PARKHOUSE.
POSSIBLE PREVENTION OF BRONCHIAL CARCINOMA BY RECURRENT HERPES SIMPLEX
SIR,-Recent reportshave shown that the body’s defences are active against neoplastic cells, and much research is concerned with enhancing existing immune responses to tumour growth. In the prevention of neoplasia it seems that agents boosting immune responses may be important. Thus, the common viral infections of childhood and adolescence may produce immunity not only against the specific infecting agent but also against neoplastic change. This may explain why malignancy is most common at the extremes of life (i.e., before and after the period of life when viral infections are common). In adult life the main periodic active infections are associated with the herpes group of viruses, particularly with herpes-simplex virus. Therefore, we have tried to compare the proportion of patients with bronchial carcinoma who had had recurrent herpes labialis-the commonest clinical manifestation of recurrent infection with herpes-simplex virus-and the proportion in controls without carcinoma. Also, an attempt was made to ascertain the numbers of cases and controls who had had infections with varicella-zoster virus, another herpes-group virus which may become reactivated. The series comprised 100 patients (81 males and 19 females) with bronchial carcinoma admitted to the chest unit, Ruchill Hospital, in 1972-73; 85 were aged 50-80 years. Controls comprised patients in the chest unit or from the chest clinic, without bronchial carcinoma at the time of examination; the majority had chronic bronchitis or cardio-pulmonary disease; each control was of the same age (± 5 years) as the corresponding carcinoma case. All cases and controls were interviewed by the same investigator (W. F. T.), who used the following question " Do you know what a cold procedure throughout-namely, sore is? " When the interviewer was satisfied that the patient understood that a cold sore meant blisters on the lips sometimes associated with " colds ", fever, strong sunlight, or strong winds, the patient was asked if he suffered from cold sores. If the answer was in the affirmative he was asked if the attacks usually occurred more or less often than once yearly. Also, inquiry was made about previous attacks of shingles (herpes zoster) and chickenpox (varicella) and patient’s age at time of each illness. If he did not know or could not remember, this was recorded as " unknown ". Finally, a smoker was asked for how many years he had smoked and an estimate was made of the average number of cigarettes smoked daily. Smokers were grouped as " heavy " if they smoked 15 or more cigarettes per day, as " light " if less than 15 daily, and as " ex-smokers " if they had stopped smoking more than a year previously.
A
history of recurrent herpes labialis was obtained in significantly fewer carcinoma patients than controls (table l): 21 of 100 cases compared with 42 of 100 controls (x2, 0-01 >p> 0-001). Recurrences were more frequent than once yearly in 5 of the 21 cases and 9 of the 42 controls. The range of serum c.F. antibody titres to herpes simplex type 1 was similar in cases and controls; there was no apparent correlation between antibody titres and clinical recurrences of herpes simplex. Although a history of shingles was also obtained in fewer cases than controls (8 cases compared with 12 controls) the difference is not statistically significant (x2, 0-50 >p> 0-30). The number 1.
Klein, G. Clin. Immun. 1972, 1, 219.
a history of chickenpox was similar for cases and controls; but, since chickenpox is mainly a childhood infection, many of the patients and controls could not remember if they had had this illness; thus the answers for chickenpox were less reliable than for shingles and herpes
giving
labialis. There were more smokers among the cases than the controls (table 11) (92 cases compared with 84 controls); the difference is not statistically significant, but would probably have been so if the controls had been healthy individuals, since it is certain that smoking was an aetiological factor in the illnesses suffered by many of the controls-namely, chronic bronchitis and cardio-pulmonary disease. Our results suggest that recurrent herpes-simplex infections may provide specific or non-specific immunological protection against bronchial carcinoma. Concerning non-specific immunological protection, it is now recognised that the incidence of cancer is increased by administration of immunosuppressive drugs, by thymectomy, or in diseases that involve a deficiency of cellmediated immunity.2 Conversely, it seems possible that a recurrent herpes-simplex infection might provide a nonspecific stimulus to immunological surveillance, particularly to cell-mediated immunity. Specific viral-related protection might play a part in our findings if the cause of some cases of bronchial carcinoma were associated with herpes-simplex virus infection or with a virus antigenically related to herpes simplex. Induction of tumours in chicks by the oncogenic herpes virus of Marek’s disease can be prevented by an antigenically related turkey herpes virus which is non-pathogenic for chickens.33 Although we failed to demonstrate any difference between herpessimplex humoral antibody in cases and controls, it seems possible that specific immunological surveillance may operate through cell-mediated immunity or, as has been shown in Marek’s disease, against the virus-induced malignant cell rather than against the virus itself. In cellcultures transformed-i.e., rendered neoplastic-by infection with irradiated herpes-simplex virus a cytoplasmic antigen specific for herpes simplex has been detected by indirect immunofluorescence.44 It might therefore be worth while testing sera from patients with bronchial carcinoma and from control cases for antibodies against cells transformed by herpes simplex; this was not possible in the nresent studv. Regional Virus Laboratory and Chest Unit, CONSTANCE A. C. ROSS Ruchill Hospital, W. F. TYRRELL. Glasgow, G20 9NB. Doll, R., Kinlen, L. Br. med. J. 1970, iv, 420. Payne, L. N. in Symposium on Oncogenesis and Herpes-type Viruses; p. 21. New York, 1972. 4. Duff, R., Rapp, F. Perspect. Virol. 1973, 8, 189.
2. 3.