important that these patients be formally recalled at regular 3-year intervals. Extending the screening interval carries a definite risk that women may forget to return every 3 years. Therefore, the recall system should be operated in each province by means of computerized provincial registries as are recommended in the report. In 1971, almost 2.5 million women had Pap tests in Canada (unpublished data) and the numbers are undoubtedly higher now, so that the logistics of followup will require this approach, already adopted by some provinces. The report recommends that health authorities should support the development of cytologic screening programs designed to detect the precursors of invasive cancer of the cervix, and one recommendation is that, to function efficiently, a laboratory should process at least 25 000 gynecologic smears per annum. While this may be true from an economic viewpoint, the pathologist in many general hospital laboratories in Canada is required to provide a

nongynecologic cytology service for which a trained cytoscreener is required. Thus, many of these laboratories also process a number of gynecologic smears to allow for the employment of a full-time cytotechnologist, since it would be uneconomic to employ such a person for a relatively small, but still essential, number of nongynecologic specimens. From this point of view a minimum of 25 000 gynecologic smears per annum may not be practical in laboratories that fulfil both a service and a screening function. Cancer of the cervix is a preventable disease, but in practical terms it probably cannot be eliminated completely even in a highly developed country such as Canada. Undoubtedly we can achieve better coverage of the population at risk than has been accomplished up to this time. The recommendations in this report, if accepted by government, by the medical profession and by the public, and if acted upon as a unified whole, provide the basis for the establishment of comprehensive screen-

ing programs for carcinoma of the cervix in every province in Canada. These programs would be economically attractive, allowing more effective use of limited resources - money and skilled personnel. The beneficiaries would be the women who as yet have not responded to the publicity surrounding the screening programs. Each year invasive cancer of the cervix develops in many of them, and hence they represent a failure of our present system. G.H. ANDERSON, MB, BS, FRCP[C] Director Section of cytopathology Pathology Institute Halifax, NS

References 1. BOYES DA, KNOWELDEN 3, PHILLIPS Al: The evaluation of cancer control sneaaures. Dr I Cancer 28: 105, 1973 2. S.asoos Al: Population screening by the cervical smear. Nature 238: 135, 1972 3. WAKEFIELD J: Introduction to Seek Wisely to Prevent, London, HMSO, 1972 4. MACGREGOR JE: Evaluation of early detection of cancer of the cervix. Paper, UICS symposium, Sheffield, England, Sept 1972 5. D,.v.soi. RL: Professional and public education in the Manchester region, in Cancer ol the Uterine Cervix, EASSON EC (ed), Toronto, Saunders, 1973, p 121

Cervical cancer screening programs: a gynecologist.s viewpoint Diagnostic cytology for cancer of the cervix was introduced in 1943, when Papanicolaou and Traut published their now famous monograph on diagnosis of uterine cancer by the vaginal smear. It then took several years for the medical profession to appreciate the value of the technique and several more years to convince the public that a Pap test could detect cancer of the cervix in its earliest stage of development. As the Pap test became a routine examination by many doctors treating women, screening programs for the detection of cancer of the cervix developed. Screening for cancer of the cervix has a particularly important advantage over screening for many other malignant conditions: the procedure is based on the detection of precursors of the truly invasive condition, and these precursors may be treated before the invasive malignant disease develops. Over the past 20 years screening has revealed a large number of cases of preclinical disease that could only have been detected by cytologic means. Dysplasia of the cervix, carcinoma in situ and microinvasive cancer of the cervix are all "new" diseases that do not give rise to symptoms. All are limited in extent and can be treated before invasive disease develops. Despite the ability of screening programs to detect cervical cancer and

its precursors, many have questioned whether mass screening is of any real benefit - specifically, does it decrease the incidence of invasive squamous carcinoma and does it decrease the mortality from this disease? Not only do we need answers to these questions but, because screening programs are expensive, their efficiency must be assessed. The value of screening programs for cancer of the cervix has been examined in depth by the task force appointed by the Conference of Deputy Ministers of Health, and this extremely important report, now published in the Journal, contains the evidence to support recommendations made to health authorities and physicians for changing our present routines of mass screening for cervical cancer. Current knowledge, as reviewed in the report, suggests that there are groups of women at different degrees of risk for carcinoma of the cervix. It is imperative that we, as medical practitioners, familiarize ourselves with these groups so that we can identify those most at risk and ensure that they regularly take advantage of screening facilities. Women in the low-risk group should be discouraged from having Pap tests more frequently than once every 3 years. This is a distinct departure from the usual annual Pap test. Current evidence shows, however, that, pro-

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vided two initial smears are normal, the probability of a subsequent abnormality is less than 0.7/ 1OOO.. Instead of repeating a Pap test in this low-risk group we should turn our attention to those in the high-risk group who are not being screened at all. In this way Canadian screening programs for cervical cancer could become more efficient without any increase in resources. The aim of a screening program is to detect disease at a stage when treatment is likely to be most effective. In the past 20 years there has been much new information regarding precancerous lesions of the cervix such as dysplasia and carcinoma in situ. Of these lesions 75% will eventually progress to invasive carcinoma, the length of time for a severe dysplasia or a carcinoma in situ of the cervix to progress to invasive squamous carcinoma varying from 3 to 20 years.3 But there is no point in detecting a condition if it cannot then be treated. In patients with an abnormal Pap smear, a tissue diagnosis is essential before definitive therapy is undertaken. Colposcopy, a technique developed almost 50 years ago, is proving to be ideal for evaluating the condition of such patients. It defines accurately the most suspicious area of the cervix so that a directed biopsy can be taken and the diagnosis confirmed. The necessity for diagnostic conization

Sinequar. It works safely Indications The antidepressant and anxiolytic properties of Sinequan (doxepin) have been found to be of value in the drug treatment of: 1. Psychoneurotic patients with anxiety and I or depressive reactions; Anxiety neurosis associated with somatic disorders; Alcoholic patients with anxiety and/or depression. 2. Psychotic depression, including manicdepressive illness (depressed type) and involutional melancholia. Contraindications Sinequan is contraindicated in individuals who have shown hypersensitivity to the drug. It is not recommended for children under 12 years of age, since sufficient data on its use in this age group is not yet available. Because of its anticholinergic activity Sinequan should not be administered to patients with glaucoma or a tendency to urinary retention. Tricyclic agents are generally contraindicated in patients with a history of blood dyscrasias and severe liver disease. Sinequan should not be administered concomitantly with MAO inhibitors, since such a combination may cause a syndrome of intensive sympathetic stimulation. Drugs of this type should be discontinued at least two weeks before instituting therapy with Sinequan. Precautions and Warnings The safety of Sinequan in pregnancy has not been established and therefore it should be used in pregnant women only when, in the judgment of the physician, it is essential for the welfare of the patients. Since drowsiness may occur with the use of this drug, patients should be warned of the possibility of this occurring early in the course of treatment, and cautioned against driving a car or operating machinery. Combined use with other drugs acting on the central nervous system should be undertaken with due recognition of the possibility of potentiation. The response to alcohol may also be modified. As with other antidepressant agents, the possibility of activation of psychotic symptoms should be borne in mind. Appropriate supervision is required when treating depressed patients, and alternate forms of management should be considered in treating severely depressed patients because of the inherent suicidal risk. Tricyclic agents may lower the convulsive threshold and should therefore be used with caution in patients with convulsive disorders. Sinequan should be used with caution in patients with cardiovascular disorders. At doses of 300 mg I day or above, it may block the antihypertensive effect of guanethidine and related compounds. The use of Sinequan on a once-a-day dosage regimen in geriatric patients, patients with intercurrent illnesses, or patients taking other medications should be adjusted carefully, based on the patient's condition. This is especially important if the patient is receiving other medications with antichol inergic effects. Adverse Reactions Sinequan is generally well tolerated. The following adverse reactions have been reported:

Behavioral Effects: agitation, restlessness, excitement, activation of psychotic symptoms and toxic confusional state. Anticholinergic Effects: dry mouth, blurred vision, constipation, and genito-urinary disorders. Central Nervous System Effects: drowsiness, insomnia, extrapyramidal symptoms. Cardiovascular Effects: dizziness, hypotension, tachycardia. Miscellaneous: fatigue, weight gain, increased sweating and other secretory effects, nausea, heartburn, rash and pruritus, paresthesia, edema, flushing, chills, tinnitus, photophobia, decreased libido. Dosage and AdministratIon An optimum daily dosage of Sinequan depends on the condition which is being treated and the response of the individual. Some patients respond promptly; others may not respond for 2 weeks or longer. An initial dosage of 25 mg t.i.d. is recommended in most patients. This dosage should be increased as required by 25 mg increments at appropriate intervals until a therapeutic response is obtained. The usual optimum dosage range is 100-150 mg per day. In some patients, up to 300 mg per day may be required, but there is rarely any benefit to be obtained by increasing this dosage. In elderly patients it is advisable to proceed more cautiously with dosage increments and to initiate treatment with a lower dosage. Once a satisfactory therapeutic response has been obtained, it is generally possible to reduce the dosage and still maintain this effect. For maintenance therapy in depressed patients, the total daily dosage, up to 150 mg, may be given on a once-a-day schedule. This dosage should be established as described above and should preferably be given at bedtime. Oral Concentrate: SINEQUAN Oral Concentrate is available in 120 ml bottles with an accompanying dropper calibrated at 5 mg, 10 mg, 15 mg, 20 mg, and 25 mg. Each ml contains doxepin H Cl equivalent to 10 mg doxepin. SINEQUAN Oral Concentrate should be diluted with water or suitable juices just prior to administration. Preparation and storage in bulk dilutions is not recommended. Dosage Forms SINEQUAN Capsules contain doxepin hydrochloride equivalent to 10, 25, 50 and 100 mg of doxepin in bottles of 100 and 500. SINEQUAN Oral Concentrate is available in bottles of 120 ml. Each ml of SINEQUAN Oral Concentrate contains doxepin hydrochloride equivalent to 10 mg of doxepin.

Bibliography 1. PRODUCT MONOGRAPH

2. GERSON, IM. et al: Non-Antagonism of Antiadrenergic Agents by a Dibenzoxepine, Diseases 01 the Nervous System, Volume 31, pp. 780-782, November 1970. 3. PRANGE, A.J., Jr.: The Use of Antidepressant Drugs in the Elderly Patient. In Eisdorfer, c. and Fann, W.E. (Eds): Psychopharmacology and Aging, New York, Plenum Press, 1973, P. 232. 4. AYD, F.J., Jr.: Maintenance Doxepin (Sinequan) Therapy for Depressive Illness, Diseases 01 the Nervous System, Volume 36, No. 4, pp. 109-114, March 1975. 5. AYD, F.J., Jr.: Recognizing the Depressed Patient, New York, Grune & Stratton, Inc., p. 26, 1961. 6. GOLDBERG, H.L and FINNERTY, R.J.: Doxepin in a Single Bedtime Dose in Psychoneurotic Outpatients, Arch. Gen. Psych., Vol. 31, p. 513, October 1974. 7. SMITH, J.A. and RENSHAW, D.C.: Insomnia - A Signal Symptom, Scientific Exhibit presented at the 127th Annual Meeting of the American Psychiatric Association, May 5-9, 1974. 8. DAVIES, B.M.: The Effects on the Heart of Different Tricyclic Antidepressants, Reprinted from "Sinequan' (doxepin HCI) Excerpta Medica, 1975. 9. Official Health Protection Branch Product Monographs for amitriptyline, clomipramine, desipramine, nortriptyline, protriptyline, trimipramine and imipramine. trademark authorized user

PHARMACEUTICAL DIVISION Montreal. Canada

984 CMA JOURNAL/JUNE 5, 1976/VOL. 114

is reduced without diagnostic accuracy being compromised.4 Having ruled out invasive cancer, the physician can then treat the patient, using either cryosurgery or electrocautery. Cryosurgery is effective in 90% of patients.5 A recommendation made in the report that deserves emphasis is that uniform terminology be used for reporting. Papanicolaou divided cytologic smears into five classes. The number system of reporting abnormalities is not satisfactory and should be abandoned. A verbal report, in which the cytologist states what he anticipates the histologic lesion to be, is recommended so that satisfactory documentation, cross-referencing and follow-up assessments can be made. The report provides evidence that screening programs are indeed effective in reducing mortality from carcinoma of the cervix and that this effectiveness is directly related to the proportion of the population screened. It places on the practitioner's shoulders the responsibility of bringing into the program women who have never been screened, and of modifying the frequency with which women are called upon to return for examination, depending upon their degree of risk. Specialized clinics are already operating in many centres across Canada where gynecologists trained in colposcopy can evaluate an abnormal smear. A tissue diagnosis can be obtained without the traditional cone biopsy so that in cases of dysplasia and carcinoma in situ further progress of the disease can be prevented by simple therapeutic procedures. This is especially important because of the tendency for preinvasive lesions to occur at a younger age than previously noted, an age when years of childbearing lie ahead. It appears that the majority of invasive cancers of the cervix could be prevented by more efficient use of our existing screening facilities, so that detection and treatment could be carried out in the preinvasive state of this disease. D.R. Pos'Km, MD 1'RCS(C] birector Division of gynecology Royal Victoria Hospital Montreal, PQ

References 1. Emuix HK. Bovas DA, WORTH AG: Cervical cancer detection an British Columbia. I Obstet Gynaecol Br Commonw 75: 392, 1968 2. Bo.as DA, Fanuix IlK, Locx DR: The significance of in situ carcinoma of the uterine cervix. Br Med 1 1: 203, 1962 3. Koss LG: Concept of genesis and development of carcinoma of the cervix. Obstet Gynecol Surv 24: 851, 1969 4. STAFL A, MATTINGLY RF: Colposcopic diagnosis of cervical neoplasia. Obstet Gynecol 41: 168, 1973 5. TOWNSEND DE, OSTERGARD DR: Cryocauterization for preinvasive cervical neoplasia. I Reprod Med 6: 171, 1971