Document LJNQpKjZ8aV910Kk1K0e200Rw

FILE NAME: Talc (TALC) DATE: 1982 DOC#: TALC024 DOCUMENT DESCRIPTION: Medical Journal Article - Ovarian Cancer and Talc $ g 03 ? QO- j' Ovarian Cancer and Talc O : CO 3 ) A Case-ControI Study DANIEL W. CRAMER, WILLIAM R. WELCH, MD, ROBERT E. SCULLY, MD,1 AND CAROL A. WOJCIECHOWSKI, RN* 03 1 ~o * Opportunities for genital exposure to talc were assessed in 215 white females with epithelial ovarian C03 N in * r * a l r l l l l C ntr01 T T fr m thC general population matched by age, race, and residence. Ninety-two (42.8%) cases regularly used talc either as a dusting powder on the perineum or on sanitary CL j napkms compared with 61 (28.4%) controls. Adjusted for parity and menopausal status, this difference yielded a relative n sk of 1.92 (P < 0.003) for ovarian cancer associated with these practices. Women who had regularly engaged m both practices had an adjusted relative risk of 3.28 (P < 0.001) compared JD * to women with neither exposure. This provides some support for an association between talc and ovarian 2> I TOU" reirHonh fPt |hefS,ZedK beCaUS\ 0f thC S,milarity of ovarian cancer t0 mesotheliomas and the chemical relation of talc to asbestos, a known cause of mesotheliomas. The authors also investigated opportunities for potential talc exposure from rubber products such as condoms or diaphragms or from pelvic surgery No significant differences were noted between cases and controls in these exposures, although the intensity of talc exposure from these sources was likely affected by variables not assessed in this study. Cancer 50:372-376, 1982. 0SZ3 5* H ' H E p o s s ib il it y that ovarian cancer may be caused 0J ; I by exposure to certain hydrous magnesium sili --^cates such as talc and asbestos has been raised by sev- g j eral researchers.1-3 The lack of epidemiologic studies o ' regarding this hypothesis prompted us to investigate =<J italc exposure in a case-control study of ovarian cancer JO- 'i O ^ From the Departments of ` Obstetrics, tGynecology, and PatholT3 gy. Boston Hospital for Women, Division of the Brigham and . Women's Hospital, the Department of Epidemiology, Harvard 8 sSch001 of Publ'c Health and the 'Department of Pathology, Massa chusetts General Hospital, Harvard Medical School, Boston, Mas5 sachusetts. Supported by Grant Number 5-ROl CA24209, awarded by the S'cc*"National Institutes of Health, DHEW. " Address for reprints: Dr. Cramer, Department of Obstetrics and = Gynecology, Brigham and Women's Hospital, Boston, MA 02115. g This study could not have occurred without the generous partici_ pation of many clinicians and institutions in the greater Boston area including: Dr. Emanuel Friedman of the Beth Israel Hospital, Drs. 7c Robert Knapp and Thomas Griffiths of the Brigham and Women's E Hospital and Sidney Farber Cancer Institute, Dr. Arthur Hassett of jz the Brockton Hospital, Dr. Joel Rankin of the Framingham Union t - Hospital, Dr. Edward Copenhaver of the Lahey Clinic Foundation, Dr. James Nelson of the Massachusetts General Hospital, Dr. Clem ent Yahia of the New England Deaconess Hospital, Dr. Lalita Gandbhir of the Pondville Hospital, Dr. James Whelton of Saint Elizabeth's Hospital, Dr. Stephen Alpert of the Salem Hospital, Dr. Richard Hunter of the University of Massachusetts Medical School. The su perb clerical and technical assistance of Ms. Eileen McManus, Ms. Sally Cassells, and Ms. Christine Peters is also gratefully acknowl edged. Accepted for publication December 29, 1981. Methods The cases studied were women with ovarian cancer, diagnosed between November 1978 and September 1981 and identified through the pathology logs or tumor boards of twelve participating hospitals in the Greater Boston area. The study was restricted to English-speak ing residents of Massachusetts ranging in age from 18 to 80 years. During the study period, 297 eligible cases were identified. Physicians denied permission to contact their patients in 13 instances. Fourteen patients de clined to participate, and 14 other patients had died or moved before they could be contacted. For each of the 256 interviewed cases, slides of the surgical specimens were reviewed by two authors (W.R.W. or R.E.S). Eighteen cases were excluded as nonovarian primaries. Each ovarian tumor was classi fied according to the Histological Classification of Ovarian Tumors of the World Health Organization.4 The present analysis was restricted to 215 white women with epithelial cancers, including 39 with tumors of borderline malignancy and their matched controls. Control cases were identified through the M assachu setts Town Books, annual publications that list residents by name, age, and address. Controls were selected ran domly from those women who matched cases by pre cinct of residence, race, and age within two years. A d ditionally, it was required that a subject be excluded 0008 543X/82/0715/0372 $0.75 American Cancer Society as a control i rectomy, but prior hystere Women who confident in had been re could not b< stance. Won , were includt lection of tl were eventu controls ide (12%) of th had moved ' phones. Tv because o f. while 20 (4 speak Eng (33%) refu acterized a matched w one refusa or more rt lntervie number of history, m - exposures 1 of several i exposure 1 J or perinea 3 confoundi : associate! Mantel-l and Boio as the m analysis 1 al.6 was The a SEM) f> Ext ; Pelvic sur ' Pelvic sur : to1951 Use of ct : Use of ii. 1 *Adju j (pre- anc: ;i i I I I an cancer, September 'S or tumor ie Greater ish-speake from IX -tibie cases to contaci tients de ad died or Jes of the | authors eluded as as classi cal ion of nization.'1 te women umors of Trols. assachuresidents cted ran > by pre tars. Adexcluded Vo. 2 Ovarian Ca and Talc Cramer et al. 373 as a control if she had had a bilateral salpingo-oophorectomy, but subjects were not excluded because of Table 1. Characteristics of Cases and Controls prior hysterectomy or other types of pelvic operations. Women who had had pelvic operations were generally Cases (Total = 215) Controls (Total = 215) confident in their knowledge of whether their ovaries Characteristic No. % No. % had been removed, but the nature of the operations could not be verified by hospital records in each in Educational level (completed stance. Women whose statements could not be verified were included or excluded on the basis of their recol lection of the surgery. The 215 controls in this study college) Religion (Roman Catholic) Marital status 48 22.3 49 22.8 126 58.6 128 59.5 were eventually obtained from a total of 475 potential (never married) 46 21.4 24 112 controls identified through the Town Books. Fifty-six Nulliparous Menopausal status 78 36.3 39 18.1 (12%) of the total could not be reached because they (postmenopausal*) 137 63.7 129 60.0 had moved, died, or had disconnected or unlisted phones. Twenty-nine (6%) of the total were ineligible because of a history of bilateral salpingo-oophorectomy, * Postmenopausal at time of diagnosis for cases or for interview for Controls. while 20 (4%) were of the wrong age or race or did not speak English. Of the total potential controls, 155 (33%) refused to participate. If the 215 cases are char acterized as to ease of matching, 121 (56%) cases were matched with no refusals, 58 (27%) were matched after one refusal, and 36 (17%) were matched only after two or more refusals. Interviews were conducted personally to assess a number of factors from the menstrual and reproductive history, medical and family history, and environmental exposures. This report will deal only with the results of several questions related to potential or definite talc exposure by way of contraceptive practices, operations, or perineal hygiene. Subjects were stratified by potential confounders described below, and adjusted relative risks associated with these exposures were calculated by the Mantel-Haenszel procedure as adapted by Rothman and Boice.5To accommodate other confounders as well as the matched design in the data collection, logistic analysis for matched data as described by Breslow et al.b was also employed. 53.5 (1.0) years. Table 1 shows other characteristics of subjects. Controls were comparable to cases in educa- * tional level and religion. Cases and controls differed ? significantly in marital status and parity with parity b being the more important discriminator between them, a Sixty-four percent of the cases were postmenopausal at 4 the time of diagnosis, whereas 60% of controls were f postmenopausal. Of these, 15 cases and 20 controls had had an artificial menopause. Parity and menopausal " status were considered important potential confounders in this analysis and were adjusted for as described above. Relative risks associated with potential talc exposure from contamination on rubber products are explored in Table 2. Although surgical gloves of recent vintage j are dusted with starch, talc contamination may still be ` found.7 Thus, a history of pelvic operations (appendec tomy, cesarean section, hysterectomy, and other oper ations on internal genital organs other than bilateral ^ salpingo-oophorectomy) was determined in cases and I controls. Excluding operations associated with the di- ? Results The average age (and standard error of the mean, SEM) for cases was 53.2 (1.0) years and for controls, agnosis or treatment of the ovarian cancer among the f cases, no excess in the occurrence of pelvic operations was noted. The greatest opportunity for talc exposure from surgery occurred before 1950, when talc was the | Table 2. Relative Risks (RR) for Common Epithelial Ovarian Cancers Associated with Potential Talc Exposure ______________________ from Contamination on Rubber Products Cases Controls Exposure Pelvic surgery Pelvic surgery (prior to 1950) Use of condomst Use of diaphragmt Total 215 215 169 169 No. (%) with exposure 78 (36.3) 51 (23.7) 19 (11.2) 37 (21.9) Total 215 215 191 191 No. (%) with exposure 75 (34.9) 48 (22.3) 30 (15.7) 35 (18.3) Crude RR 1.06 1.08 0.68 1.24 Adjusted RR* 1.17 1.12 0.77 1.19 95% Confidence limits (0.76-1.79) (0.69-1.82) (0.41-1.44) (0.69-2.05) l ^ dnHS!lt^ n Pl rit,!'inUllipar US' Par US) 3nd menPausal status + Restricted to subjects who had ever been married. The material on this page was copied from the collection of the National Library of Medicine by a third party and may be protected by U S Copyright law 374 -- i i l _ f ! Lative Risks (RR) Associated with Using Talc for Stn A ---------- -------- ---------Diaphragm Users* by Duration Cases Controls of Use of Diaphragm Duration of OCL ' diaphragm use O Total diaphragm use less than five years Total diaphragm use five or more years IB All users QJ o Q<u- : status".dudes a" WOme" -O Total No. (%) who used talc on diaphragm Total 13 6 (46.2) 21 27 16 (59.3) 19 40 22 (55.0) 40 ---------------- - e d diaphragm regardless of marital No. (%) who used talc on diaphragm Crude RR Adjusted RRt 8 (38.1) 1.39 1.82 11 (57.9) 1.06 1.23 19 (47.5) 1.35 1.56 + Adjusted for parity and menopausal status. 95% Confidence limits (0.42-8.00) (0.36-4,17) (0.62-3.88) IS S a ss * * CL o cant1^Condoneither d`fference was statistically signifi5 Cant' Condom use is not necessarily associated with ? , I , T S"rH ,N,,' brands f wS Hygienic practices involving talc were also st,,H- a useTta`lc"y' WeHinq"ired whe,h" women had rega uulaarrlly, dLusTtedh sanS"itnargyPnWapdkeirns"w,hiteh Ptoarlicno(nTna,bole g Ninety-two (42.8%) of the cases had tale * 4)' either or both of these routes compared wi h l f " 28 4 ') f adj"S,cd relati- risk was ," : ,p ) with 95% confidence limits of 1 27-2 8Q - pared t subjects who had nejther ex ' ^ aallce ffoorr tdiunst?ing or 4o8n (n2a2p'3k%in)s CbOunttrnoolst hbaodtheitThhei/susree ference yielded an adjusted relative risk o f 1(1 r 1 We .nguTrld3 rpralite r f d r S 8 !he dlaP^ra8m with talc for storage after use (Table i a" SUbjeCtS who had use(t a diaphragm, there 'o * j- 1^ni^Can^ excess cases who regularlv I 6" d,aPhr^ m - " g talc, nor was any" g S i C r i L 8 f hSCu Hd W^ h thlS practice observed among women I I e life " f r l0n8Cr t o S T S i tsp d k f T klS exPsure can be adequately as S ' greater detail is needed including frequency of was of borderline significance (P = o 06) T h e" W1`Ch nsk occarrc, in wome,, who tad both wxho hhaaddpr trz -a--n-d---o-n-conam4pkairnesd) to women .o w,,i;;: neither exposure. Thirty-two (14 9%/n)\ nf ro.,ka 7wTMere "in Jthis category cCoommPpaar-edd wwiitthh 1133((6600%%) c)o^nD" olT or a3n0 aaddjjUusStteedd rreellaattlivvee rriisskk of 3.28 (p < 001)' and-9s-%- confidence imits of U s 6 t t tl , } d 95% ToJ |e and whether the powder was washed off prior to Oa). | , Ur ermore> contraceptive jellies used with the o ;. - 03 ?' ltract. <5D 4! affec` *he `ransport f ,a k in *be r--e-1-3--------T--a--b--l--e----4-CO t Epithe,.., women without perineal exposure to tafe (Table 5) dIn^rTadd,,,on,. the proportion wof vcaasseess wwiittnh ttulmo orrss o" h,,r ^ n,,d of 123 cases withoat the exposure had , ,, L rs ,,) hor C e ,, A,, ,, w --ith Talc Exposure in Perineal Hva.Vn. O * "TO it 0> rz No perineal exposure Any perineal exposure * Total = 215) ltrols Total = 215) ide rr Adjusted RR* 95% confidence limits * Adjusted for parity 123 (57.2%) 154 (71.6%) 1 -- -- and menopausal status. 92 (42.8%) 61 (28.4%) 1.89 1.92 (1.27-2.89) As dusting powder but not on napkins Types of perineal exposure On napkins but not as dusting powder Both on napkins and as dusting portier 43 (20.0%) 34 (15.8%) 1.58 1.55 (0.98-2.47) 17 (7.9%) 14 (6.5%) 1.52 32 (14.9%) 13 (6.0%) 3.08 if j No. 2 I derline maligi j the talc expos The argum eludes four eh talc and asbe peritoneal me epithelial ova ability of tak talc is a specii related to sevc in nature witl may be cont powders form Epidemiolo and pleural ai exposure.10 A been reported with the amo deposits work induce ovaria and suggests asbestos expi sotheliomas a , ruff12 further ; ized the pelv ; that environn i cavity via tht observed that immediately from the fallt ticism, the fin and abnorma that can ente Although i has emerged participants i for epidemio exposure. In of the epithel of potential t nificant findir cer and hygu the perineum regularly had had used it o fold increase exposure. Se in interpretin The obsen characteristic cancer and cc may confoun . Vo!. 50 So. 2 Ovarian Ca and Talc Cramer et al. 375 The material on this pape was copied from the collection of the National Library of Medicine by a Ihird party and may be protected by U S Copyright law phrugn onfidencc im lis 2-8.00 j 6 4.17) 2- 3.88 ) studied. egularl) ! or regtble 4). sure by (28.4'.;') 1.92 (P 39 com `. Sixty ler used his dif\ which greatest es (use women )f cases ontrols, nd 95'i charac'erineal n those ible 5). of bor ith and 0 8'-;) of bor- kins and powder ^ ) ' ) 42) jerline malignancy compared to 17 (18%) of 92 with he talc exposure. Discussion The argument linking talc and ovarian cancer in,-ludes four elements: the chemical relationship between ale and asbestos, asbestos as a cause of pleural and peritoneal mesotheliomas, the possible relation between epithelial ovarian cancers and mesotheliomas, and the ability of talc to enter the pelvic cavity. The mineral .ale is a specific hydrous magnesium silicate chemically related to several asbestos group minerals and occurring mnature with them. Generic "talc" is seldom pure and aiay be contaminated with asbestos, particularly in powders formulated prior to 1976.8'9 Epidemiologic studies have clearly linked lung cancer and pleural and peritoneal mesotheliomas with asbestos exposure.10An excess of similar pulmonary lesions has been reported in talc workers and seems to be correlated with the amount of asbestos contamination in the talc deposits worked." Graham and Graham1were able to induce ovarian neoplasms in guinea pigs with asbestos ind suggested that ovarian cancer could be related to asbestos exposure, noting the similarity between me sotheliomas and ovarian cancers. Parmley and Wood ruff12 further emphasized this similarity and popular ized the pelvic contamination theory, which proposed (hat environmental carcinogens might enter the pelvic cavity via the genital tract. Years earlier it had been observed that inert carbon particles placed in the vagina immediately prior to hysterectomy could be recovered from the fallopian tubes.13Although greeted with skep ticism, the finding of talc particles embedded in normal and abnormal ovaries suggests that talc is a substance that can enter the pelvic cavity via the vagina.2 Although no consensus concerning the risks of talc has emerged from letters, editorial and articles,3,14"16 participants in the discussion have agreed upon the need for epidemiologic studies of ovarian cancer and talc exposure. In this case-control study of ovarian cancer of the epithelial variety, we investigated several sources of potential talc exposure. Among these, the only sig nificant finding was an association between ovarian can cer and hygienic practices involving the use of talc on the perineum. It is especially notable that women who regularly had both dusted their perineum with talc and had used it on sanitary napkins had more than a three fold increase in risk compared to women with neither exposure. Several potential biases must be considered in interpreting this association. The observation by Wynder et al.'1 that menstrual characteristics may differ between women with ovarian cancer and controls might suggest that such differences may confound the association between perineal use of Table 5. Characteristics of Ovarian Cancer in Women with and without Perineal Exposure to Talc No perineal use of talc Any perineal use of talc No. (%) No. (%) Serous Mucinous Endometrioid and clear cell Other and undifferentiated Total 66 (53.7) 16 (13.0) 32 (26.0) 9 (7.3) 123 (100) 45 (48.9) 14 (15.2) 24 (26.1) 9 (9.8) 92 (100) talc and ovarian cancer. We found that menstrual char acteristics of cases and controls were virtually identical in this study. Fifty-three (24.7%) cases complained of moderate or severe dysmenorrhea compared to 56 (26.0%) controls. Twenty-five (11.6%) cases com plained of irregular periods compared to 32 (14.9%) controls. The average numbers (and SEM) of days of flow and cycle length were, respectively, 4.9 (0.1) and 28.9 (0.3) days for cases and 4.9 (0.1) and 29.6 (0.3) days for controls. Since entry of talc into the pelvic cavity is prevented by hysterectomy or tubal ligation, it might also be ar gued that the inclusion of subjects with pelvic surgery in the analysis may obviate any association between talc and ovarian cancer. It should be noted that such surgery generally occurred near the end of reproductive life for both cases and controls, probably after most significant talc exposure had already occurred. The exclusion of such subjects from the analysis did not substantially alter the observed associations. For example, the ad justed relative risk for the use of talc both on the per ineum and sanitary napkins was 2.79 (P < 0.003) in the group without pelvic surgery compared to 3.28 observed for the entire group. In terms of other confounders, the association per sisted after adjustment for menopausal status and par ity. We also applied multivariate logistic regression for paired observations.6The maximum likelihood estimate of relative risk associated with any perineal use of talc was 1.61 (1 = 0.03) with 95% confidence limits of 1.04 2.49 after simultaneous adjustment for religion, marital status, educational level, ponderal index, age at men arche, exact parity, oral contraceptive or menopausal hormone use, and smoking. Our sample of cases represents more than 50% of ovarian cancer cases diagnosed in Boston residents in the study period. Therefore, it is difficult to conceive of a plausible bias in the selection of cases that would yield this excess use of talc. There is reason for concern that the high refusal rate among the controls may have introduced a selection bias among the controls. But, 376 C a n c e r July 15 1982 Vol. 50 | The material on this paqe was copied from the collection of the National Library of Medicine by a third party and may be protected by U S Copyright law when we restricted the analysis to the 121 cases who were matched without a control refusal, we again found a significant association between talc use and ovarian cancer. For women who had used talc both in dusting and on the perineum we found an adjusted relative risk of 2.44 (P < 0.05). Interviewer bias is also unlikely to explain the association. Of the 18 women who were initially interviewed as ovarian cancer cases but later excluded as having metastatic tumors to the ovary, only one (5.6%) had both perineal and napkin exposure as compared with 15% in cases and 6% in controls. Experimental data which might bear on the carci nogenicity of talc come primarily from models using pleural implantation of various minerals in rats.18These data suggest that carcinogenicity is dependent primarily upon the shape of the particles with long thin fibers such as those occurring in crocidolite asbestos being most carcinogenic. Talc consists primarily of plates but may contain fibers, although voluntary guidelines to limit the content of asbestisform fibers in consumer tal cums were proposed by the cosmetics industry in 1976.19 ; If talc is involved in the etiology of ovarian cancer, it is not clear whether this derives from the asbestos jcontent of talc or from the uniqueness of the ovary `which might make it susceptible to carcinogenesis from both talc and other particulates. With ovulation en trapment of the surface epithelium of the ovary into the ovarian stroma occurs. If present, talc or other partic ulates might be incorporated into these inclusion cysts. Apparently implantation of foreign bodies into the luInens of epithelial lined organs provides a favorable invironment for carcinogenesis.20 Alternatively, talc might serve to stimulate entrapment of the surface ep ithelium and act in the same way that "incessant ovu lation" has been proposed as an etiologic factor for ovarian cancer.21 Given the histologic and clinical di versity of ovarian cancer, talc exposure is unlikely to be the only cause. Undoubtedly, reproductive experi ences such as pregnancies and, perhaps, oral contra ceptive use play a role in its etiology.21-23 The possibility that talc exposure interacts with these variables de serves further investigation. " It is hoped that this report will stimulate further study of talc exposure in relation to ovarian cancer. Animal Studies would be helpful to determine whether and un der what circumstances ovarian tumors may be induced by various talc preparations. Epidemiologic studies should focus on opportunities for excessive vaginal con tamination with talc such as when it is repeatedly used ip perineal dusting powders or sprays and in or on tam pons, sanitary napkins, or other products intended for intravaginal use. More precise details on the exact na ture and frequency of the exposure and the amount and specific brand of powder used are essential. Opportu nities for talc exposure are widespread and pervasive,24 but that should not discourage epidemiologists from studying this potentially important exposure in relation to ovarian cancer. REFERENCES 1. Graham J, Graham R. Ovarian cancer and asbestos. Environ Res 1967; 1:115-128. 2. Henderson WJ, Joslin CAF, Turnbull AC, Griffiths K. Talc and carcinoma of the ovary and cervix. J Obstet Gynaecol Br Commonw 1971;78:266-272. 3. Longo DL, Young RC. Cosmetic talc and ovarian cancer. Lancet 1979; ii:349--351. 4. Serov SF, Scully RE, Sobin LH. International Histological Clas sification of Tumours, No. 9. Histological Typing of Ovarian Tu mours. Geneva, World Health Organization, 1973. 5. Rothman KJ, Boice JD. Epidemiologic analysis with a program mable calculator. NIH Publication No. 79-1649, 1979. 6. Breslow NE, Day NE, Halvorsen KT, Prentice RL, Sabai C Estimation of multiple relative risk functions in matched case control studies. Am J Epidemiol 1978; 108:299-307. 7. Henderson WJ, Hamilton TC, Griffiths K. Talc in normal and malignant ovarian tissue. Lancet 1979; i:499. 8. Cralley LJ, Key MM, Groth DH, Lainhart WS, Ligo RM, Fi brous and mineral content of cosmetic talcum products. Am Ind Hvg Assoc J 1968; 350-354. 9. Rohl AN, Langer AM, Selikoff IJ, Tordini A, Klimentidis R. Consumer talcums and powders: Mineral and chemical characteriza tion. J Toxicol Environ Health 1976; 2:255-284. 10. Selikoff IJ, Hammond EC (eds.). Health hazards of asbestos exposure. Ann N Y Acad Sci. 1979; 330:1-179. 11. Kleinfeld M, Messite J, Zaki MH. Mortality experiences among talc workers: A follow-up study. J Occup Med 1974; 16:345 349. 12. Parmley TH, Woodruff JD. The ovarian mesothelioma. Am J Obstet Gynecol 1974; 120:234-241. 13. Egli GE, Newton M. The transport of carbon particles in the human female reproductive tract. Fertil Steril 1961; 12:151-155. 14. Anonymous. Cosmetic talc powder. Lancet 1977; :i:1348. 15. Newhouse ML. Cosmetic talc and ovarian cancer. Lancet 1979; ii:528. 16. Roe FJC. Controversy: Cosmetic talc and ovarian cancer Lan cet 1979; ii:744. 17. Wynder EL, Dodo H, Barber HRK. Epidemiology of cancer of the ovary. Cancer 1969; 23:352-370. 18. Stanton MF, Layard M, Tegeris A, et al. Relation of particle dimension to carcinogenicity in amphibole asbestoses and other fibrous minerals. J Natl Cancer Institute 1981; 67:965-975. 19. C.T.F.A. Specification. Talc, cosmetic: Cosmetic, toiletry, and fragrance association, Inc. Issue 10-17, 1976. 20. Brand KG, Johnson KH, Buoen LC. Foreign body tumorigenesis. CRC Crit Rev Toxicol 1976; 4(Oct):353-394. 21. Casagrande JT, Pike MC, Ross RK, Louie EW, Roy S, Hen derson BE. Incessant ovulation and ovarian cancer. Lancet 1979, ii: 170--172. 22. Newhouse ML, Pearson RM, Fullerton JM, Boesen EAM, Shannon HS. A case control study of carcinoma of the ovary. Br J Prev Soc Med 1977; 31:148-153. 23. McGowan L, Parent L, Lednar W, Norris HJ. The woman at risk for developing ovarian cancer. Gynecol Oncol 1979; 7:325-344. 24. Blejer JP, Arlon R. Talc: A possible occupational and envi ronmental carcinogen. J Occup Med 1973; 15:92-97. I. Evidenc RICHARD REIf A (S A. 81 ol si tr ot st IV tl b e Early si cioecoi of cervical c infections a 3 Potentiall herpes sim (CMV),5 ar lation that prompted b between get results of ti sibly analog i First presen - the Cervix: Bn ton, South Ca From the D University Scb of Pathology, Address for ment of Obsti ! West Outer F : The author ; this manuscri; 1 and Grace Sc fellow librari; Richardson, F of medical re and to Judy 1 Accepted F