Introduction

1. Introduction Occurrence of cervical intraepithelial neoplasia is investigated for the first time in Jordan. Related factors are studied, and the value of routine Papanicolaou (Pap) smear is emphasized. A brief review of literature will be presented .

2. Materials and Methods Alcohol-fixed Pap smears were received by the Consulting Medical Laboratories in Amman - Jordan for either routine checkup or gynecologic complaints. In other cases, no reason for referral was stated. Smears with inadequate cell yield were repeated.

3. During the period from 1982 through 1991, a total of 10,659 cases were divided into Jordanian and non-Jordanian groups, 1 and 2, respectively. Group 2 consisted of 2916 resident non-Arab females who were either employees or house wives

4. Every request form gave: The patient's name. The patient’s age Referring doctor Previous smears. Interested gynecologists also provided the following data: Date of last menstrual period . Menstrual history. Marital status.

5. Duration of marriage. • Number of children. • Place of birth. • Whether husband is circumcised , and • Any specific gynecologic complaints. • Social status was judged by the place of residence and the husband's occupation.

6. Referring gynecologists as a rule used a wooden Ayre's spatula for specimen collection. Staining of slides was made by Papanicolaou's method¹. In all cases, smears were screened by a consultant pathologist under 10X followed by 40X high power field covering all areas.

7. Samples were accepted as satisfactory when containing an adequate number of squamous metaplastic cells. A maturation index was given whenever possible. Neoplastic change was reported in the three-grade system and confirmed in each case by at least one repeat smear. • Grade I CIN corresponded to low-grade squamous intraepithelial lesion (LSIL) • While Grades II and III corresponded to high-grade squamous intraepithelial lesion (HSIL) in the Bethesda System².

8. Cases with minimal cytologic changes which corresponded to reactive changes in intermediate, parabasal or endocervical cells consisted mainly of slight enlargement of nuclei without hyperchromatism. Follow-up was made in each case with minimal change. In this series,28 females were diagnosed as having had CIN Duplicated cases were accounted for. Cytohistologic correlation was made whenever possible. Follow-up could be made in 27 females with CIN.

9. Distribution of CIN cases by age and gradeTable 1:

10. Results During the period of 1982 to 1991 inclusive, 10,659 females entered this study : 4048 (38%) were for routine checkup, 3519 (33%) had gynecologic complaint (s),and 3092 (29%) had no specific reason stated. Of the total number: 7743 females (Group 1) were Jordanian (73%) 2916 (Group 2) were non-Jordanian (27%). Eighty-eight cases of CIN were in Group 1 33 were in Group 2 With a frequency rate of 1.1% in each group (Table 1).

11. The ages of 11 females with minimal cytologic atypia ranged from 24 to 48 years with a mean of 34years. In squamous cells, minimal cytologic change was associated with inflammation or atrophy While in endocervical cells, it was associated with the use of an IUD.

12. Follow-up showed resolution in every case within one year. Twenty-eight cases diagnosed abroad as having CIN had no report to indicate cytologic grad or any given treatment. Of the 28 23 were Jordanian Five were non-Jordanian. The former were ages 20 to 40 with a mean of 30 years.

13. Table 2 shows the estimated annual incidence rates of CIN for Jordanian females in different age groups ; In those 15 to 59 years , the estimated annual incidence rate was 114 per 100,000. Peak incidence reached 184 per 100,000 in those 35 to 49 years of age, of whom 2649 went purely for routine checkup with discovery of CIN in one case, leading to an estimated incidence of 49 per 100,000 in this latter patient population .

14. Estimated incidence rates of CIN in Jordanian females.*Table 2:

15. Cytohistologic correlation could be made in 23 cases . In 17 ( 70 % ) of these, the cytologic grade correlated with the histologic diagnosis , representing two , five and 10 cases in Grades I, II and III respectively . In each of the remaining six cases, the cytologic grade trailed one step behind histology : one , three and two cases corresponding to Grades I versus II , II versus III , and III versus invasive carcinoma, respectively .

16. Follow–up was made on 27 of 121 CIN cases for periods of 18 to 39 months , an average of 30.3 months . Of those 27 females , 14 , five and eight respectively attended two, three and four times for follow–up . During the period of this study, three females with initially negative Pap smears developed smears positive for neoplasia after an average follow – up of 25 months ; their mean age was 36 years . In the other 24 females, follow – up periods averaged 31 months . Conization and cautery were the principal methods of treatment employed . All 27 females are doing well and show no evidence of neoplasia after treatment .

17. The rate of circumcision in spouses of CIN cases was 79 % ( 95 of 121 ), compared to 89% in non-CIN partners ( 1035 of 1163; p value =<0.01 ) . In CIN versus non-CIN cases , age at marriage was 17.4 versus 23.5 and 20.2 years versus 24.7 years in Jordanian and non- Jordanian females respectively . In both populations, age at and duration of marriage , breast feeding, and menstrual disorders showed no significant difference in females with and without CIN .

18. The average number of childbirths in Jordanian females with and without CIN was 6.2 and 5.4 versus 2.6 and 2.4 for non- Jordanian females with and without CIN . About half the cases in each population group used the contraceptive pill . Table 3 shows distribution of the two population groups according to social class . Social class showed no bias for frequency of CIN in their population groups .

19. Socioeconomic distribution of CIN and non CIN cases Table 3.

20. In recent years , Pap smears have proven effective screening for cervical neoplasia, and were instrumental in reducing reducing mortality from cervical cancer . This 10- year evaluation of Pap smears will enable us to compare females in Jordan with females from other countries and see if they need repetition of Pap smears at regular intervals. Discussion

21. Frequency of CIN was 1.1% in groups 1 and 2 alike , with average ages of 42 and 34 years respectively . This suggests group 2 female are susceptible at an earlier age , which is in agreement with other studies. The higher average age in Jordanian females probably reflects a difference in sexual habits . Absence of CIN in our females who were above 60 is in accordance with other reports in which CIN de novo was either infrequent or absent in females over 50 years of age.¹¹’¹²

22. Frequency of CIN in screened groups within selected patient populations were relatively high; for example , 8% in one California study on emergency ward patients ¹³. While in another study from Seattle , development of CIN at two years was seen in 3% and 28% of HPV negative and positive females, respectively .

23. Table 2 shows a stepwise increase of incidence rates in females between the ages of 20 and 49 years with a fall during the sixth decade . An incidence of 49 per 100,000 in the routine checkup group within our patient population and peak incidence in the 35 to 49 age group stress the value of Pap smears in this female community . An incidence of 49 per 100,000 in what we regard as a screened population was unexpectedly high and may not necessarily reflect CIN incidence in the general population.

24. In a multicenter American study , the incidence of CIN was 31.2 and 31.5 per 100,000 black and white females , respectively; while in a red Indian population , it reached 38.2. In contrast , screening of 38,026 females attending Bangkok Siriraj Hospital outpatient clinics yielded an incidence rate of 213 per 100,000 thais. The number of CIN cases showed progressive increase during this study period but this corresponded to an annual increase in the total number of females screened for cervical neoplasia.

25. We believe we had not overdiagnosed cases since cytology correlated with histology in 70%; while in all the remaining cases , cytology undergraded the lesion as judged by histology . • Minimal cytologic change presented some uncertainty at initial examination but changes in all 11 cases proved reactive and transient on follow–up, since all cases became normal within 12 months, which justified their exclusion from the cervical neoplasia group .

26. Cases with mild cell atypia were reported to pose no risk for future development of cervical neoplasia. In 28 females , CIN was diagnosed abroad; 26 of the 28 cases were followed up for a period of two to 12 months , a mean of 6.9 months , with no evidence of neoplasia . This group could not be included in our incidence data since their lesions were not verified by material evidence as was the case in our material.

27. Accordingly , our estimated figures may represent minimal rather than actual incidence rates of CIN in this population of females . Increased risk of CIN is reported in females with certain sexual characteristics exemplified by early starting age and multiple sex partners. Current evidence points to HPV subtypes as the most important single factor in the etiology of cervical neoplasia but one report understimates its role .

28. A previous study in Jordanian females suggested little role of sexually transmitted disease in pelvic inflammatory disease, but this does not exclude the role of HPV in the pathogenesis of CIN. Table 1 demonstrates a similar pattern of CIN grades in the two groups but in group 2 , lower CIN grades were more frequent, suggesting better health awareness in this latter group. Further study is desired to demonstrate the etiology of cervical intraepithelial neoplasia and the role of HPV in this population. .

29. Maternal and child health clinics serving lower socioeconomic groups should activate screening programs to discover earlier stages of cervical neoplasia . CIN was reported to be potentiated by HIV ( human immunodeficiency virus ) infection and , in contrast to our findings , the contraceptive pill . Increased risk of CIN was always reported in prisoners . Although one study reported parity to exert independent influence on the risk of CIN , ²¹ our study and others could not confirm this finding .

30. Circumcision in male partners and marital status were associated with lower frequency of CIN, which are believed circumstantial and not due to direct influence . Age at and duration of marriage, breast feeding, menstrual disorders and socioeconomic class had no relationship to the frequency of CIN in our patients . Follow – up was possible in a minority of patients . Such difficulties with follow–up are often encountered in developing countries, which interferes with an authentic study of the natural history and outcome of cervical neoplasia.

31. Among different treatment methods of CIN advocated, cautery and cone biopsy proved effective in our patients with CIN as indicated by clear Pap smears at 30.3 month’s average follow – up . Colposcopy was not available in Jordan during the time of this study , nor was loop diathermy On the other hand , three females developed CIN over a 25–month average follow–up, endorsing the value of repeating Pap smears at regular intervals in our population.

32. It is to conclude that in Jordanian females over 30 years of age, CIN is a lesion worth looking for annually in obstetrics and gynecology clinics . It remains to be seen whether this applies to general practice , since the incidence of CIN in the general population of Jordanian females remains to be determined .