From August 2018 to April 2019, 100,000 screening Pap smears were collected in Isfahan, Iran, from which, 75 Pap smears had AGCs with a prevalence rate of 0.075%. Five women were excluded from the study due to excluding criteria, leaving 70 patients.
The mean of age and marriage age in studied women were 43.1 and 18.8 years, respectively. Most of the women (81.4%) were Multiparous. In these women, 15.7% had histories of abortion and 8.6% were active or passive smokers. Menopause had occurred in 20% and 37.6% reported histories of STD.
Comparison of patients’ characteristics in regard to colposcopy findings are presented in Table 1. The mean age, marriage age and gravidity were similar among women with normal, benign and malignant colposcopy (P>0.05). Parity status, history of abortion, the patients’ and their partners’ smoking status, history of STD and menopause status in women with normal, benign and malignant colposcopy were similar and no significant differences were noted (P>0.05). In addition, education level, SES and contraceptive usage were not significantly different among women in regard to their colposcopy findings (P>0.05).
Comparison of women’s characteristics in regard to ECC findings are shown in Table 2. Women’s age, marriage age and gravidity were similar in regard to benign or malignant ECC findings (P>0.05). Also, women with benign or malignant ECC findings were similar in respect to all other variables including parity status, history of abortion, smoking status, education level, SES, history of STD, menopause status and contraceptive usage (P>0.05).
Table 3 shows the comparison between women’s characteristics in regard to EMC findings. Women with malignant results were significantly older than other women with normal and benign EMC findings (P=0.039). Mean marriage age and gravidity were similar among women with normal, benign and malignant EMC (P>0.05). Menopause had occurred in 71.4% of women with malignant, whereas, only 14.9% of women with normal findings had experienced menopause (P=0.003). All the other studied charact-eristics were similar among women in regard to EMC findings (P>0.05).
Repetitive Pap smear tests at baseline were normal in 15.7% of the women, 77.2% had inflammation, 4% had AGCs and 3.1% had necrosis. According to colposcopy findings, 61.2%, 7.5%, and 31.3% of pati-ents had normal, benign and premalignant or malignant findings, respectively. Our results showed the 100% sensitivity and 72.4% specificity of colposcopy for cervical pathologic lesions but only 60% sensitivity and 43% specificity of colposcopy for endometrial pathologic lesions. ECC findings in 95.5% of women was indicative of benign lesions and malignant lesions in 4.5%. Moreover, findings of EMC in studied women were as follows: 79.7% with normal, 8.5% with benign and 11.9% with malignant lesions. Pap smears with several AGCs were associated with benign lesions in 24.2% of the cases and premalignant and malignant lesions in 14.2% of the cases.
Of these 70 patients, five patients underwent surgery because of cervical or endometrial malignant lesions. Four of them received medical therapy due to diagnosis of endometrial hyperplasia. Surgery or medical therapy was not reported in 60 patients. One patient received chemo radiation therapy because she was inappropriate candidates for surgery due to stage 2B of cervical cancer.
During the six-month follow-up period, except five women who underwent hysterectomy and one patient who passed away, 24.6% of fallow-up Pap tests were normal and 75.4% had inflammation.
Table 4 shows abnormal ECC and EMC findings in studied women with AGC Pap smears and the relative outcomes.

Table 1. Profile of studied women by colposcopy findings

Data are mean ± SD, median [IQR] or number (%), STD: Sexually Transmitted Diseases
 
Table 2. Profile of studied women by Endocervical curettage findings

Data are mean ± SD, median [IQR] or number (%), STD: Sexually Transmitted Diseases
 
Table 3. Profile of studied women by Endometrial curettage findings

Data are mean ± SD, median [IQR] or number (%), STD: Sexually Transmitted Diseases
 
Table 4. Endocervical curettage (ECC) and Endometrial curettage (EMC) findings in studied women and our outcomes

According to the literature, AGCs are rarely found in Pap smears (<5%) (13, 14), while malignant or premalignant lesions can be found in 22% to 53% samples with AGCs (15). AGCs observation rate in the present study (0.075%) was almost the same as the pervious literature. Furthermore, in our study, 38% of pathologic lesions including 24.2% benign lesion and 14.2% malignant or premalignant lesions were diag-nosed in patients with AGCs in their Pap smears.
In a study by Wanq et al. (2016) on 3054328 Pap smears from 1980 to 2011, the prevalence of cervical cancer was 1.4% in women with AGC, which was lower than that of women with high grade squamous intraepithelial lesion (HSIL) (2.5%), but higher than that of women with low grade squamous intraepithelial lesion (LSIL) (0.2%). Cervical adenocarcinoma was the most common malignancy in patients with AGCs in this study. The incidence rate of adenocarcinoma was 61 times higher in women with normal cytology results in the first screening round after AGC, and remained nine times higher for up to 15.5 years (16). In our study, histologic findings revealed cervical squamous cell carcinoma in two patients. Cervical adenocarcinoma and endometrial adenocarcinoma were separately diagnosed in two patients (4% had cervical cancer and 1.3% had endometrial cancer).
In a study by Saad RS et al. (2006) on 90 women with AGC Pap smears, 40% assertion with important pathologic lesions was reported, especially in patients older than 50 (17). In a Kim MK et al. (2017) study on 435778 Pap smears, 0.17% AGC cytology was reported. In patients with malignant pathology AGC-NOS, AEM and AEC were reported in 15.3%, 59.6% and 25.1% of the cases, respectively. Prevalence of endometrial neoplasia in women over 40 years and prevalence of cervical neoplasia in women under 40 years were discovered (18). In a Pradham et al. (2016) study on 589830 Pap smears, 0.06% AGC cytology was reported. The underling neoplasia in patients under and over 50 years were CIN2-3 and endometrial carcinoma, respectively (19). We understood that endometrial pathologic lesions but not cervical lesions in older and post-menopausal women were the most common in our study.
The consistency between cytological findings and colposcopic and histopathological findings is evaluated in other studies. In a study by Akhter et al., the alignment between colposcopic findings, Pap smear cytology and histopathological diagnosis in gynecology patients was assessed. They reported a significant association between colposcopic findings and histopathological diagnosis and weak consistency between cytological findings and colposcopic and histopathological findings (20). Dasari et al. found that histopathology findings were not in agreement with cytological findings and showed high proportion of CIN, which can be found in Pap smear with persistent inflammatory (21). Furt-hermore, other studies reported insignificant association between cytology and colposcopic findings. The consistency between cytology and histopathology was fair (22, 23). In our study on Pap smears with AGCs, we realized that although colposcopy was neither specific nor sensitive for endometrial pathologic lesions in patients with AGC Pap smears indicating the necessity of endometrial biopsy for these patients, sensitivity and specificity of colposcopy for cervical pathologic lesions were 100% and 72.4%, respectively, which confirms the critical role of colposcopy in early diagnosis of pathologic cervical lesions in women with AGC Pap smears.
This study has limitations and the results should be interpreted with caution. Firstly, due to the small samples size and consequently, low percentage of women with AGC Pap tests, we were not able to analyze the colposcopy, ECC and EMC findings in women with AGC in their Pap smears by classifying them into sub categories. Secondly, women who underwent health examinations at governmental gynecology clinics were enrolled on this study; therefore, our results may not reflect the general population. Hence, further multi-center studies with lager sample sizes are warranted to compare the colposcopy, ECC and EMC findings in women with AGC Pop smears.
 

According to our study and the similar studies, Pap smear screening in asymptomatic women is very important in order to prevent mortality. Moreover, because of high association between AGC cytology and pathologic cervical and endometrial lesions, intensive assessment is necessary in women with AGC Pap smears, especially in older and post-menopausal women in order to reduce mortality. We also conclude that colposcopy is a sensitive and specific diagnostic method for cervical pathology, but not for endometrial pathology, in women with AGC Pap smears. We are pleased to contribute to access the best diagnostic and therapeutic approach for cervical cancer in women by presenting this study and reviewing other similar studies.

 

Statement of Ethics

The patient had ssigned the informed consent in the aim of reporting present article.

 

We would like to thank all the researchers and care providers for early detection and treatment of gynecological cancers to prevent mortality and morbidity of women in the worldwide. This cross-sectional study has been approved and implemented in the Department of Obstetrics and Gynecology of Isfahan University of Medical Sciences.

 

The authors declared no conflicts of interest.