Journal List > J Gynecol Oncol > v.29(4) > 1108770

Tai, Chen, Hsu, Chiang, You, Chen, and Cheng: Risks of cervical intraepithelial neoplasia grade 3 or invasive cancers in ASCUS women with different management: a population-based cohort study

Abstract

Objective

To investigate the progression risk of atypical squamous cells of undetermined significance (ASCUS) with different clinical managements.

Methods

Women with their first diagnosis of ASCUS cytology were retrieved from the national cervical cancer screening database and linked to the national health insurance research database to identify the management of these women. The incidences of developing cervical intraepithelial neoplasia grade 3 and invasive cervical cancer (CIN3+) were calculated, and the hazard ratios (HRs) were estimated using a Cox proportional hazards model. This study was approved by the Research Ethics Committee of the National Taiwan University Hospital and is registered at ClinicalTrials.gov (Identifier: NCT02063152).

Results

There were total 69,741 women included. Various management strategies including colposcopy, cervical biopsies and/or endocervical curettage, and cryotherapy, failed to reduce the risk of subsequent CIN3+ compared with repeat cervical smears. Loop electrosurgical excision procedure/conization significantly decreased risk of subsequent CIN3+ lesions (HR=0.22; 95% confidence interval [CI]=0.07–0.68; p=0.010). Women in their 40s–50s had an approximately 30% risk reduction compared to other age groups. Women with a previous screening history >5 years from the present ASCUS diagnosis were at increased risk for CIN3+ (HR=1.24; 95% CI=1.03–1.49; p=0.020).

Conclusion

In women of first-time ASCUS cytology, a program of repeat cytology can be an acceptable clinical option in low-resource settings. Caution should be taken especially in women with remote cervical screening history more than 5 years.

References

1. Papanicolaou GN, Traut HF. Diagnosis of uterine cancer by the vaginal smear. New York, NY: Commonwealth Fund;1943.
2. Ayre JE. Selective cytologic smear for the diagnosis of cancer. Am J Obstet Gynecol. 1947; 53:609–17.
3. Gagnon F. Contribution to the study of the etiology and prevention of cancer of the cervix of the uterus. Am J Obstet Gynecol. 1950; 60:516–22.
crossref
4. Chen YY, You SL, Chen CA, Shih LY, Koong SL, Chao KY, et al. Effectiveness of national cervical cancer screening programme in Taiwan: 12-year experiences. Br J Cancer. 2009; 101:174–7.
crossref
5. Davey DD, Neal MH, Wilbur DC, Colgan TJ, Styer PE, Mody DR. Bethesda 2001 implementation and reporting rates: 2003 practices of participants in the College of American Pathologists Interlaboratory Comparison Program in Cervicovaginal Cytology. Arch Pathol Lab Med. 2004; 128:1224–9.
crossref
6. Solomon D, Davey D, Kurman R, Moriarty A, O'Connor D, Prey M, et al. The 2001 Bethesda System: terminology for reporting results of cervical cytology. JAMA. 2002; 287:2114–9.
crossref
7. Bulten J, de Wilde PC, Boonstra H, Gemmink JH, Hanselaar AG. Proliferation in “atypical” atrophic Pap smears. Gynecol Oncol. 2000; 79:225–9.
crossref
8. Saminathan T, Lahoti C, Kannan V, Kline TS. Postmenopausal squamous-cell atypias: a diagnostic challenge. Diagn Cytopathol. 1994; 11:226–30.
crossref
9. Solomon D, Schiffman M. Tarone RALTS Study group. Comparison of three management strategies for patients with atypical squamous cells of undetermined significance: baseline results from a randomized trial. J Natl Cancer Inst. 2001; 93:293–9.
crossref
10. ASCUS-LSIL Triage Study (ALTS) Group. Results of a randomized trial on the management of cytology interpretations of atypical squamous cells of undetermined significance. Am J Obstet Gynecol. 2003; 188:1383–92.
11. Siebers AG, Arbyn M, Melchers WJ, van Kemenade FJ, Vedder JE, van der Linden H, et al. Effectiveness of two strategies to follow-up ASC-US and LSIL screening results in the Netherlands using repeat cytology with or without additional hrHPV testing: a retrospective cohort study. Cancer Causes Control. 2014; 25:1141–9.
crossref
12. Wen CP, Tsai SP, Chung WS. A 10-year experience with universal health insurance in Taiwan: measuring changes in health and health disparity. Ann Intern Med. 2008; 148:258–67.
crossref
13. Lu TH, Lee MC, Chou MC. Accuracy of cause-of-death coding in Taiwan: types of miscoding and effects on mortality statistics. Int J Epidemiol. 2000; 29:336–43.
crossref
14. Cheng WF, Huang CY, You SL, Chen CJ, Hu CH, Chen CA. Clinical significance of cytologic atypical squamous cells of undetermined significance. Obstet Gynecol. 2009; 113:888–94.
crossref
15. Ostör AG. Natural history of cervical intraepithelial neoplasia: a critical review. Int J Gynecol Pathol. 1993; 12:186–92.
16. Winer RL, Hughes JP, Feng Q, Xi LF, Cherne S, O'Reilly S, et al. Early natural history of incident, type-specific human papillomavirus infections in newly sexually active young women. Cancer Epidemiol Biomarkers Prev. 2011; 20:699–707.
crossref
17. Ho GY, Bierman R, Beardsley L, Chang CJ, Burk RD. Natural history of cervicovaginal papillomavirus infection in young women. N Engl J Med. 1998; 338:423–8.
crossref
18. Holowaty P, Miller AB, Rohan T, To T. Natural history of dysplasia of the uterine cervix. J Natl Cancer Inst. 1999; 91:252–8.
crossref
19. Sauvaget C, Muwonge R, Sankaranarayanan R. Meta-analysis of the effectiveness of cryotherapy in the treatment of cervical intraepithelial neoplasia. Int J Gynaecol Obstet. 2013; 120:218–23.
crossref
20. Chumworathayi B, Thinkhamrop J, Blumenthal PD, Thinkhamrop B, Pientong C, Ekalaksananan T. Cryotherapy for HPV clearance in women with biopsy-confirmed cervical low-grade squamous intraepithelial lesions. Int J Gynaecol Obstet. 2010; 108:119–22.
crossref
21. Poomtavorn Y, Suwannarurk K, Thaweekul Y, Maireang K. Diagnostic value of endocervical curettage for detecting dysplastic lesions in women with atypical squamous cells of undetermined significance (ASC-US) and low grade squamous intraepithelial lesion (LSIL) Papanicolaou smears. Asian Pac J Cancer Prev. 2014; 15:3461–4.
crossref
22. Jakobsson M, Gissler M, Paavonen J, Tapper AM. Loop electrosurgical excision procedure and the risk for preterm birth. Obstet Gynecol. 2009; 114:504–10.
crossref
23. Bevis KS, Biggio JR. Cervical conization and the risk of preterm delivery. Am J Obstet Gynecol. 2011; 205:19–27.
crossref
24. de Sanjosé S, Diaz M, Castellsagué X, Clifford G, Bruni L, Muñoz N, et al. Worldwide prevalence and genotype distribution of cervical human papillomavirus DNA in women with normal cytology: a meta-analysis. Lancet Infect Dis. 2007; 7:453–9.
crossref
25. Chiang YC, Cheng WF, Chen YL, Chang MC, Hsieh CY, Lin MC, et al. High-risk human papillomavirus, other than type 16/18, in predominantly older Taiwanese women with high-grade cervical preinvasive lesions. Taiwan J Obstet Gynecol. 2013; 52:222–6.
crossref
26. Hammer A, Mejlgaard E, Gravitt P, Høgdall E, Christiansen P, Steiniche T, et al. HPV genotype distribution in older Danish women undergoing surgery due to cervical cancer. Acta Obstet Gynecol Scand. 2015; 94:1262–8.
crossref
27. Chen CA, Liu CY, Chou HH, Chou CY, Ho CM, Twu NF, et al. The distribution and differential risks of human papillomavirus genotypes in cervical preinvasive lesions: a Taiwan Cooperative Oncologic Group Study. Int J Gynecol Cancer. 2006; 16:1801–8.
crossref
28. Bentley JSociety of Canadian Colposcopists. Colposcopic management of abnormal cervical cytology and histology. J Obstet Gynaecol Can. 2012; 34:1188–202.
29. Massad LS, Einstein MH, Huh WK, Katki HA, Kinney WK, Schiffman M, et al. 2012 updated consensus guidelines for the management of abnormal cervical cancer screening tests and cancer precursors. J Low Genit Tract Dis. 2013; 17:S1–27.
crossref
30. Manos MM, Kinney WK, Hurley LB, Sherman ME, Shieh-Ngai J, Kurman RJ, et al. Identifying women with cervical neoplasia: using human papillomavirus DNA testing for equivocal Papnicolaou results. JAMA. 1999; 281:1605–10.

Fig. 1.
Flow of the study population among all women who attended cervical cancer screening with ASCUS cytology during 2004–2007. ASCUS, atypical squamous cells of undetermined significance; CIN3+, cervical intraepithelial neoplasia grade 3 and invasive cervical cancer; ECC, endocervical curettage; LEEP, loop electrosurgical excision procedure.
jgo-29-e55f1.tif
Fig. 2.
Survival analysis of subsequent risk for CIN3+ diagnosis in 69,741 women with ASCUS cytology according to management. X-axis refers to follow-up time in months since 1 year after the ASCUS cytology. Y-axis refers to cumulative incidence of subsequent CIN3+. ASCUS, atypical squamous cells of undetermined significance; CIN3+, cervical intraepithelial neoplasia grade 3 and invasive cervical cancer; ECC, endocervical curettage; LEEP, loop electrosurgical excision procedure.
jgo-29-e55f2.tif
Table 1.
Baseline characteristics of 69,741 women with ASCUS cytology according to age distribution, screening interval, educational status, management, and incidence of subsequent CIN3+
Characteristics No. of ASCUS patients Person-years of follow-up No. of CIN3 No. of invasive cancer No. of p CIN3+ Incidence of CIN3+ per 100,000 person-years*
Total 69,741 266,011 669 103 772 290.2
Age (yr)            
 20–29 6,136 24,263 71 3 74 305.0
 30–39 19,193 73,320 227 29 256 349.2
 40–49 22,448 85,621 179 42 221 258.1
 50–59 13,999 52,798 100 19 119 225.4
 60–69 5,423 20,580 68 5 73 354.7
 >70 2,542 9,429 24 5 29 307.6
Previous screening interval (yr)            
 <1 15,368 60,333 105 22 127 210.5
 1–3 31,505 118,413 307 23 330 278.7
 3–5 7,927 29,703 84 23 107 360.2
 >5 or never 14,941 57,562 173 35 208 361.3
Educational status            
 <6 years of schooling 15,210 58,696 146 28 174 296.4
 Junior high school 11,923 45,686 115 19 134 293.3
 Senior high school 24,541 93,593 242 45 287 306.6
 College or graduate school 17,412 65,567 165 11 176 268.4
Management            
 No management 18,028 68,557 198 59 257 374.9
Non-interventional procedures            
 Repeated Pap smear 26,000 99,659 232 27 259 259.9
 Colposcopy 3,841 14,208 28 4 32 225.2
 Cervical biopsy and/or ECC 15,535 58,765 172 6 178 302.9
Interventional procedures            
 Cryotherapy 5,210 20,267 36 7 43 212.2
 LEEP/conization 1,127 4,555 3 0 3 65.9

Data are number (%) unless otherwise specified.

ASCUS, atypical squamous cells of undetermined significance; CIN3, cervical intraepithelial neoplasia grade 3; CIN3+, cervical intraepithelial neoplasia grade 3 and invasive cervical cancer; ECC, endocervical curettage; LEEP, loop electrosurgical excision procedure.

* Age-adjusted incidence rate of CIN3+ per 100,000 person-years.

Table 2.
Multivariate analysis of the risk of subsequent CIN3+ lesion in 69,741 women with ASCUS cytology
Variables HR 95% CI of HR p
Age (yr)      
 20–29 0.77 0.59–1.00 0.060
 30–39 1.00    
 40–49 0.73 0.60–0.88 <0.001
 50–59 0.61 0.48–0.78 <0.001
 60–69 0.90 0.66–1.23 0.500
 >70 0.72 0.47–1.11 0.140
Previous screening interval (yr)      
 <1 0.77 0.62–0.94 0.010
 1–3 1.00    
 3–5 1.25 1.00–1.55 0.050
 >5 or never 1.24 1.03–1.49 0.020
Educational status      
 <6 years of schooling 1.00    
 Junior high school 0.98 0.76–1.26 0.860
 Senior high school 0.96 0.75–1.22 0.720
 College or graduate school 0.80 0.61–1.04 0.100
Management      
 No management 1.39 1.17–1.66 <0.001
 Non-interventional procedures      
 Repeated Pap smear 1.00    
 Colposcopy 0.80 0.55–1.16 0.240
 Cervical biopsy and/or ECC 1.05 0.87–1.28 0.590
Interventional procedures      
 Cryotherapy 0.76 0.55–1.05 0.100
 LEEP/conization 0.22 0.07–0.68 0.010

ASCUS, atypical squamous cells of undetermined significance; CI, confidence interval; CIN3+, cervical intraepithelial neoplasia grade 3 and invasive cervical cancer; ECC, endocervical curettage; HR, hazard ratio; LEEP, loop electrosurgical excision procedure.

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