Management of ASCUS findings in Papanicolaou smears. A retrospective study

Aim: Atypical squamous cells of undetermined significance (ASCUS) are a cervical cytologic finding category suggestive but not definitive of squamous intraepithelial lesions. ASCUS remains an incompletely described entity and accounts for even 5%-10% of reported Papanicolaou (Pap) smears. The management of women with such cytologic findings remains controversial. The aim of this study was to evaluate the cytology laboratory findings with regards to ASCUS diagnosis, using cervical Pap smears, and colposcopic biopsies, as well as their management. Materials and Methods: This is a retrospective study of patients with ASCUS Pap smears taken during the period January 2010 December 2010 in the Second Department of Obstetrics and Gynecology, Aretaieion Hospital. Results: During the study period, 657 Pap smears were examined at the Aretaieion Hospital; moreover, seven patients, whose Pap smears were cytologically diagnosed with ASCUS, were referred from other clinics, providing a total of 42 cases with a descriptive diagnosis of ASCUS for review. Of the 42 cases, eight were not studied because they were either lost in follow-up or they did not have available data. The remaining 34/42 patients were evaluated by colposcopic examination and directed biopsies where necessary. The ratio of ASCUS to low-grade squamous intraepithelial lesion (LGSIL), high-grade squamous cell intraepithelial lesion (HGSIL) or squamous cell carcinoma (SCC) was 5/34, 1/34, and 0/34, respectively. In the 34 ASCUS cases evaluated by colposcopy, the age distribution varied from 22 to 54 years. Eight of 34 cases did not have a child, 7/34 were primigravida, 18/34 were secondigravida, and 1/34 had four children. Four out of 34 cases were postmenopausal, 3/34 referred no history of abnormal bleeding, 21/34 were smokers, 6/34 used oral contraceptives, 2/34 used intrauterine devices, 1/34 took replacement of hormones, 4/34 had prior abnormal Pap smears human papillomavirus (HPV), or 1/34 had previous cancer (breast cancer). Colposcopy was inconclusive in 4/34 patients, while 8/34 cases were negative for Schiller and acetic acid tests and also had normal colposcopy. Infectious organisms were found in 8/34 patients with ASCUS, including actinomyces (1/8), trichomonas (5/8), and candida albicans (2/8). Histologic tests revealed 16/34 koilocytosis cases, 5/34 LGSIL, 1/34 HGSIL, and 0/34 SCC. Conclusion: The dilemma in the management of patients with an ASCUS diagnosis still exists as a significant problem for clinicians

ASCUS; Papanicolaou smear; Colposcopy; Management

[1] Nuovo G.J., Walsh L.L., Gentile J.L., Blanco J.S., Koulos J., Heimann A.: “Correlation of the Papanicolaou smear and human papillomavirus type in women with biopsy-proven cervical squamous intraepithelial lesions”. Am. J. Clin. Pathol., 1991, 96, 544.

[2] Bosch F.X., Manos M.M., Munoz N. et al.: “Prevalence of human papillomavirus in cervical cancer: a worldwide perspective”. J. Natl. Cancer Inst., 1995, 87, 796.

[3] Schiffman M., Herrero R., Hildesheim A. et al.: “HPV DNA testing in cervical cancer screening: results from women in a high risk province in Costa Rica”. JAMA, 2000, 283, 87.

[4] Wright T.C. jr, Massad S., Dunton C.J., Spitzer M., Wilkinson E.J., Solomon D.: “2006 Consensus guidelines for the management of women with abnormal cervical cancer screenibg tests”. Am. J. Obstet. Gynecol., 2007, 197, 346.

[5] Chan P.K., Mak K.H., Cheung J.L.K.: “Genotype spectrum of cervical human papillomavirus infection among sexually transmitted disease clinic patients in Hong Kong”. J. Med. Virol., 2001, 68, 273.

[6] Schelecht N.F., Kulaga S., Robitaille J.: “Persistent human papillomavirus infection as a predictor of cervical intraepithelial neoplasia”. JAMA, 2001, 286, 3106.

[7] Coxx J.T., Lorincz A.T., Schiffman M.H., Sherman M.E., Cullen A., Kurman R.J.: “Human papillomavirus testing by hybrid capture appears to be useful in triaging women with a cytologic diagnosis of atypical squamous cells of undetermined significance”. Am. J. Obstet. Gynecol., 1995, 172, 946.

[8] Kinney W.K., Manos M.M., Hurley L.B., Ransley J.E.: “Where’s the high grade cervical neoplasia? The importance of minimally abnormal Papanicolaou diagnoses”. Obstet. Gynecol., 1998, 91, 973.

[9] Prendiville W., Ritter J., Tatti S., Twiggs L.: “Management del Pap test anormale. Linee guida della SICPCV”. In: “Colposcopy: management options”. Milano, Elsevier Italia, 2005, 205.

[10] Kurman R.J., Henson D.E., Herbst A.L., Noller K.L., Schiffman M.H.: “Interim guidelines for management of abnormal cervical cytology”. J. Am. Med. Assoc., 1994, 271, 1866.

[11] Selvaggi S., Haefner H.: “Reprorting of atypical squamous cells of undetermined significance on cervical smears: is it significant?”. Diagn. Cytopathol., 1995, 13, 352.

[12] Taylor R., Guerrieri J., Nash J., Henry M., O’Connor D.: “Atypical cervical cytology colposcopic follow-up using the Bethesda system”. J. Reprod. Med., 1993, 38, 443.

[13] Kim J.J., Wright Jr. T.C., Goldie S.J.: “Cost-effectiveness of alternative triage strategies for atypical squamous cells of undetermined significance”. JAMA, 2002, 287, 2382.

[14] ASCUS-LSIL, Traige Study (ALTS) Group. Results of arandomized trial on the management of cytology interpretations of atypical squamous cells of undetermined significance. Am. J. Obstet Gynecol., 2003, 188, 1383.

[15] Spinillo A., Dal Bello B., Gardella B., Roccio M., Dacco M.D., Silini E.M.: “Multiple human papillomavirus infection and high grade cervical intraepithelial neoplasia amomg women with cytological diagnosis of atypical squamous cells of undetermined significance of low grade squamous intraepithelial lesions”. Gynecol. Oncol., 2009, 113, 115, Epub 2009 Jan. 31.

[16] Nasiell K., Roger V., Nsiell M.: “Behavior of mild cervical dysplasia during long-term follow-up”. Obstet. Gynecol., 1986, 61, 609.

[17] Hall S., Wu T.C., Soudi N., Sherman M.E.: “Low grade squamous intraepithelial lesions: cytologic predictors of biopsy confirmation”. Diagn. Cytopathol., 1994, 10, 3.

[18] Williams M.L., Rimm D.L., Pedigo M.A., Frable W.J.: “Atypical squamous cells of undetermined significance: correlative histologic an follow-up studies from an academic medical centre”. Diagn. Cytopathol., 1997, 16, 1.

[19] Reiter Rc.: “Management of initial atypical cervical cytology: a randomized prospective study”. Obstet. Gynecol., 1986, 68, 237.

[20] Davey D.D., Naryshkin S., Nielsen M.L., Kline T.S.: “Atypical squamous cells of undetermined significance: interlaboratory comparison and quality assurance monitors”. Diagn. Cytopathol., 1994, 11, 390.

[21] Kline M.J., Davey D.D.: “Atypical squamous cells og undetermined significance qualified: a follow-up study”. Diagn. Cytopathol., 1996, 14, 380.

[22] Howell L.P., Davis R.L.: “Follow-up of Papanicolaou smears diagnosed as atypical squamous cells of undetermined significance”. Diagn. Cytopathol., 1996, 14, 20.

[23] Slawson D.C., Bennet J.H., Simon L.J., Herman J.M.: “Should all women with cervical atypia be referred for colposcopy: a Harnet Stufy. Harrisburgh Area Research Network”. J. Fam. Pract., 1994, 38, 387.

[24] Gordon P., Hatch K.: “Survey of colposcopy practices by obstetricians and cynecologists”. J. Reprod. Med., 1992, 37, 861.

[25] Titus K.: “HPV test: antidote to ASCUS headache?”. CAP Today, 1996, 10, 52.

[26] Quddus M.R., Neves T., Reilly M.E., Steinhoff M.M., Sung C.J.: “Does the ThinPrep Imaging System increase the detection of high-risk HPV-positive ASC-US and AGUS? The women and infants Hospital experience with over 200,000 cervical cytology cases”. Cytojournal, 2009, 6, 15.

[27] Rader A.E., Rose P.G., Rodriguez M., Mansbacher S., Pitlik D., Abdul Karim F.W.: “Atypical squamous cells of undetermined significance in women over 55. Comparison with the general population and implications for management”. Acta Cytol., 1999, 43, 357.

[28] Lee K.R., Ashfaq R., Birdsong G.G., Corkill M.E., MxIntosh K.M., Inhorn S.L.: “Comparison of conventional Papanicolaou smears and a fluid-based, thin-layer system for cervical cancer screening”. Obstet. Gynecol., 1997, 90, 278.

[29] Sherman M.E., Schiffman M., Cox T.: “Effects of age and human viral load on colposcopy triage: data from the randomized atypical squamous cells of undetermined significance low/ low-grade squamous intraepithelial lesions triage study (ALTS)”. J. Natl. Cancer Ins., 2002, 94, 102.

[30] Yang M., Path M.R.C., Zachariah S.: “ASCUS on cervical cytologic smears: clinical significance”. J. Reprod. Med., 1997, 42, 329.

[31] Sheils L.A., Wilbur D.C.: “Atypical squamous cells of undetermined significance: stratification of the risk of association with, or progression to, squamous intraepithelial lesions based on morphologic subcategorization”. Acta Cytol., 1997, 41, 1065.

[32] Hempling R.E.: “Preinvasive lesions of the cervix: Diagnosis and management”. In: Piver M.S. (ed.): “Handbook of Gynecologic Oncology”, 2nd and. Boston: Little Brown Handbooks 1996, 92.

[33] Ergeneli M.h., Duran E.H., Ergin T., Demirhan B., Erdogaan M.: “Atypical squamous cells of undetermined significance clinical experience in a Turkish University Hospital”. Eur. J. Obstet. Gynecol., 2001, 96, 108.

[34] Gerber S., De Grandi P., Petignat P., Mihaescu A., Delaloye J.F.: “Colposcopic evaluation after a repeat atypical squamous cells of undetermined significance (ASCUS) smear”. Int. J. Gynecol. Obstet., 2001, 75, 251.

[35] Chichareon S.B., Tocharoenvanich S.T.: “Situation analysis of atypical squamous cells of undetermined significance smears in Songklanagarind Hospital”. J. Obstet. Gynaecol. Res., 2001, 28, 269.

[36] Lonky N.M., Felix J.C., Naidu Y.M., Wolde-Tsadik G.: “Triage of atypical squamous cells of undetermined significance with hybrid capture II. Colposcopy and histologic papillomavirus correlation”. Obstet. Gynecol., 2003, 101, 481.

[37] Manos M.M., Kinney W.K., Hurley L.B. et al.: “Identifying women with cervical neoplasia: using human papillomavirus DNA testing for equivocal Papanicolaou results”. JAMA, 1999, 281, 1605.

[38] Solomon D., Stoler M., Jeronimo J., Khan M., Castle P., Schiffman M.: “Diagnostic utility of endocervical curettage in women undergoing colposcopy for equivocal or low-grade cytologic abnormalities”. Obstet. Gynecol., 2007, 110, 288.