Interpreting a Diagnosis of Atypical Squamous Cells of Undetermined Significance in Cervical Cytology and its Association with Human Papillomavirus: A retrospective analysis of 180 cases in Kuwait

Kusum Kapila 1, Meera Balakrishnan 2, Rola H Ali 1, Ahlam Al-Juwaiser 2, Sara S George 1, Mrinmay K Mallik 2

Affiliations

01 November 2020

-

doi: 10.18295/squmj.2020.20.04.007

Abstract

Objectives: Atypical squamous cells of undetermined significance (ASC-US) represent a diagnostic challenge during cervical cytology. This study aimed to review and identify high-risk human papillomavirus (HR-HPV) genotypes among previously diagnosed ASC-US cases in Kuwait.

Methods: This retrospective study analysed 180 cases diagnosed as ASC-US between June 2017 and May 2018 at the Mubarak Al-Kabeer Hospital, Kuwait. Cervical specimens were assayed to determine the presence of HR-HPV DNA; subsequently, positive cases underwent genotyping and were categorised into three groups (HPV 16, HPV 18/45 and other HR-HPV types).

Results: In total, ASC-US was confirmed in only 105 cases (58.3%), with the remaining cases reclassified as negative for intraepithelial lesions or malignancy (NILM; 32.2%) and epithelial cell abnormalities (ECA; 9.4%). Of these, HR-HPV DNA was present in 20 ASC-US (19%), one NILM (1.7%) and six ECA (35.3%) cases. There were 62 Kuwaiti and 43 non-Kuwaiti women with confirmed ASC-US; of these, three (4.8%), six (9.7%) and four (6.5%) Kuwaitis and one (2.3%), one (2.3%) and five (11.6%) non-Kuwaitis had HPV 16, both HPV 16 and 18/45 and other HR-HPV genotypes, respectively. Of those with HR-HPV DNA, the NILM case had the HPV 18/45 genotype, while the six ECA cases had the HPV 16 (n = 1), both HPV 16 and 18/45 (n = 1) and other HR-HPV (n = 4) genotypes.

Conclusion: Overall, HR-HPV DNA was present in 19% of ASC-US cases compared to 1.7% of NILM cases initially misdiagnosed as ASC-US. Re-review of cervical cytology diagnoses may reduce unnecessary costs associated with HR-HPV genotyping.

Keywords: Atypical Squamous Cells of Undetermined Significance; Cervical Smears; Cytological Techniques; Human Papilloma Virus; Kuwait; Papanicolaou Test.

Conflict of interest statement

CONFLICT OF INTEREST The authors declare no conflicts of interest.

Similar articles

Impact of high-risk Human Papillomavirus genotyping in cervical disease in the Northern region of Portugal: Real-world data from regional cervical cancer screening program.

Rosário A, Sousa A, Marinho-Dias J, Medeiros R, Lobo C, Leça L, Coimbra N, Tavares F, Baldaque I, Martins G, Monteiro P, Henrique R, Sousa H.J Med Virol. 2023 Jan;95(1):e28414. doi: 10.1002/jmv.28414.PMID: 36541747

Validation of HPV triage in cytology-based cervical cancer screening for ASC-US cases using Japanese data.

Aoki ES, Saika K, Kiguchi K, Morisada T, Aoki D.J Gynecol Oncol. 2023 Mar;34(2):e14. doi: 10.3802/jgo.2023.34.e14. Epub 2022 Nov 18.PMID: 36424706 Free PMC article.

Silent High Grade Cervical Intraepithelial Neoplasia in Atypical Smears from Liquid Based Cervical Cytology - Three Years Experience in Thammasat University Hospital.

Lertvutivivat S, Chanthasenanont A, Chanthasenanont A, Muangto T, Nanthakomon T, Pongrojpaw D, Bhamarapravatana K, Suwannarurk K.Asian Pac J Cancer Prev. 2016;17(9):4353-4356.PMID: 27797243

[Evaluation of CIN2+ /CIN3+ risk of different HPV subtypes infection combined with abnormal cytology status].

Luo HX, Du H, Liu ZH, Zhang LJ, Wang C, Wu RF.Zhonghua Zhong Liu Za Zhi. 2018 Mar 23;40(3):232-238. doi: 10.3760/cma.j.issn.0253-3766.2018.03.015.PMID: 29575846 Chinese.

Human papillomavirus persistence or clearance after infection in reproductive age. What is the status? Review of the literature and new data of a vaginal gel containing silicate dioxide, citric acid, and selenite.

Huber J, Mueller A, Sailer M, Regidor PA.Womens Health (Lond). 2021 Jan-Dec;17:17455065211020702. doi: 10.1177/17455065211020702.PMID: 34096424 Free PMC article. Review.

Cited by

Willingness to get HPV vaccination among female university students in Kuwait and its relation to vaccine conspiracy beliefs.

Alsanafi M, Salim NA, Sallam M.Hum Vaccin Immunother. 2023 Dec 31;19(1):2194772. doi: 10.1080/21645515.2023.2194772. Epub 2023 Apr 2.PMID: 37005342 Free PMC article.

KMEL References

https://pubmed.ncbi.nlm.nih.gov/

References

  1.  
    1. Barcelos AC, Michelin MA, Adad SJ, Murta EF. Atypical squamous cells of undetermined significance: Bethesda classification and association with human papillomavirus. Infect Dis Obstet Gynecol. 2011;2011 doi: 10.1155/2011/904674. 904674. - DOI - PMC - PubMed
  2.  
    1. Nayar R, Wilbur DC, editors. The Bethesda System for Reporting Cervical Cytology: Definitions, criteria and explanatory notes. 3rd ed. New York, USA: Springer; 2015.
  3.  
    1. Nascimento AF, Cibas ES. The ASC/SIL ratio for cytopathologists as a quality control measure: A follow-up study. Am J Clin Pathol. 2007;128:653–6. doi: 10.1309/aptvnlp1p0x00cuq. - DOI - PubMed
  4.  
    1. Bosch FX, Lorincz A, Muñoz N, Meijer CJ, Shah KV. The causal relation between human papillomavirus and cervical cancer. J Clin Pathol. 2002;55:244–65. doi: 10.1136/jcp.55.4.244. - DOI - PMC - PubMed
  5.  
    1. Johnston EI, Logani S. Cytologic diagnosis of atypical squamous cells of undetermined significance in perimenopausal and postmenopausal women: Lessons learned from human papillomavirus DNA testing. Cancer. 2007;111:160–5. doi: 10.1002/cncr.22687. - DOI - PubMed
  6.  
    1. Burd EM. Human papillomavirus and cervical cancer. Clin Microbiol Rev. 2003;16:1–17. doi: 10.1128/cmr.16.1.1-17.2003. - DOI - PMC - PubMed
  7.  
    1. Ali MAM, Bedair RN, Abd El Atti RM. Cervical high-risk human papillomavirus infection among women residing in the Gulf Cooperation Council countries: Prevalence, type-specific distribution and correlation with cervical cytology. Cancer Cytopathol. 2019;127:567–77. doi: 10.1002/cncy.22165. - DOI - PubMed
  8.  
    1. Mallik MK, Alramadhan B, Dashti H, Al-Shaheen A, Al Juwaiser A, Das DK, et al. Human papillomaviruses other than 16, 18 and 45 are the major high risk HPV genotypes amongst women with abnormal cervical smear cytology residing in Kuwait: Implications for future vaccination strategies. Diagn Cytopathol. 2018;46:1036–9. doi: 10.1002/dc.24035. - DOI - PubMed
  9.  
    1. Krishnan K, Thomas A. Correlation of cervical cytology with high-risk HPV molecular diagnosis, genotypes, and histopathology--A four year study from the UAE. Diagn Cytopathol. 2016;44:91–7. doi: 10.1002/dc.23391. - DOI - PubMed
  10.  
    1. Al-Awadhi R, Chehadeh W, Al-Jassar W, Al-Harmi J, Al-Saleh E, Kapila K. Viral load of human papillomavirus in women with normal and abnormal cervical cytology in Kuwait. J Infect Dev Ctries. 2013;15:130–6. doi: 10.3855/jidc.2748. - DOI - PubMed
  11.  
    1. Al-Awadhi R, Chehadeh W, Jaragh M, Al-Shaheen A, Sharma P, Kapila K. Distribution of human papillomavirus among women with abnormal cervical cytology in Kuwait. Diagn Cytopathol. 2013;41:107–14. doi: 10.1002/dc.21778. - DOI - PubMed
  12.  
    1. Cox JT. Management of women with cervical cytology interpreted as ASC-US or as ASC-H. Clin Obstet Gynecol. 2005;48:160–77. doi: 10.1097/01.grf.0000151571.91814.f3. - DOI - PubMed
  13.  
    1. Gupta S, Sodhani P. Reducing “atypical squamous cells” over-diagnosis on cervicovaginal smears by diligent cytology screening. Diagn Cytopathol. 2012;40:764–9. doi: 10.1002/dc.21621. - DOI - PubMed
  14.  
    1. Tewari R, Chaudhary A. Atypical squamous cells of undetermined significance: A follow up study. Med J Armed Forces India. 2010;66:225–7. doi: 10.1016/S0377-1237(10)80042-5. - DOI - PMC - PubMed
  15.  
    1. Yamamoto LS, Alves VA, Maeda MY, Longatto-Filho A, Utagawa ML, Eluf Neto J. A morphological protocol and guidelist on uterine cervix cytology associated to papillomavirus infection. Rev Inst Med Trop Sao Paulo. 2004;46:189–93. doi: 10.1590/s0036-46652004000400003. - DOI - PubMed
  16.  
    1. Saslow D, Solomon D, Lawson HW, Killackey M, Kulasingam SL, Cain J, et al. American Cancer Society, American Society for Colposcopy and Cervical Pathology, and American Society for Clinical Pathology screening guidelines for the prevention and early detection of cervical cancer. CA Cancer J Clin. 2012;62:147–172. doi: 10.3322/caac.21139. - DOI - PMC - PubMed
  17.  
    1. Youens KE, Hosler GA, Washington PJ, Jenevein EP, Murphy KM. Clinical experience with the Cervista HPV HR assay: Correlation of cytology and HPV status from 56,501 specimens. J Mol Diagn. 2011;13:160–6. doi: 10.1016/j.jmoldx.2010.11.016. - DOI - PMC - PubMed
  18.  
    1. Wright TC, Jr, Massad LS, Dunton CJ, Spitzer M, Wilkinson EJ, Solomon D, et al. 2006 consensus guidelines for the management of women with abnormal cervical screening tests. J Low Genit Tract Dis. 2007;11:201–22. doi: 10.1097/LGT.0b013e3181585870. - DOI - PubMed

Page Navigation