Background: Atypical squamous cells of undetermined significance (ASCUS) remain the center of diagnostic controversy and patients’ stress despite recent advances in cervical cancer screening and the introduction of human papilloma virus (HPV) testing. The role of infectious agents in the induction of such changes is not well understood. Aim: We aim at reviewing the effect of the different infectious organisms in Papanicolaou (PAP) smears on the ASCUS diagnosis. Material: 133 ASCUS cases associated with variable infectious organisms (ASCUS-infection group) with secondary HPV testing and appropriate follow-up studies were reviewed. A control group of 310 ASCUS cases without any organisms (ASCUS-only group) was selected for comparison. Results: The ASCUS-infection group had a significantly higher proportion of HPV-positive tests than the ASCUS-only group (p = 0.0027). There was no significant difference on follow-up PAPs and biopsies between the two groups (p = 0.4272). They showed an overall mean of 75% negative, 20% low-grade lesions, and 5% high-grade lesions/carcinoma in situ on follow-up. Conclusion: Our study demonstrates no significant effect of infections on the cytological changes diagnostic of ASCUS. The cytologist should make this diagnosis neglecting any background infections even when predominant.

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