Non-16/non-18 high-risk human papillomavirus types predominate in anal cytology categories of negative for intraepithelial lesion and atypical cells of undetermined significance

Introduction: Screening for anal carcinoma continues to grow despite controversy regarding its efficacy. High-risk human papillomavirus (HR-HPV) has been adopted as a cotest with anal Papanicolaou tests. We sought to identify the prevalence of HR-HPV types in the most common anal cytology specimens: negative for intraepithelial lesion or malignancy (NILM) and atypical squamous cell of undetermined significance (ASC-US).

Materials and methods: Anal cytology specimens were identified and tested for HR-HPV using Roche cobas 4800 HR-HPV analysis (Roche Molecular Systems, Inc., Indianapolis, Ind) and, if positive, typed further for: HPV-16, -18, and/or non-16/non-18 "other" HR-HPV type.

Results: There were 642 specimens from 538 patients. The most common interpretation was NILM (48.6%) and ASC-US (25.7%). Of NILM cases, 47% were HR-HPV+ (53% in men, 33% in women, P = 0.03, χ²). In ASC-US cases, 73% were HR-HPV+ (74% in male patients, 70% in female patients). The most common HPV subtype was non-16/non-18 HR-HPV "other" types in 89% of cases. HPV-16 and HPV-18 were positive in 35% and 18% of cases, respectively. In patients with non-16/non-18 HR-HPV+ anal cytology, 16 of 79 had biopsies histologically diagnosed as at least high-grade squamous intraepithelial lesion (HSIL+). However, the relative risk of having HSIL+ was 2.3-times higher for anal cytology positive for HPV-16, -18, with/without coinfection with non-16/non-18 HR-HPV than those positive for non-16/non-18 "other" HR-HPV types alone.

Conclusions: Non-16/non-18 "other" HR-HPV types are most prevalent in anal cytology interpretations of NILM and ASC-US. Patients with HR-HPV+ NILM or ASC-US, negative for HPV-16/-18, are at lower relative risk of having subsequent histologic HSIL+, but a percentage of these patients still harbor HSIL+ on biopsy.