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• Anal Intraepithelial Neoplasia: the role of high risk HPV
  Atef R Markos
  Published on: 13 May 2016

• Published on: 13 May 2016

  Anal Intraepithelial Neoplasia: the role of high risk HPV

  • Atef R Markos, Consultant in Genito Urinary Medicine & Sexual Health

  Dear Editor,

  We read with interest the Fox PA et al. paper (2005, 81;142-6) and welcome the clinical attention to genital pre-cancerous conditions; including Anal Intraepithelial Neoplasia (AIN).

  Their finding of no correlation between high-risk (hr) HPV genotypes and histological or cytological grades of abnormalities, conflicts strongly with general consensus and other studies. Kreuter A et al. identified hr H...

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  Dear Editor,

  We read with interest the Fox PA et al. paper (2005, 81;142-6) and welcome the clinical attention to genital pre-cancerous conditions; including Anal Intraepithelial Neoplasia (AIN).

  Their finding of no correlation between high-risk (hr) HPV genotypes and histological or cytological grades of abnormalities, conflicts strongly with general consensus and other studies. Kreuter A et al. identified hr HPV in all AIN cases (with up to 7 different high-risk and 5 different low-risk types per lesion, with HPV – 16 always present in verrucous AIN).[1] Similar findings were corroborated by Daling JR et al., who support an important role for HPV in ano-genital cancer, at all sites.[2] They identified HPV in 88% of all histological specimens with HPV - 16 identified in 73%. It also contradicts Frisch M et al. paper, where 95% and 80% of anal canal and 83% and 28% of perianal skin cancers, of women and men respectively, were hr HPV positive.[3]

  Van der Snoek EM et al. reported that 64.7% of the HIV positive men have HPV DNA more often in anal specimens than on the coronal sulcus (23.5%). The later finding is plausible, on account of the vulnerability of the squamo columnar junction and transformation zone of the anal canal to harbour and retain HPV particles (with consequent neoplastic transformation).[4] Understandably, the contradiction of the Fox et al. study will raise a prima facie question about their HPV detectability and virological techniques.

  The PA Fox study documents the right observations regarding the aceto white areas without making the correct conclusions. We note that histological biopsies of suspicious aceto white areas in the study reports 81% concordance with AIN lesions, which suggests good prediction and appraise the test value.

  The factors leading the clinical appraisal of ano-genital pre-cancerous conditions are:

  1. They behave similarly: recurrent, multi-focal, potentially cancerous, increasing in incidence and overlooked by cosmetic factors (eg genital warts).

  2. The incidence of genital cancer (anal, vulval, penile) is increasing.[5]

  3. Patient's age of genital cancer and pre-cancerous conditions is declining, [6] (which brings them into the GUM clinics' age groups).

  4. The increase in incidence of HPV related lesions is paralleled with increase in oncogenesis and genital intraepithelial neoplasias.[6] There could be a false increase due to the discovery of a pre-existing lesion (brought about by worries following a sexual encounter).

  5. GUM physicians are in a special position, as they deal routinely with the ano genital area, which impose a duty of care to exclude intraepithelial neoplasia between other genital lesions. The similarities of symptoms and signs of AIN with anal warts were confirmed in the PA Fox paper.

  6. The natural history is not fully appraised, due to the relative small caseload.

  7. Long-term follow-up is prudent, since 23 of 29 HIV positive patients in one study had persistent or recurrent high grade AIN with 12 month mean time of recurrence.[7]

  References

  1. Kreuter A, Brockmeyer NH, Hochdorfer B, et al: Clinical spectrum and virologic characteristics of anal intraepithelial neoplasia in HIV infection. J Am Acad Dermatol, 2005; 52(4):603-8.

  2. Daling JR, Madeleine MM, Johnson LG, et al: Human papillomavirus, smoking, and sexual practices in the etiology of anal cancer. Cancer, 2004 15;101(2):270-80.

  3. Frisch M, Fenger C, van den Brule AJ, et al: Variants of squamous cell carcinoma of the anal canal and perianal skin and their relation to human papillomavirus. Cancer Res, 1999 1;59(3):753-7.

  4. van der Snoek EM, Niesters HG, Mulder PG, et al: Human papillomavirus infection in men who have sex with men participating in a Dutch gay-cohort study. Sex Transm Dis, 2003;30(8):639-44.

  5. Johnson LG, Madeleine MM, Newcomer LM, et al: Anal cancer incidence and survival: the surveillance, epidemiology, and end results experience, 1973-2000. Cancer, 2004 15;101(2):281-8.

  6. Frisch M: On the etiology of anal squamous carcinoma. Dan Med Bull, 2002;49(3):194-209.

  7. Chang GJ, Berry JM, Jay N, et al: Surgical treatment of high-grade anal squamous intraepithelial lesions: a prospective study. Dis Colon Rectum, 2002;45(4):453-8.

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  Conflict of Interest:
  None declared.

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