Skip Navigation LinksHome > September 2013 - Volume 37 - Issue 9 > The Occasional Role of Low-risk Human Papillomaviruses 6, 11...
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American Journal of Surgical Pathology:
doi: 10.1097/PAS.0b013e31828b6be4
Original Articles

The Occasional Role of Low-risk Human Papillomaviruses 6, 11, 42, 44, and 70 in Anogenital Carcinoma Defined by Laser Capture Microdissection/PCR Methodology: Results From a Global Study

Guimerà, Núria BSc*,†; Lloveras, Belén MD, PhD*,‡; Lindeman, Jan MD, PhD; Alemany, Laia MD*,§; van de Sandt, Miekel MD§; Alejo, Maria MD*,∥; Hernandez-Suarez, Gustavo MD; Bravo, Ignacio G. PhD*,§; Molijn, Anco MSc; Jenkins, David MD, PhD; Cubilla, Antonio MD, PhD#; Muñoz, Nubia MD, PhD*,¶; de Sanjose, Silvia MD, PhD*,§; Bosch, Francesc Xavier MD, PhD*; Quint, Wim PhD; on behalf of the RIS HPV TTHPV VVAPO study groups

Supplemental Author Material
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Abstract

Low-risk human papillomaviruses (LR-HPVs) have been associated occasionally with clinically and pathologically unusual anogenital malignancies. The relation between clinicopathologic features and any pathogenetic role of LR-HPV remains unclear. From a global study of 13,328 anogenital carcinomas, we identified 57 cases in which whole-tissue polymerase chain reaction using SPF10-LiPA25 showed single LR-HPV infection. In 43/46 (93.5%) available carcinomas, multiple polymerase chain reaction assays confirmed single detection of HPV6, 11, 42, 44, or 70 DNA. In 75% (n=32) of these, LR-HPV DNA was confirmed in tumor cells by laser capture microdissection. In 2 cases, including 1 adenocarcinoma, viral DNA was only found outside the tumor. All anogenital tumors with confirmed HPV6/11 showed a distinctive range of papillary, warty or warty-basaloid, squamous, or transitional histology with patchy or negative p16INK4a expression. HPV6-associated cervical tumors occurred at a low median age. HPV42/70 was associated with typical squamous cell carcinoma showing diffuse p16INK4a staining like high-risk HPV–related malignancies. HPV44 was found in malignant cells in 1 case. Viral taxonomy and theoretical analysis show that HPV6/11 belong to a different genus from HPV42/70 with E6/E7 gene products that would not bind pRb or p53, whereas HPV42/70 could bind pRb. Our data support the causal involvement of LR-HPVs in the carcinogenesis of <2% of anogenital malignancies of 2 distinct clinicopathologic patterns related to the genetic structure of the HPV types 6/11 and 70/42. HPV42/70 was associated with typical squamous carcinomas. Importantly all carcinomas associated with HPV6/11 globally showed verruco-papillary, well-differentiated, squamous, or transitional histology without p16INK4a expression.

© 2013 by Lippincott Williams & Wilkins.

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