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.
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 p16 expression. HPV6-associated cervical tumors occurred at a low median age. HPV42/70 was associated with typical squamous cell carcinoma showing diffuse p16 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 p16 expression.
*IDIBELL, Institut Català d'Oncologia, L'Hospitalet de Llobregat (Barcelona), Spain †DDL Diagnostic Laboratory, Rijswijk, The Netherlands ‡Hospital del Mar, Barcelona, Spain §CIBER en Epidemiología y Salud Pública (CIBERESP), Barcelona, Spain ∥Consorci Sanitari Integral, Hospital General de l'Hospitalet, L'Hospitalet de Llobregat, (Barcelona), Spain ¶Instituto Nacional de Cancerología, Bogotá, Colombia #Instituto de Patología e Investigación, Universidad Nacional de Asunción, Paraguay.
Núria
N
Guimerà
Belén
B
Lloveras
Jan
J
Lindeman
Laia
L
Alemany
Miekel
M
van de Sandt
Maria
M
Alejo
Gustavo
G
Hernandez-Suarez
Ignacio G
IG
Bravo
Anco
A
Molijn
David
D
Jenkins
Antonio
A
Cubilla
Nubia
N
Muñoz
Silvia
S
de Sanjose
Francesc Xavier
FX
Bosch
Wim
W
Quint
D000328:Adult; D000368:Aged; D001005:Anus Neoplasms / Q000737:chemistry / Q000473:pathology / Q000821:virology*; D014408:Biomarkers, Tumor / Q000032:analysis; D001706:Biopsy; D002277:Carcinoma / Q000737:chemistry / Q000473:pathology / Q000821:virology*; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000032:analysis; D015344:DNA Probes, HPV; D004279:DNA, Viral / Q000032:analysis*; D005260:Female; D005833:Genital Neoplasms, Female / Q000737:chemistry / Q000473:pathology / Q000821:virology*; D005834:Genital Neoplasms, Male / Q000737:chemistry / Q000473:pathology / Q000821:virology*; D061809:Human Papillomavirus DNA Tests / Q000379:methods*; D052140:Human papillomavirus 11 / Q000235:genetics*; D052163:Human papillomavirus 6 / Q000235:genetics*; D006801:Humans; D007150:Immunohistochemistry; D061346:Laser Capture Microdissection; D008297:Male; D008875:Middle Aged; D030361:Papillomavirus Infections / Q000150:complications / Q000473:pathology / Q000821:virology*; D016133:Polymerase Chain Reaction; D011237:Predictive Value of Tests; D011379:Prognosis; D012307:Risk Factors
D014408:Biomarkers, Tumor; D019941:Cyclin-Dependent Kinase Inhibitor p16; D015344:DNA Probes, HPV; D004279:DNA, Viral