Histological characteristics of HPV-associated and -independent squamous cell carcinomas of the vulva: A study of 1594 cases

• Published in: International journal of cancer
• Main Authors: Rakislova, Natalia, Clavero, Omar, Alemany i Vilches, Laia, Saco, Adela, Quirós, Beatriz, Lloveras Rubio, Belén, Alejo, Maria, Pawlita, Michael, Quint, Wim, Pino, Marta del, Sanjosé Llongueras, Silvia de, Ordi i Majà, Jaume
• Format: Journal Article
• Language: English
• Published: Wiley 31-08-2017
• Subjects: Malalties de la vulva; Papillomaviruses; Papil·lomavirus; Vulva diseases
• ISSN: 0020-7136

There are at least two different etio-pathogenic pathways for
the development of vulvar squamous cell carcinoma (VSCC): one
associated with infection by human papillomavirus (HPV) and
another independent of HPV. We aimed to describe the
histological characteristics of HPV-associated and
HPV-independent tumors and to determine the best strategy to
identify HPV in VSCC. A single paraffin block was available for
review from a series of 1594 VSCCs. In all cases HPV DNA
detection was analyzed using the SPF10PCR/DEIA/LiPA25 system and
p16 immunohistochemistry (IHC). A tumor was considered as
unquestionably HPV-associated if both HPV DNA and p16 IHC were
positive. A tumor was considered indisputably HPV-independent if
both HPV DNA and p16 IHC were negative. Two groups of tumors
were classified as non-conclusive: 1) HPV DNA+/p16-; and 2) HPV
DNA-/p16+. WHO typing and a thorough histological evaluation
were conducted in all cases. 441 tumors were HPV DNA+ with 367
cases (23.0%) being HPV DNA+/p16+. These HPV DNA+/p16+ tumors
were more frequently basaloid or warty (49.8%), but 36.5% were
of the keratinizing type. 1153 tumors were HPV DNA-, with 1060
cases (66.5%) being HPV DNA-/p16-. These HPV DNA-/p16- tumors
were mostly keratinizing (81.2%) but were occasionally basaloid
or warty (5.2%). The features of HPV DNA-/p16+ cases (n=93) were
similar to those of the HPV-associated VSCC, and HPV DNA+/p16-
(n=74) cases had a more diverse profile, although they were more
similar to HPV-independent tumors. Several histological
characteristics were more frequently associated with HPV-related
VSCC (koilocytotic-like change, necrosis, moderate to marked
pleomorphism, invasive front in nests; p<0.001), however,
none of these characteristics allowed differentiation between
HPV-associated and -independent VSCC. In conclusion,
histological criteria do not allow differentiation between
HPV-associated and -independent VSCC. p16 alone is a clinically
easy strategy to determine HPV status in VSCC. This article is
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