Prevalence of Human Papillomavirus Types in Invasive Vulvar Cancers and Vulvar Intraepithelial Neoplasia 3 in the United States Before Vaccine Introduction

Abstract

Objective To determine the baseline prevalence of human papillomavirus (HPV) types in invasive vulvar cancers (IVC) and vulvar intraepithelial neoplasia 3 (VIN3) using data from 7 United States cancer registries. Materials and Methods Registries identified eligible cases diagnosed in 1994–2005 and requested pathology laboratories to prepare one representative block for HPV testing on those selected. Hematoxylin and eosin stained (H&E) sections preceding and following those used for extraction were reviewed to confirm representation. HPV was detected using L1 consensus PCR with PGMY9/11 primers and type specific hybridization, with retesting of negative and inadequate samples with SPF10 primers. For IVC, the confirmatory H&E slides were re-evaluated to determine histologic type. Descriptive analyses were performed to examine distributions of HPV by histology and other factors. Results HPV was detected in 121/176 (68.8%) IVC and 66/68 (97.1%) VIN3 (p<.0001). IVC and VIN3 differed by median age (70 years vs. 55 years, p=.003). HPV16 was present in 48.6% of IVC and 80.9% of VIN3; other high-risk (HR) HPV was present in 19.2% of IVC and 13.2% of VIN3. HPV prevalence differed by squamous cell carcinoma (SCC) histologic subtype (p<.0001): keratinizing, 49.1% (n=55); non-keratinizing, 85.7% (n=14), basaloid, 92.3% (n=14), warty 78.2% (n=55), and mixed warty/basaloid, 100% (n=7). Conclusions Nearly all VIN3 and two-thirds of IVC were HR-HPV positive. HPV prevalence ranged from 49.1–100% across SCC histologic subtypes. Given the high prevalence of HPV in IVC and VIN3, prophylactic vaccines have the potential to decrease the incidence of vulvar neoplasia.

HPV Detection and Genotyping in Vulvar Squamous Cell Carcinoma in Northern Thailand

“…Almost one half of cases with keratinizing SCC were HPV-positive in our study similar to the finding in a previous report from the United States (Gargano et al, 2012). In previous studies, the prevalence of HPV in keratinizing SCC (range 6% to 49%) was lower than that of the other subtypes of vulvar SCC which ranged from 70% to 92% (De Vuyst et al, 2009;Smith et al, 2009;Gargano et al, 2012;de Sanjose et al, 2013). However, there is still an overlapping spectrum of subtypes between HPV-positive and HPVnegative SCC, and this causes difficulty in the prediction of HPV status based on the morphology of SCC alone (Del Pino et al, 2013).…”

“…HPV-negative SCC is also associated with differentiated-type VIN or lichen sclerosus (Pinto et al, 2010;Alonso et al, 2011). Almost one half of cases with keratinizing SCC were HPV-positive in our study similar to the finding in a previous report from the United States (Gargano et al, 2012). In previous studies, the prevalence of HPV in keratinizing SCC (range 6% to 49%) was lower than that of the other subtypes of vulvar SCC which ranged from 70% to 92% (De Vuyst et al, 2009;Smith et al, 2009;Gargano et al, 2012;de Sanjose et al, 2013).…”

“…This prevalence is higher than that reported in the previous smaller series from Thailand (44%) , but is comparable to the HPV prevalence range of 59% to 70% reported in the vulvar cancer studies from North America (Insinga et al, 2008;Sutton et al, 2008;De Vuyst et al, 2009;Smith et al, 2009;Gargano et al, 2012). There appears to be a geographic variation in the prevalence of HPV infection in vulvar SCC.…”

“…The HPV prevalence in this study and in the studies from North America was higher than that reported from East Asia (38%), Europe (33-35%), Oceania (29%), and South America (24%) (De Vuyst et al, 2009;Smith et al, 2009). The difference may be partly related to the types of specimen used in each study, the variation in the distribution of SCC subtypes, or the variation in HPV detection techniques (Smith et al, 2009;Gargano et al, 2012;de Sanjose et al, 2013). The latter possibility is supported by cervical cancer studies where an increase in HPV detection rate may link to recent advances in HPV detection systems (Li et al, 2011).…”

“…The latter possibility is supported by cervical cancer studies where an increase in HPV detection rate may link to recent advances in HPV detection systems (Li et al, 2011). However, it should be noted that the regional difference in HPV prevalence between North America and Europe could still be observed in the recent studies using the current sensitive HPV detection assays (50-70% vs 15-35%, respectively) (Riethdorf et al, 2004;Sutton et al, 2008;Kowalewska et al, 2010;Alonso et al, 2011;Gargano et al, 2012;de Sanjose et al, 2013).…”