P16^INK4aImmunostaining but Lack of Human Papilloma Virus Type 16 in Cutaneous Squamous Cell Carcinoma and Basal Cell Carcinoma: a Report from West Iran

Abstract

The tumor suppressor p16 is a biomarker for transforming human papilloma virus (HPV) infections that can lead to contradictory results in skin carcinomas. The aim of this study was to evaluate p16 expression and HPV-16 infection in the cutaneous basal cell carcinoma (BCC) and squamous cell carcinoma (SCC). This case-control study was performed on paraffin blocks of BCCs and SCCs and normal skin (53, 36, and 44 cases, respectively), between 2006 to 2015. Initial sections for groups were stained with hematoxylin and eosin (H & E). Immunohistochemistry was performed for p16 expression and human papilloma virus type 16 (HPV-16) infection. Normal group was skin of mammoplasty specimens and normal skin tissue in the periphery of tumors. The mean age at diagnosis was 42.1, 61.7 and 71.4 years for normal, BCC and SCC groups, respectively. P16 positivity was more in SCC and BCC groups compared to normal group (P<0.05) and HPV was negative in all patients in three groups. Also, the mean age at diagnosis and P16-positivity were higher for the SCC group than the BCC group (P<0.005). In conclusion, in non-melanoma skin cancers (SCC and BCC), p16-positivity can be a prognostic factor but there is no correlation between HPV-16 and p16 in these tumors.

Sun-Exposed versus Sun-Protected Cutaneous Basal Cell Carcinoma: Clinico-Pathological Profile and p16 Immunostaining

“…Our results are more consistent with those of Svensson et al and Eshkoor et al, who did not find evidence of such associations [ 8 , 19 , 38 ]. On the contrary, Conscience et al [ 18 ] showed a p16 over-expression in BCC located in sun-exposed areas, reflecting a significant association.…”

“…The p16 gene is supposed to be involved in the pathogenesis of cutaneous BCCs in view of increased p16 mRNA and also the expressed protein within tumor cells [ 6 , 7 ]. p16, a tumor suppressor, is a biomarker for transforming HPV infections and is validated as an accurate surrogate marker for HPV status determination in various types of tumors [ 8 , 9 ]. The p16/Rb/E2F regulatory pathway participates in cell cycle arrest and is inactivated in most human cancers, whereas p16INK4a is linked with CDK4 and CDK6 in competition with cyclin D1, which then prevents phosphorylation of the tumor-suppressor protein retinoblastoma (Rb), which contributes to form the pRbeE2F growth inhibitory complex and plays an important role in tumor pathogenesis [ 10 ].…”

Human papilloma virus infection in basal cell carcinoma of the skin: a systematic review and meta-analysis study

“…Out of 45 studies reported during 1991 to 2017; two studies were reported in Australia [12,13], one Romania [14], ten USA [15,16,17,18,19,20,21,22,23,24], one Argentina [1], four Netherlands [25,26,27,28], two Spain [8,11], one Brazil [29], one China [30], one UK [31], one Croatia [2], four Iran [9,32,33,34], one North Africa/France [35], one Germany/USA [36], two Greece [37,38], one Sweden/Austria [39], two Germany [40,41], five Italy [5,42,43,44,45], one Russia [46], one Germany/Poland [47], one Norway/Sweden [48] and two Sweden [49,50] (Table I). Fifteen studies were case-control and 30 studies were cross-sectional studies.…”

“…Fifteen studies were case-control and 30 studies were cross-sectional studies. Twenty-four studies did polymerase chain reaction (PCR) [1,2,12,14,19,20,21,25,28,29,31,32,35,36,37,39,40,41,42,43,44,46,47,49,50], 2 in situ hybridization (ISH) [15,18], 3 serology [16,48,24], 7 nested PCR [5,8,11,26,27,34,43], one loop-mediated isothermal amplification assay (LAMP)/PCR [30], 4 multiplex serology [17,22,38,45], 2 immunohistochemistry (IHC) [9,33] Meta-analysis Figure 2 shows the incidence of number of HPVs in the BCC patients and controls. Some studies reported this incidence in the BCC patients and controls (case-control studies) and other studies only reported in BCC patients (cross-sectional and cohort studies).…”