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abnormality in DCS. Although the function of the CLE is still unclear, a role as a necessary scaffold for the lamellar bilayer organization is likely (Uchida and Holleran, 2008). Thus, CLE deficiency, coupled with disorganization of extracellular lamellar bilayers, likely merge to provoke the barrier abnormality in NLSDI (see Supplementary Figure S2 online). Finally, to overcome this metabolic disadvantage in forming the epidermal permeability barrier, epidermal proliferation likely increases, which in turn results in hyperkeratosis, phenotypic features common to virtually all of the ichthyoses (Demerjian et al., 2006; Akiyama et al., 2008), that is, 'A compromised permeability barrier 'drives' the hyperproliferative epidermis in NLSDI and other ichthyoses' (Elias et al., 2008).

HPV16 is the most carcinogenic human papillomavirus and causes >50% of cervical cancers, the majority of anal cancers and 30% of oropharyngeal squamous cell carcinomas. HPV carcinogenesis relies on the continuous expression of the two main viral oncoproteins E6 and E7 that target >150 cellular proteins. Among them, epigenetic modifiers, including DNA Methyl Transferases (DNMT), are dysregulated, promoting an aberrant methylation pattern in HPV-positive cancer cells. It has been previously reported that the treatment of HPV-positive cervical cancer cells with DNMT inhibitor 5-aza-2'-deoxycytidine (5azadC) caused the downregulation of E6 expression due to mRNA destabilization that was mediated by miR-375. Recently, the T-box transcription factor 2 (TBX2) has been demonstrated to repress HPV LCR activity. In the current study, the role of TBX2 in E6 repression was investigated in HPV16 cervical cancer cell lines following 5azadC treatment. A decrease of E6 expression was accompanied by p53 and p21 restoration. While TBX2 mRNA was upregulated in 5azadC-treated SiHa and Ca Ski cells, TBX2 protein was not detectable. Furthermore, the overexpression of TBX2 protein in cervical cancer cells did not allow the repression of E6 expression. The TBX2 transcription factor is therefore unlikely to be associated with the repression of E6 following 5azadC treatment of SiHa and Ca Ski cells.

References1 Rubegni P, Burroni M, Sbano P, Andreassi L. Digital dermoscopy analysis and internet-based program for discrimination of pigmented skin lesion dermoscopic images. Br J Dermatol 2005; 152:395-6. 2 Oka H, Hashimoto M, Iyatomi H et al. Internet-based program for automatic discrimination of dermoscopic images between melanomas and Clark naevi. Br J Dermatol 2004; 150:1041 (Letter). SIR, We read with interest the recent article by La Placa et al. 1 investigating the detection of high-risk (HR) mucosal human papillomavirus (HPV) in primary melanoma (PM) and in acquired dysplastic melanocytic naevi. Using two different polymerase chain reaction (PCR)-enzyme-linked immunosorbent assay methods, the authors found HR HPV genotypes in 24% of acquired dysplastic melanocytic naevi and in 27% of 14 PMs compared with 0% in the control skin samples. However, we wish to make the following comments. Five of 14 melanoma patients positive for HPV DNA were aged over 67 years, and there is evidence showing an association between HPV infection and ageing in immunocompetent patients or in patients with a history of cutaneous skin cancer. 2 Only three studies 3-5 regarding the association between melanoma and HPV are available. First, using a nonspecific polyclonal antibody raised against bovine papillomavirus 1, Dreau et al. 3 found HPV in 58% of 12 melanomas. Then, using PCR followed by sequencing, Miracco et al. 4 observed only one case among 54 malignant melanomas of mucosal HR HPV-16 DNA.Finally, seroreactivity to HPV-16 was studied in 84 patients with malignant melanoma and no association for HPV-16 serorecognition was found. 5 A significant problem for investigations of an association between HPV and skin cancer is that HPV is part of the microbiological flora of healthy human skin. Indeed, high detection rates (25-65%) of both HR mucosal and cutaneous HPV DNA have been found in healthy skin biopsies, plucked hairs and skin swab samples in large series of immunocompetent individuals. 6 An impressive diversity of known HPV types or putative novel types was identified by sequencing. In general, higher detection rates were found with primers detecting epidermodysplasia verruciformis-related HPV types compared with primers allowing the detection of mucosal DNA HPV. However, HR HPV DNA, especially oncogenic HPV-16, is frequently detected in distal digital and periungual skin in contrast to other skin areas, suggesting a genital-digital mode of transmission. 7 Thus, skin HPVs represent ubiquitous viruses, highly prevalent in the normal skin of healthy adults and causing asymptomatic infections likely to be acquired very early in infancy. 8 This may suggest a commensalic nature, and HPV positivity in skin tumours may merely reflect contamination of the tumours by viral HPV DNA or by particles harboured in cells shed from infected healthy skin. 9 It should be noted that in all previous studies regarding the presence of HPV in malignant melanoma, no sample of normal skin from the same patients was investigated.Altogether, the ex...

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