Nutrition and nonmelanoma skin cancers

The incidence of nonmelanoma skin cancer is increasing every year. Basal cell carcinoma and squamous cell carcinoma are the two major types of nonmelanoma skin cancer. Among other factors, understanding the potential role of nutrients in the development, progression, and treatment of nonmelanoma skin cancer is critical. This contribution provides a review of the nutrients that have been more extensively investigated in the literature with regard to nonmelanoma skin cancer, including dietary fats, retinol, carotenoids, vitamin C, vitamin D, vitamin E, selenium, copper, iron, zinc, green tea, and black tea.     

Nutrition and nonmelanoma skin cancers

Nonmelanoma skin cancer (NMSC), the most widely diagnosed cancer in the United States, is rising in incidence despite public health and educational campaigns that highlight the importance of sun avoidance. It is,therefore, important to establish other modifiable risk factors that may be contributing to this increase. There is a growing body of evidence in the literature suggesting certain nutrients may have protective or harmful effects on NMSC. We review the current literature on nutrition and its effect on NMSC with a focus on dietary fat, vitamin A, nicotinamide, folate, vitamin C, vitamin D, vitamin E, polyphenols, and selenium.     

Human papillomavirus status in extragenital nonmelanoma skin cancers

About 5% of all cancers worldwide can be attributed to human papillomaviruses (HPVs); namely, six sites are strongly associated with HPV infections: cervix, penis, vulva, vagina, anus, and oropharynx. Nonmelanoma skin cancers (NMSC), basal cell carcinoma (BCC), and squamous cell carcinoma (SCC) are the most common malignancies in Caucasians. In fact, there is an intense connection between sunlight exposure, fair skin, HPV, and development of NMSC. We have conducted a pilot study that included tissue samples from 26 carcinoma patients, of which there were 13 BCC and 13 SCC. HPV detection and typing was done with DNA amplification and sequencing, respectively. In total, 23.1% of SCC samples (3/13) and 7.7% of BCC samples (1/13) were positive for HPV DNA. The importance of understanding all aspects of NMSC carcinogenesis may be to reveal novel therapeutic options or preventive measures for HPV containing NMSC patients.     

Immunohistochemical differentiation of extra-ocular sebaceous carcinoma from other skin cancers

We performed an immunohistochemical study using routinely processed formalin-fixed and paraffin-embedded tissue specimens from 26 cases of extra-ocular sebaceous carcinoma (EOSC) and eight easily available antibodies. They were polyclonal anti-carcinoembryonic antigen (CEA) antibody, monoclonal anti-CEA antibody, anti-breast carcinoma associated antigen-225 antibody (CU18), anti-CA15.3 antibody (CA15.3), anti-CD15 antibody (CD15), anti-breast carcinoma associated antigen antibody (B6.2), anti-gross cystic disease fluid antigen-15 antibody (GCDFP15) and anti-Thomsen-Friedenreich antigen antibody (TFA). Squamous cell carcinoma, porocarcinoma, syringomatous carcinoma, malignant clear cell hidradenoma, apocrine adenocarcinoma, and extramammary Paget's disease with underlying adenocarcinoma were used as controls. EOSC was positive for CU18 and CA15.3 in most cases, and for CD15 in a few cases. Squamous cell carcinoma of the skin was positive for CA15.3 in only one case. Porocarcinoma, syringomatous carcinoma and malignant clear cell hidradenoma were positive for CEA, CU18, CA15.3, and B6.2 in most cases. Apocrine adenocarcinoma and extramammary Paget's disease with underlying adenocarcinoma were positive for CEA, CU18, CD15, GCDFP15, CA15.3, and B6.2 in most cases. TFA was positive not only in EOSC but also in other skin cancers. Immunohistochemical examinations using these seven of eight antibodies except for TFA and routinely processed formalin-fixed and paraffin-embedded tissue specimens are beneficial in differentiating EOSC from other skin cancers.     

The sap from Euphorbia peplus is effective against human nonmelanoma skin cancers

Background The sap from Euphorbia peplus, commonly known as petty spurge in the U.K. or radium weed in Australia, has been used as a traditional treatment for a number of cancers. Objective To determine the effectiveness of E. peplus sap in a phase I/II clinical study for the topical treatment of basal cell carcinomas (BCC), squamous cell carcinomas (SCC) and intraepidermal carcinomas (IEC). Methods Thirty‐six patients, who had refused, failed or were unsuitable for conventional treatment, were enrolled in a phase I/II clinical study. A total of 48 skin cancer lesions were treated topically with 100–300 μL of E. peplus sap once daily for 3 days. Results The complete clinical response rates at 1 month were 82% (n = 28) for BCC, 94% (n = 16) for IEC and 75% (n = 4) for SCC. After a mean follow‐up of 15 months these rates were 57%, 75% and 50%, respectively. For superficial lesions < 16 mm, the response rates after follow‐up were 100% for IEC (n = 10) and 78% for BCC (n = 9). Conclusions The clinical responses for these relatively unfavourable lesions (43% had failed previous treatments, 35% were situated in the head and neck region and 30% were > 2 cm in diameter), are comparable with existing nonsurgical treatments. An active ingredient of E. peplus sap has been identified as ingenol mebutate (PEP005). This clinical study affirms community experience with E. peplus sap, and supports further clinical development of PEP005 for the treatment of BCC, SCC and IEC.     

Viral DNA detection and RAS mutations in actinic keratosis and nonmelanoma skin cancers

Background Actinic keratosis (AK) is a well‐established precancerous skin lesion that has the potential to progress to squamous cell carcinoma (SCC). Basal cell carcinoma (BCC) is a locally aggressive slowly growing tumour that rarely metastasizes. A number of viruses have been proposed to play a role in the development of nonmelanoma skin cancers (NMSC), but the most plausible evidence to date suggests that cutaneous human papillomavirus (HPV) is the key instigating factor. Objectives To evaluate the prevalence of HPV, cytomegalovirus (CMV), herpes simplex virus (HSV) and Epstein–Barr virus (EBV) and investigate their relationship with the presence of RAS gene mutations in cutaneous lesions obtained from nonimmunosuppressed patients. Methods HPV, CMV, HSV and EBV detection was performed using polymerase chain reaction (PCR) in skin biopsies (26 AK, 12 SCC and 15 BCC samples) that were collected from immunocompetent patients. The RAS mutation incidence was also investigated in all cutaneous lesions by use of PCR/restriction fragment length polymorphism and direct DNA sequencing. Results Seventeen out of 53 (32%) skin lesions were found to be positive for HPV DNA. The highest incidences of HPV infection were five of 15 (33%) in BCC and four of 12 (33%) in SCC specimens. The HPV incidence was eight of 26 (31%) in AK and eight of 53 (15%) in normal skin tissue. Twelve out of 53 (23%) skin lesions were CMV‐positive. The highest incidence of CMV infection was six of 15 (40%), observed in BCC specimens. The CMV incidence was two of 26 (8%) in AK and four of 12 (33%) in SCC. No normal skin biopsy was found to be positive for CMV. All cutaneous samples were negative for HSV and EBV DNA, as assessed by our PCR‐based assays. Only three samples, one AK (4%), one BCC (6%) and one SCC (8%), were found to carry a G>T transversion at the second position of HRAS codon 12. Both HRAS mutant SCC and BCC biopsies were HPV‐ and CMV‐positive, as well. Conclusions HPV DNA is detected in NMSC, AK and normal skin biopsies. Our results also indicate that CMV is involved in NMSC at higher levels than in premalignant lesions, whereas the virus was not detected in normal skin biopsies. HSV and EBV do not appear to be involved in the pathogenesis of cutaneous lesions. Moreover, we suggest that the HRAS codon 12 mutation is not a very common event in AK or NMSC. Finally, both viral infection and HRAS activation appear to represent independent factors in the aetiology of NMSC, samples of which were obtained from immunocompetent patients.     

Trends of nonmelanoma skin cancer from 1960 through 2000 in a Canadian population

Nonmelanoma skin cancer (NMSC) is the most common malignancy diagnosed in Caucasian populations, but little is known about its occurrence in Canada. We sought to determine the historical change of the occurrence and risk of NMSC. All first diagnoses of NMSC reported in Manitoba between 1960 and 2000 were identified. Rates were reported as well as lifetime risk of developing the disease. Basal cell carcinoma was the predominant form of NMSC, accounting for 79% of all NMSCs. The annual percentage change of basal cell and squamous cell carcinoma increased 2.4%, mainly in people older than 40 years of age from the early 1970s to 2000. The lifetime risk of being diagnosed with NMSC increased by two to three times in the 1990s compared to the 1960s. We concluded that because of the potentially high impact of NMSC on resource utilization and treatment-related costs as well as its easily preventable character, priority should be given to prophylactic measures.