New Treatment for Skin Cancer - Skin Cancer Vaccine (Part One)

Cutaneous tumor, also known as skin cancer, is a cancer caused by the skin. Cutaneous tumor is the most common form of cancer, accounting for at least 40% of the cases around the world. There are four main types of cutaneous skin cancers: melanoma, basal cell carcinoma (BCC), squamous cell carcinoma (SCC) and merkel cell carcinoma (MCC).

1. Squamous Cell Carcinoma

Squamous cell carcinoma is more likely to be aggressive. It usually presents as a hard lump with a scaly top but may also form ulcers. It can be transformed from keratosis, leukoplakia and other precancerous conditions. It grows faster and forms ulcers in the early stages. Some are nodular, milky or cauliflower-like, with less invasion to the deep, and the base can move; some are butterfly-like, infiltrating deep into the body, and are more destructive, often involving the bones. Squamous cell carcinoma is associated with a sticky pus with malodor and pain. Squamous cell carcinoma has a higher degree of malignancy, and is more likely to metastasize, more commonly regional lymph node metastasis.

The incidence of SCC varies in age, gender, race, geography, and genetics. SCC occurs in older people over the age of 50, but the most common is 70 years old and the prevalence of men is twice that of women. People with type I and type II skin are at high risk, and those who are often exposed to intense sunlight and who do not have adequate protection from the skin are at high risk.

SCC occurs mainly in the skin of the exposed area, especially the face, neck and back of the hand. SCC occurring in the lips and auricles is more aggressive, and other SCCs including the pharynx, external genitalia, and around the nail may be associated with HPV infection. SCC around the nail is easily misdiagnosed as hyperthyroidism or paronychia, and the recurrence rate of SCC in these areas is higher, up to 30%. Most invasive SCC occurs in the head and neck, followed by the trunk. The lesions are solid, skin-colored or pink, smooth or hyperkeratotic papules, nodules or plaques, and ulceration may occur. The skin lesions are asymptomatic or occasionally itching, and the ulcer may be painful or bleeding. SCC can be complicated by other chronic inflammatory skin diseases (such as discoid lupus erythematosus, lichen planus, and dystrophic bullous epidermis), chronic skin ulcers, sinus, and burn scars, making skin damage more performance complex.

Human papilloma virus (HPV) features a great variety of species and classifications．Sorted by susceptible cell types, its clinical manifestations can be skin-related, wart-related or mucosa-related. Classified by its biological behavior, it can be high-risk or low risk. High-risk HPV could cause malignancies, for example, HPV16 and HPV18 are the high-risk species causing most cervical carcinoma. Other HPV-related carcinomas, such as oropharyngeal carcinoma and high-risk HPV non-melanoma skin cancer have been the focus of research for many years． Research on HPV pathogenesis has increased our understanding of the pathogenesis, diagnosis and treatment of cancers. Advent of prophylactic HPV vaccine made cervical cancer the first preventable cancer, and also prevented the occurrence of sexually transmitted condyloma acuminate.

The HPV family is huge and its classification methods are different. According to the biological behavior of HPV, it is divided into low-risk type and high-risk type. Low-risk HPV mainly causes mucosal hyperplasia, and high-risk type is associated with the occurrence of cervical cancer and oropharyngeal cancer. According to the homology of gene sequences, HPV is divided into 16 genera such as α, β and γ. Among them, α-HPV is more studied, and its subtype can cause cervical cancer, anal genital warts and skin spasm; β- There are 25 subtypes of HPV, which are closely related to the occurrence of non-melanoma skin cancer. With the increasing incidence of β-HPV, the research of β-HPV has become a research hotspot. The detection rate of β-HPV, especially HPV38 subtype, in skin squamous cell carcinoma and solar keratoderma lesions is much higher than that of the control group. It is believed that HPV38 is likely to cause skin squamous cell carcinoma and solar keratosis. "High-risk subtype".

In addition to classification according to genus, HPV is also divided into mucosa type, sputum-related type and skin type according to different clinical manifestations and viral infection sites. Mucosal HPV mainly refers to HPV associated with anal genital and oropharyngeal mucosa. These subtypes HPV has a high degree of tissue specificity, and different subtypes are susceptible to different parts of the infection and cause corresponding diseases. Warts related HPV refers to HPV associated with skin such as common warts, flat warts, and warts, including some low-risk α-HPV; skin-type HPV is β-HPV, first known as epidermodysplasia verruciformis-associated HPVs, EV-HPV as described above, it is closely related to the occurrence of non-melanoma skin cancer.

HPV infection has a high degree of epitheliality and selectively infects skin and mucosal epithelial cells. Skin or mucosal damage is the initiation condition of HPV infection, and the gene is encoded and replicated after virus invasion. There are 8 kinds of HPV-encoded gene proteins, 6 early genes (E), which are responsible for virus replication, transcription and regulation. The late genes (L) are responsible for the coding of viral capsid proteins. Viral infection of basal cells, integration with host cells is an important factor leading to persistent viral infection.

HPV infection of the skin and mucous membranes can cause a variety of benign and malignant changes, and the skin lesions of different HPV type infections are also different. Skin sputum-associated HPV, such as HPV1, 2, 3, 4, 27, 57, 41 infections can cause benign skin spasms. Common warts, flat warts, and warts are the most common skin blemishes. The incidence rate is as high as 33% in children and adolescents. The rash occurs on the face, hands and soles. It is a round papule with a keratinized surface. Hyperplasia. In people with normal immunity, the course of skin spasm is self-limiting, and the rash can resolve without leaving traces. Epidermodysplasia verruciformis (EV) is a rare hereditary skin disease that is particularly susceptible to β-HPV, especially HPV 5 and 8. The rash is mostly flat and sinuous, symmetrically distributed, and can be spread throughout the body. Due to the large number of rashes, the current treatment is still difficult. About half of the patients can eventually develop into squamous cell carcinoma of the skin, especially the exposed parts of the skin, suggesting that the progression of EV is progressing. May be related to long-term exposure to ultraviolet light.

The HPV vaccine is effective in preventing HPV infection. There are currently three HPV vaccines that prevent HPV infection, one is the bivalent cervarix vaccine, which is mainly for type 16 and type 18 HPV infections; the other is the tetravalent gardasil cervical cancer vaccine. It can prevent HPV infections of type 6, 11, 16 and 18; the nine-valent vaccine is based on the first two and adds five subtypes, namely HPV31, 33, 45, 52 and 58. Among them, the four-valent, nine-valent gardasil vaccine not only prevents cervical cancer, but also prevents the occurrence of genital warts by preventing HPV6 and 11 infection. The clinical use of HPV prophylactic vaccines in foreign countries has been more than ten years. In addition to HPV preventive vaccines, the prevention of genital warts is mainly achieved by regulating the use of condoms and reducing sexual partners. Non-melanoma skin cancer can be reduced by reducing ultraviolet radiation.

To be continued in Part Two…