Worldwide cutaneous malignant melanoma incidences analyzed by sex, age, and skin type over time (1955–2007): Is HPV infection of androgenic hair follicular melanocytes a risk factor for developing melanoma exclusively in people of European-ancestry?

Abstract

The cutaneous malignant melanoma (CMM) incidence has been increasing in an exponential manner in certain populations around the world for over 7 decades. To help illuminate the etiology, we performed worldwide temporal (1955–2007) CMM incidence analysis by sex, age (0–14, 15–29, 30–49, 50–69, 70–85+), and skin type on 6 continents using data from the International Agency for Research on Cancer. We observe an exponential increase in the CMM incidence over time and an increase of about 2 orders of magnitude between age groups 0–14 and 15–29 exclusively in European-ancestry populations around the world independent of skin type (I–III or III–IV). Other populations like the Chinese (III-IV) had much lower CMM incidences that either remained stable or temporally decreased but did not display a dramatic increase between the youngest age groups. The dramatic increase in the incidence between the youngest age groups found only in European-ancestry populations suggests one of the most important risk factors for CMM may be developing androgenic hair, the occurrence of which appears to correlate with the distribution of CMM over male and female body sites. Besides that potential new risk factor, the increasing CMM incidence with increasing age, known not to be from cumulative UV doses, may be associated with age-related changes to skin, i.e., thinning epidermis causing lower vitamin D3 levels, and hair, i.e., whitening from higher reactive oxygen species. The temporal exponential increasing CMM incidence in European-ancestry populations may be due to Human Papilloma Virus infection of follicular hair melanocytes, found in CMM biopsies.

All sites but skin cancer incidences analyzed worldwide by sex, age, and skin type over time (1955-2007), advancing age, and UVB dose reveals important carcinogenic drivers

“…We previously described the Fitzpatrick skin type [58] designations for the populations in the different countries, the latitudes and UVB doses used, and the details of the method of analysis. [12,51,52] Quality control involved an assessment of the validity, completeness, and comparability of the incidence data, the details of which IARC provides online. [57] The IARC cancer incidence data includes all tumor stages, thicknesses, histological subtypes, and body site locations.…”

“…The only country added into this analysis that was not included in our previously published studies [51,52] is Thailand where we analyzed over time, advancing age, and UVB doses for skin type III-IV populations in Bangkok (13. …”

“…[49] Persistent HPV infection is responsible for over 90% of cervical and anal cancers, around 70% of vulvar, vaginal, and oropharynx cancers, and over 60% of penile cancers the rates of which vary by race and ethnicity: Hispanics and blacks > whites > Asian and Pacific Islanders. [50] If a cancer is steadily increasing over time beyond what genetic inheritance predicts, like cutaneous malignant melanoma, [51,52] that may indicate HPV infection is involved because its incidence has been documented to be increasing dramatically over recent decades in Europe [53] and in the United States (US). [7] However, depending on the type of cancer, the increasing incidence over time could be due to the spread of other infectious diseases like herpesviruses (EBV and KSHV), polyomaviruses (SV40, MCV, BK, and JCV), hepadnaviruses (HBV), flaviviruses (HCV), defective viruses (HDV), retroviruses (HTLV-I, HTLV-II, HIV-1, HIV-2, HERV-K, and XMRV), and bacteria, like H. pylori, S. typhi, S. bovis, Bartonella, and C. pneumonia, as well as protozoa, like P. falciparum, and parasites like trematodes, like S. haematobium, S. japonicum, S. mansoni, O. viverrini, O. felineus, and C. sinensis.…”

“…[7] However, depending on the type of cancer, the increasing incidence over time could be due to the spread of other infectious diseases like herpesviruses (EBV and KSHV), polyomaviruses (SV40, MCV, BK, and JCV), hepadnaviruses (HBV), flaviviruses (HCV), defective viruses (HDV), retroviruses (HTLV-I, HTLV-II, HIV-1, HIV-2, HERV-K, and XMRV), and bacteria, like H. pylori, S. typhi, S. bovis, Bartonella, and C. pneumonia, as well as protozoa, like P. falciparum, and parasites like trematodes, like S. haematobium, S. japonicum, S. mansoni, O. viverrini, O. felineus, and C. sinensis. [54] In previous studies, we analyzed cutaneous malignant melanoma over time all over the world [51] and also over personal UVB dose in Europe [52] and found an exponential increase in the incidence from 1955 to 2007 for only people of European ancestry. We speculated a viral infection like HPV might be involved because the rate only began to increase significantly over time, and increased with decreasing personal UVB dose only after 1960, implying increasing time indoors causing low levels of vitamin D 3 may be promoting infection.…”

“…[55] Our recent analysis of melanoma incidences around the world provided evidence that HPV persists in immune privileged androgenic hair follicles where melanocytes, keratinocytes, and stem cells reside. [51] In fact, HPV may be able to hide in many other immune privileged sites throughout the body: (fetus), brain, eye, mucosa, gut, testis, liver, skin, lymph node, and tumors. [56] We reasoned that if the majority of cancers are actually caused or promoted by HPV, then we would expect to see "fingerprints" of its involvement such as increasing incidence over time, age, estrogen (comparing male and female incidences over age), and decreasing UVB doses (lower vitamin D 3 levels).…”