BACKGROUND: Cancer is a significant and growing problem worldwide. While this 
increase may, in part, be attributed to increasing longevity, improved case 
notifications and risk-enhancing lifestyle (such as smoking, diet and obesity), 
hygiene-related factors resulting in immuno-regulatory failure may also play a 
major role and call for a revision of vaccination strategies to protect against 
a range of cancers in addition to infections.
DISCUSSION: Human endogenous retroviruses (HERVs) are a significant component of 
a wider family of retroelements that constitutes part of the human genome. They 
were originated by the integration of exogenous retroviruses into the human 
genome millions of years ago. HERVs are estimated to comprise about 8% of human 
DNA and are ubiquitous in somatic and germinal tissues.Physiologic and 
pathologic processes are influenced by some biologically active HERV families. 
HERV antigens are only expressed at low levels by the host, but in circumstances 
of inappropriate control their genes may initiate or maintain pathological 
processes. Although the precise mechanism leading to abnormal HERVs gene 
expression has yet to be clearly elucidated, environmental factors seem to be 
involved by influencing the human immune system.HERV-K expression has been 
detected in different types of tumors.Among the various human endogenous 
retroviral families, the K series was the latest acquired by the human species. 
Probably because of its relatively recent origin, the HERV-K is the most 
complete and biologically active family.The abnormal expression of HERV-K 
seemingly triggers pathological processes leading to melanoma onset, but also 
contributes to the morphological and functional cellular modifications 
implicated in melanoma maintenance and progression.The HERV-K-MEL antigen is 
encoded by a pseudo-gene incorporated in the HERV-K env-gene. HERV-K-MEL is 
significantly expressed in the majority of dysplastic and normal naevi, as well 
as other tumors like sarcoma, lymphoma, bladder and breast cancer. An amino acid 
sequence similar to HERV-K-MEL, recognized to cause a significant protective 
effect against melanoma, is shared by the antigenic determinants expressed by 
some vaccines such as BCG, vaccinia virus and the yellow fever virus.HERV-K are 
also reactivated in the majority of human breast cancers. Monoclonal and 
single-chain antibodies against the HERV-K Env protein recently proved capable 
of blocking the proliferation of human breast cancer cells in vitro, inhibiting 
tumor growth in mice bearing xenograft tumors.
SUMMARY: A recent epidemiological study provided provisional evidence of how 
melanoma risk could possibly be reduced if the yellow fever virus vaccine (YFV) 
were received at least 10 years before, possibly preventing tumor initiation 
rather than culling melanoma cells already compromised. Further research is 
recommended to confirm the temporal pattern of this protection and 
eliminate/attenuate the potential role of relevant confounders as socio-economic 
status and other vaccinations.It appears also appropriate to examine the 
potential protective effect of YFV against other malignancies expressing high 
levels of HERV-K antigens, namely breast cancer, sarcoma, lymphoma and bladder 
cancer.Tumor immune-therapy, as described for the monoclonal antibodies against 
breast cancer, is indeed considered more complex and less advantageous than 
immune-prevention. Cellular immunity possibly triggered by vaccines as for YFV 
might also be involved in anti-cancer response, in addition to humoral immunity.