title: Spinocellular carcinoma from warts in a HPV infection natural history lasting 49 years. Virus strategy or host choice? Implications for researches and therapeutic vaccines.
abstract: There is a very strong evidence that progression (also to cancer) in variable percentages of cases infected by HPV, HBV, HCV, and HIV depends on host immune response. A large number of observations demonstrate that virus set up a postulated "active strategy" to modify host reactions or to avoid it. But in all those infections it also seems that antigen load (viral RNA or DNA), chronic activation of immune response and time elapsing from the primary infection play a pivotal role in determining clearing or persisting outcomes. My wife's HPV and cancer natural history, lasting 49 years, started at the age of 10 years with facial warts and progressed to CIN 2/3, cervical in situ carcinoma, perineal warts, perianal carcinoma, inguinal lymph nodes, and invasion of bones and muscular structures, until death is paradigmatic: a progressive immune failure was detected in her scaling up all those clinical features, ending in a massive apoptosis of her lymphocytes collected by leukapheresis and cultured with HPV antigens E6/E7, with the aim of obtaining antigen presenting cells and CD8+ specific T lymphocytes. From this experience, a concept of "host choice to reach a tolerance (mainly by a Tregs mediated anergy) or symbiotic-like state" arises, underlining all the affected host's immune-responses to virus persistence (and to consequent tumors). It might be then postulated as the hallmark of a long-term host/parasites co-evolution, and considered a "normal" reaction when the host faces overwhelming numbers of non-self cancer cells (high antigen loads) preceded by persistent virus infections (chronic activation). This happens in patients who do not clear HPV or other viruses soon enough after infection. These observations may lead to a better understanding of many phenomena that are actually difficult to explain or still are open questions. The auto-limiting host's immune-responses are likely to be aimed to avoid risks arising mainly in the protection of "self" (autoimmunity), to prolong its own survival (balance with the virus), to avoid the risk of producing uncontrolled cells (dangerous outcomes). Finally, the postulated negative implications for therapeutic vaccines in cervical cancer, as they really seem to not work till now might be ascribed just to the cited host immune-specific state itself, through an activation induced cell death, elicited by recall antigens (E6/E7 in the case of my wife). Also this latter hypothesis, as well as the previous ones may be of some value to better account for clinical behaviors and researches.
authors.affiliation: Department of Experimental Medicine, University of L'Aquila, Via Vetoio 1, 63100 L'Aquila, Italy. marc.criscione@tiscali.it
authors.forename: S M
authors.initials: SM
authors.lastname: Criscione
mesh_terms: D019496:Cancer Vaccines / Q000008:administration & dosage*; D006801:Humans; D030361:Papillomavirus Infections / Q000503:physiopathology*; D013125:Spinal Neoplasms / Q000517:prevention & control / Q000821:virology*
chemical_list: D019496:Cancer Vaccines