I EUGENE GARFIELD INSTITUTE FOR SCIENTIFIC INFORMATION I 3S01 MARKET ST, PHILADELPHIA, PA 19104 All Sorts of Warts-Separating Fact from Fiction. Part 1. Etiology, BRology, and Research Mikstones L A Number 9 February 29, 1988 Warts are common,contagious,usually benignepithelialpapillomascausedby the humanpapillo- mavirus.In Part 1of this two-partessay, the etiologic,biologic,and clinicalcharacteristics,as well as msdignaattransformationin warts, are discussed.Usingthe ISI@databaw, we’veidentifiedthe most activeresearchfrontsduringthe past decadeand their relationshipto other medicalproblems. Thekeyplayersin thisinternationalfieldincludeG&d Orth,LutzGissrmmrs,andHarsldzurHausen. Milestonepapers and CitorionCskrsics” commentariesalso are discussed.Pam2 will cover treat- ment and spontaneousregression. We’ll also list the jourrudsthat publishwart research. For some reason there has always been Description a certain mystique about warts. I can re- member as a child hearing a lot of old wives’ Warts are common, contagious, usually tales about how people got warts. According harmless epithelird tumors caused by one of to one of the more popular theories, the human papill.omrwiruses (HPVS), mem- touching a toad or frog would cause warts bers of the family Papovaviridae. 1 Papillo- to grow on your hands. trtavirttses infect humans and a number of There are a lot of misconceptions and mis- animals, including rabbits, sheep, cattle, understandings about those strange bumps horses, dogs, monkeys, and deer. The vi- that appear on the body. Wart sufferers usu- ruses are generally species specific, that is, ally are embarrassed by them, and those each virus will infect only a specific target without warts generally are repulsed by host. (One exception, however, is bovine them. Unfortunately, even among the edu- papillomavin.ss, which has a larger host cated, few realize that warts, like the com- range than other papillomaviruses and can mon cold, are caused by a vims. By con- infect horses, hamsters, and rats, aa well as trast, who is embarrassed to suffer from a cattle.) As G&ard Orth, Otrstave-RotrssyIrt- cold, even with its visible symptoms? Also stitute, INSERM, Villejuif, France, points unknown to most of the .g,eneralpublic is that out, one of the drawbacks in studying pap- these seemingly benign nuisances have the illomaviruses is that they do not grow in potential to become a serious health prob- vitro. However, the use of DNA recombi- lem. nant technology has helped researchers In this two-part essay, we are going to try partly overcome this problem.z to dispel some of the myths about warts and Papillomas, which are benign tumors, are answer some common questions. What ac- produced in their hosts by the vimses. They tually causes them? How are they best contain variable amounts of infectious virus. treated? And of greater importance to Cur- The word papilloma is derived frompupilk, rent Contents& readers, who are the leaders meaning pimple or pustule, and the suffix in wart research? As you’d expect, we’ll re- -mu, which denotes a tumor or neoplasm.s view their work and the impact they’ve had In the wart literature the terms wart and on the field. We’ll also identify the most ac- papilloma are used synonymously. Here we tive research fronts related to warts. will do the same. 59 Direct skin-to-skin contact is the most lescents, especmliy before puberty, but common means of wart transmission. The rarely in the elderly. Children under the age virus enters the skin through small surface of two are rarely affected, according to abrasions. Nailbiting, which traumatizes the Stephen E. Gellis, Tufts University Medical skin, can aggravate warts on the fingers and School, Medford, Massachusetts.s How- make them extremely difficult to treat. Sub- ever, the entire population is at risk. Genital sequent to their infection through a micro- warts are mainly seen in sexurdly active trauma, epidesmal basal cells proliferate adults. either downward, giving rise to endophytic Holger Kirchner, Institute of Virus Re- warts like plantar warts, or upward, giving search, German Cancer Research Center, rise to exophytic warts like common Heidelberg, Federrd Republic of Germany warts.z Papillomavirus infection probably (FRG), suggests several reasons for the in- occurs in the basal layer of the epidermis. creased incidence of warts in children. He Warts not only are contagious, but they also believes that a child’s skin is different from can spread from one part of the body to an- that of an adult and is more susceptible to other. For example, warts can be transmitted viruses, possibly as a result of hormonal in- to the face or feet from the hands. Children fluences. And, Kirchner postulates that some with hand warts who suck their thumbs can children may have a defective immune de- infect the facial areas around the mouth and fense mechanism before puberty and thus on rare occasions the tongue and mucous cannot fight the HPV.6 Another possible membranes. However, hand waxtsare rarely explanation for the increased incidence of transmitted to the anogenital area. warts in children may be that adults acquire Public bathing and changing facilities are immune protection after a frost infection common sources of plantar warts. The during childhood with these widespread rough, nonslip surfaces that surround many viruses.’2Dermatologist Walter B. Shelley, swimming pools and shower areas act as Medical College of Ohio, Toledo, adds that abrasives that rub infected materird off of “warts seem to be one of those universally plantar warts. Papillomavirus particles have acquired viral infections of childhood, in a very simple structure and are considered many cases not even apparent to the child to be stable. They are shed in the environ- or parent. Accordingly, the opportunity for ment inside resistant, cornified cells. In the transmission from child to child is great. The absence of in vitro studies it is difficult to clinical problem is seen in those with imm- evaluate their susceptibility to specific dis- une deficits, either genetic or acquired.”7 infectants. Thus, the use and effectiveness Injury and irritations seem to increase the of chlorine or other agents is questionable chances of contracting warts. Those in some in regard to killing and controlling the injury-prone occupations, such as butchers, spread of the virus in these areas.2 HPV fishmongers, and paltry processors, are does not survive long on objects, and, al- especially susceptible. The hands of these though it is not likely, wart infection occa- workers are constantly macerated because sionally may be picked up from contami- they are immersed in water and other fluids. nated objects, such as golf club handles at Thus, the risk is increased. Not surprisingly, rental driving ranges. the resulting warts are often called butcher’s warts. Patients with deficiencies in cell-mediated Prevalence immunity (those with AIDS, Hodgkin’s diS- Dermatologist Mary H. Bumey, Royal ease, malignant lymphoma, and chroNc Infkmary, Edinburgh, UK, points out that lymphocytic leukemia) frequently have approximately 10 to 25 percent of patients warts. Individuals taking irrtmunosuppres- who visit a dermatologist do so for warts. 4 sant drugs, particularly renal allograft re- (p. 1) Certain groups seem to be at higher cipients, are prone to widespread and resis- risk than others. Common warts are seen tant warts. A compromised immune system most often in school-age children and ado- makes it difficult for the body to fight the 60 HPV infection. Next to herpesviruses, HPV treating warts rather than discovering what infections are the most frequent viral com- actually caused them. plications affecting immunosuppressrxi in- It was not until 1891 that Joseph F. Payne, dividuals.b a physician at St. Thomas’ Hospital, Lon- don, recorded the infectious nature of warts. In his classic paper’ ‘On the contagiousness Warts and Immune Deficiencies of common warts, ” Payne described how warts grew on his own thumb after he had Related to this topic is the research front scraped off the surface of a child’s wart. entitled ‘‘Papillomavirus in renrd allograft Payne concluded that’ ‘fresh warts are pro- recipients” (#86-7565). Two articles are duced by local inoculation of some patho- core to this cIuster. One, by Marvin genic material derived from an existing Lutzner, Pasteur Institute, Paris, and col- one ~~12 Further evidence Of the conkl- Ieagues,s was the first paper to report giousness of warts was supplied in 1894 si- ftiings of skin lesions induced by human multaneously by C. Licht13 and Parisian papillomavirus type 5 (HPV-5) in two im- pediatrician Gaston Variot, 14 who experi- munosuppressed renal allograft recipients. mentrdly transferred warts to volunteers by HPV-5 had previously been found only in injecting them with ground wart tissue. patients with the rare skin disease epider- In 1907 G. Ciuffo was the first to associate modysplasia verruciformis (EV), which viruses with wart diseases. 15 In his ex- often becomes malignant. (HPV types and periments Ciuffo produced warts on his own EV will be discussed at greater length later.) hand by injecting himself with a filtrate that The second core paper, written in 1975 had been passed through a pore so small that by Warwick L. Morison, St. Helier Hospi- only viruses could be involved. tal, Surrey, UK,9 reviews results of a study Similar research was done in rabbits by of patients with immune deficiency dis- Richard E. Shope, Department of Animal orders. Morison found that patients with and Plant Pathology, Rockefeller Institute cell-mediated immune deficiency, specifi- for Medical Research, Princeton, New Cdy Ho@dn’s diWa.W,WCIE MOre SUSCi?p- Jersey, in 1933. Shope found wild cotton- tible to warts and herpes zoster infections tail rabbits with naturally occurring warts. than were patients with humorrd immune de- He found that the wart-producing agent was, ficiency, for example, those with multiple in fact, a virus much like the viruses that myeloma.