I EUGENE GARFIELD INSTITUTE FOR SCIENTIFIC INFORMATION I 3S01 MARKET ST, PHILADELPHIA, PA 19104 All Sorts of -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. sufferers usu- ruses are generally species specific, that is, ally are embarrassed by them, and those each 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 , 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 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 . 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 , 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. This disease is characterized by produced papillomas in humans, cattle, and mow plasma cell tumors and overproduc- dogs. Shope also exhibited the contagious tion of monoclonrd immunoglobulins. 10In nature of these warts by transferring the in- humoral immune responses, immunity is fection to domestic rabbits. lb These papil- mediated by antibodies produced by B cells, lomas are called Shopc papillomas. or B lymphocytes, which are derived from Two years later Peyton Rous and J. W. bone marrow. This differs from cell-medi- Beard, Rockefeller Institute for Medical ated immunity, where the immune responses Research, New York, observed that benign, are controlled by T cells, or T lympho- virus-induced rabbit pttpillomas (Shop pap cytes. 11 illomas) may become malignant papillomas, which in turn can progress to squamous cell carcinomas. pigmented papillomas are the MikStOIN9 in Wart Research most likely to become malignant. IT Rous Celsus was the frost to discuss warts. in shared a Nobel Prize in 1%6 for discovetig 25 AD. In 500 AD Greek and Roman phy- tumor-inducing viruses, a major landmark sicians wrote about genital warts, which ap- of modern medical science. parently were quite common. They were the Ciuffo’s findings were not corroborated first to note the sexual transmission of gen- until 1949, when Maurice J. Strauss and col- itfd w*.4 (p. 5) At that time, however, at- leagues, Yale University School of Me& tention obviously was centered more on tine, New Haven, Comecticut, using an

61 IK#%virusi. ]

83-1825 thymoma, and othei 85.5545 82.1625 Tumors in horsm ‘ tumors in animals Effect$ of isolation, cloning, 3/16 2/16 immwwsuppression on 86.349S mdeotide SW%-?.%, production and Bleomycin, , genettc organization, proliferation of zwh~mm and other treatmmk 84.2437 and oncepwic potontial 83-565i / cells and papillnmwinms of viral warts Role of papillomavirus of human and othw Paprllamawrus- 2/19 / m g=mitalwarts and 3/1 1 papillomavirusm induced diseaams neoplasiai 11/69 22/1 55 n 22/1 95 L S.5.2974 a6.2951 Papillomavirus Humm papillomavirus associated with hum.? and cewical n@as;8 241254 20/1 66

. . atthe bottom OF each box.- electron microscope, obsemd virus-like the article by Lutzner and coworkers that bodies in samples taken from skin papillo- we identified earlier. mas. la This paper has been cited nearly 70 times since 1955. One year later, Strauss and Tracking Wart Research coworkers identified HPV as the cause of warts. l’3Thus far, the paper reporting these Figure 1 is a historiograph of the research findings has been cited about 50 times since on papillomaviruses from 1982 to 1986. 1955. However, we’ll soon know its impact Several key authors mentioned earlier have between 1950 and 1954 when we publish the published papers that are core to these top- Science Cition I&@ for 1945-1954 later ics. Research front #83-585 1, ‘‘Papilloma- this year. virus-induced diseases including laryngeal After this classic finding, research focused carcinoma, epidermodysplasia, and cervical on the causes of the different types of warts. condyloma and intraepithelial neoplasia, ” Evidence indicated that the same virus was has zur Hausen among its 22 cited core au- responsible for all types. It was not until thors. There were 155 papers published that 1977 that Lutz Gissmann, Herbert IWster, year that cited 1 or more of these papers. and Harzdd zur Hausen,zo Institute for When we performed our annual co-cita- Clinical Virology, Friedrich Alexander tion clustering exercise in 1984, this topic Erlangen-Nuremburg University, Erlangen, was easily identified and named “Role of FRG, and, independently, Orth and co- papillomavirus in genital warts, cervical workers 1 demonstrated that there is more cancer, and other neoplasias” (#84-2437). than one type of HEW. Four core papers carried over into the new The Gissmann paperzo received nearly 1984 cluster. The most-cited core paper for 140 citations from 1977 to 1987. Orth’s ar- this topic is the paper by M. Diirst, Institute ticlezl also was cited in more than 100 for Virology, Freiburg in Breisgau Univer- publications during the same period. The sity, FRG, and coworkers.zs Remarkably, two classic papers were already core articles this 1983 Proceedings of the National in the 1982 research front on “Isolation, Academy of Sciences of the USA article has cloning, nuckmtide sequence, genetic orga- already been cited in more than 210 papers. nization, and oncogenic potential of human In this study, HPV- 16 was identified as the and other papillomaviruses” (#82-1625). most prevalent HPV type found in malig- Two other papers by Orth and co- nant tumors of the uterine . Both workerszz.zJ and another authored by Gissmann and zur Hausen are coauthors of Gissmann and zur HausenzAare among the this paper. 11 core documents of this 1982 cluster. In- By tracking the core articles that we iden- terestingly, Ordr is one of the coauthors of tify each year, we can follow the twists and

62 turns of the literature. In 1985 there were Papillomavirus about 170 articles published on’ ‘Papilloma- in renal virus associated with human cervical can- allografi 7565 recipients extravasion cer” (#85-2974). Diirst, Gissmann, and zur 2/1 5 Hausen were among the 20 core authors in Treatmrmt of warts this cluster. There are two other core papers 2/1 1 worth noting. The first is by C. P. Crum, Columbia University College of Physicians and Surgeons, New York, and coworkers (including Gissmann).~ M. Etoshart, Insti- antibiotics tute for Virology, Freiburg in Breisgau 5/56 University, and colleagues (including Hsrpss simplex Gissmarm and zur Hausen) published the virus ~,36 w second .27 The Cram article, which has been cited more than 100 times from 1984 Figure 2: Multidinrensiormlly scsfed map for C2-level to 1987, identified HPV-16 in cervical neo- research tint #S6-0S25, showing links between 1986 Cl-level fronts dealing with papillomaviruses. plasms. The Freiburg paper has been cited Numbers of mrekiting papers for each C 1 front are in more than 120 publications during the shown atk the nsnre. same period. Anew type of papillomavims DNA (HPV- 18) was isolated from rnsdig- papillomas.ss It is also necessary to add to nant cervical cancer spedmens. the list Bowenoid papuleg and Bowen’s dis- In 1986 over 250 papers were published ease of the external genitalia (which are pap on “Human papillomavims and cervicrd illomavims-associated genital lesions con- neoplasia” (#86-2951). ‘This is the largest sidered to be preumcerous and which may of the warts-related annual clusters. Of the evolve into invasive cancers but which are 24 core papers identified, 3 are by not warts per se) and cervical intraepithelkd G1ssmann,2B-m2 by l%ster,sl.sz and 2 by neoplasia, so-called atypicrd Condylomas.z zur Hausen.33.34How these research fronts Each type has its own distinguishing char- are related to the topic of cancer and warts acterktics.’$ (p. 18-20) The types of warts will be discussed later in the section on can be grouped into two general categories: “Malignant Transformation. ” those affecting the skin and those found on contiguous mucous membranes.5 Each HPV type seems to cause a char- How the Rewmrciz Areas Are Related acteristic clinical manifestation. This hy- pothesis was first proposed in 197721 and Figure 2 is a C2-levei map showing the later confirmed in 1978.22 Yet, as T.F. links between Cl-level research fronts that Mrwzkowski and C. McEwen, Tulane Uni- deal with papillomaviruses. Two of these versity School of Medicine, New Orleans, 1986 fronts, points 7565 and 2951, were dis- Louisiana, indicate, certain warts have been cussed earlier. Another, 5033, will be found to contain more than one type of discussed later. The others concerning treat- HPV.36 Approximately 50 types have been ment will be covered in Part 2 of the essay. identified. However, new HPV types ccm- tinue to be discovered. K.T. Smith and M.S. Campo, Papillomavirus Research Group, BiAgicd and ‘chid ~fUSk&iti031S Beatscm Institute for Cancer Research, Glasgow, UK, explain how HPV types are As Gissmann noted, clinically there are distinguished from each other. The classi- a variety of different types of warts: com- fication is based on the lack of significant mon warts, pkmtar wruts, mosaic warts, nucleic acid homology between different plane warts, anogenital warts, lesions (for virus types. The viral DNA is composed of example, brownish or reddish macules or two strands with complementary (homolo- papules) in EV patients, and laryngeal gous) nucleotide sequences. In distinguish-

63 Table 1: Types of warts and associated HPV types.

Frequently Asscxiated Common Site(s) Type of Wan HPV Type(S) of Appearance

Common wart HPV- 1 Hands (verruca vufgaris) Mosaic warts HPV-2 Soles and Im9s of feet; palms; knuckfes; armmd fingernails Plane wana (flat HPV-3, HPV-10 Face; arms; backs of hands of Aih&en and young women warra, vet-mea plana) Plantar Warta HPV- 1 Plmtar surface of foot (verruca plantaris) Butcher’s warts HPV-7 Hands of butchers, poultry workers, veterinarians Anogenital warts HPV-6, HPV-11 External mucoml surface of genitatia; anore$tid area of both men and women; lower genitaf tmct of women Epidenrmdysplasia HPV-3, HPV-5, HPV-8, All parts of Skin verruciformia (EV) HPV-17, HPV-20 Laryngeal papiflomas HPV-6, HPV-11 Vomf cords and larynx of chifdren and some adults

Genital intmeiithelial HPV-16. HPV-18. Sanre as time for anogerdtal warta neoplasia HPV-il , HPV-33 ing HPV types, a viral isolate is considered urethra, bladder, and oral cavity, note Alex- to be an independent virus type if it shares ander Meisels and Carol MOM, Saint- less than 50 percent of nucleic acid Sacrement Hospital, Quebec, Canada.sg homology with other papillornaviruses.sT aggravates genital warts, caus- Table 1 shows the links between different ing them to become larger and multiply. HPV types and the different kinds of warts Genital warts generally are seen in sexual- they produce. ly active adults. When condyloma acumi- Verruca vulgaris, or the common wart, nata are found in children, sexual abuse is the most frequently encountered wart, should be suspected, although children with and, whiie found most often on the hands, hand warts can spread the infection them- it actually can appear anywhere on the skin. selves, or a caretaker with warts could un- Mosaic warts, which are very resistant to intentionally infect the child. However, a treatment, are typically seen on the soles and physician should look for further signs of heels of the fest and on the hands. Plane sexual abuse in these cases.s warts appear most often on the backs of A very rare skin disease, EV, mentioned hands of children and young women, but earlier, is characterized by generalized plane rarely on those of men. They usually are warts and other flat lesions. In 1972 Stefania multiple and increase in size and number Jablonska and coworkers, Warsaw School before disappearing. Painful plantar warts of Medicine, Poland, reported on a study often occur in young adults on the pressure showing that HPV is responsible for the points of the plantar surface of the foot. cutaneous lesions in EV and does not sim- Condyloma acuminata (genital warts), cer- ply accompany them.sg More than 15 HPV vical flat condylomas, and genital intraepi- types, among them HPV-3, -5,-8,-17, and thelial neoplasia grow on the genital muco- -20, are associated with this condition (Table sa. Genital condyloma acufninata usually oc- 1). These warts can undergo malignant cur on the penis and sometimes on the transformation when exposed to sunlight. In , anus, , , and cervix. fact, HPV is necessary for the initiation of Occasionally, condyloma acuminata appear this process.w (More will be said about this on extragenital locations such as the nipple, later.)

64 Laryngeal papillomas, which grow on the specific types of papillomaviruses can de- vocal cords and larynx, affect children and velop into specific malignant tumors. He adults and can obstruct airways. While they also poshdated that one papillomavirus alone are seen as frequently in both groups, they is not capable of triggering malignant con- are more distressing in children.z Emer- version. In order for a papilloma to become gency surgery usurdly is required. Unfor- a carcinoma, an interaction with some type tunately, these warts often recur. M.E. of chemical or physicrd carcinogen is neces- Bender, Department of Dermatology, ~ .43 Mr~~kowski ~d McEwen ~lieve University of Minnesota Medical School, that there is a multiple-factor relationship be- Mimeapolis, explains that HPV-induced tween hereditary disposition, susceptibility warts and tumors may reappear atler all clin- to papillomavirus, and possible changes in ically detectable signs of warts are removed cell-mediated immunity caused by rdtravio- because latent HPV DNA apparently can Iet radiation.qb However, not all papillomas persist in susceptible cells for several months subjected to these influences will become without showing any signs of recurrence. If malignant. all of the HPV infection is not removed or Smith and Carnpo, in their article in An- destroyed, then the dormant HPV can ticancer Research, indicate that conversion become active and stimulate wart growth at of human papillomas into squamous cell car- a later time.~ cinomas has been seen in people with EV, There seems to be a connection between laryngeal papillomas, and anogenital con- laryngeal warts in children and genital warts dylornata.3T Normal warts generally do not in mothers at the time of their deliveries.d become malignant. However, Shelley, men- (p. 20).S D.J. McCance, Department of tioned earlier, and Margaret G. Wood, Microbiology, United Medical and Dental University of Pemsylvania School of Schools of Guy’s and St. Thornas’ Hospi- Me&cine, reported the fust case of a patient tals, London, postulates that the virus may in whom common warts repeatedly under- be transmitted to infants in aspirates (fluids went malignant change over a period of in the womb that the baby may inhale) dur- years.~ Malignant transformation of plan- ing vaginal deliveries in women who have tar warts and common hand warts that are genital wart infections.41 caused by HPV- 1 and -2 or -4, respective- ly, is unknown. Flat subclinical warts are Malignant Transformation the most dangerous because they do not look like warts. However, they are the ones with Unfortunately, some benign warts, in- the greatest malignant potential. Bumey, cluding genital and laryngeal papillornas and mentioned at tie onset of this essay, pointed the genital HPV-associated lesions known out that not every individual who carries the as intraepithelial neoplasia (Bowenoid poten~ial carcinogenic virus will develop papulosis, Bowen’s disease, and cervical in- cancer.ds traepithelial neopiasia) have the potential to become malignant. Normrd skin warts are Variable HPV Potential generally harmless. However, some benign lesions in both humans and animrds can Individual HPV types have different on- undergo malignant transformation, also cogenic potentials. HPV- 16 and -18 exhib- refened to as malignant conversion. In 1980 it the strongest links to genital cancer. In Orth and coworkers were the first to de- fact, HPV- 16 is the most striking example scribe a connection between warts and ma- of viral specificity for malignant tissue. 37 lignancy. They found HPV-5 in squamous HPV-5, -8, -16, -18, -31, and -33 are the cell carcinomas in EV patients .42 This ar- most likely virus types to undergo malignant ticle has already been cited in 150 subse- transformation.qb EV patients seem to be at quent publications. especially high risk of developing skin According to zur Hausen, who also inves- cancer. HPV-5 is the most likely HPV type tigated the link between HPV and cancer, involved, converting the papillomas to .-.

65 squamous cell carcinomas. The carcinomas Gissmann and zur Hausen characterized appear predominantly on areas of the body HPV-6 as the most common HPV type that exposed to the sun, although some have also is found in condylomata acuminata. The been found on unexposed skin. 1980 article describing their work was one Warts of renal allograft patients also are of the core papers in #82- 1625 and has been susceptible to malignant transformation. cited 70 times thus far.zd In a 1983 paper HPV-5 is implicated in these individuals as Gissmam and colleagues reported on their well. Lutzner was the first to uncover findings ofHPV-11 DNA in condylomata HPV-5 in renal allograft patients. s Until of the cervix. ~ This article is core to this discovery, the virus had been seen only research fronts #84-2437, #85-2974, and in EV patients. #86-295 1 (Figure 1). Laryngeal papillomas caused by HPV-6 Existing evidence indicates that both men and -11 rdso can become malignant. These and women with genitrd HPV infections are papillomas in children were usually treated at risk of cancer. Those with HPV-6and -11 with X rays until it was discovered that the infections are at low risk, while those with X-ray treatment led to mrdignant conversion HPV-16, -18,-31, and -33 are at high risk. later in life.ds Apparently, there is some Smoking and virus infec- type of synergism between HPV infection tions, according to zur Hausen, maybe the and X-irradiation. Twenty percent of laryn- “initiating” events that lead to genital n3alig- geal papillomas in adults undergo malignant nant tradormation. 43We’ve identified one transformation. Heavy smoking seems to be small research front, “Herpes simplex a contributing factor here. virus” (#$6-5033), relevant to this topic A group of HPV types is involved in (Figure 2). genital cancers and may be sexually trans- This concludes Rut 1 of this essay. We’ve mitted since they are found in benign and discussed the different types of warts, their malignant lesions in both men and women. etiology, and their potential transformations. Cervical lesions are the most common mrm- The ccmluding part of this review will cover ifestations of sexually transmitted HPV in- ancient and modern treatments as well as fections in women. Meisels and Morirr were spontaneous regression of warts, when for the first to note the frequent coexistence of some unknown reason they disappear by condylomata caused by sexually transmit- themselves. We’ll also identify the journals ted HPV and dysplasia and neoplasia in cer- that publish most of the literature on this vical squamous epitheliums.38In a 1986 ar- multidisciplinary problem. ticle, Philip G. Toon, North Manchester General Hospital, UK, and colleagues ***** reported an association between HPV-16 and both cervical intraepithelird neoplasia and cervical cancer.% HPV- 16, -18, -33, My thanks to Terri Freedman and -35, and -39 are the most frequent HPV Mananne i!hjdel for their help in the types associated with malignant genital preparation of this essay. cancer. O:mm

ru2FERmm

1. Viral infections of the skin. (Berkow R, cd.) 7he Merck manual of diagmti and therapy. Rahway, NJ: Merck Sharp & Dohnw Research Latmmtorics, 1987. D. 2274-7. 2. Ortb G. Pcrwr@l communication. 2S Jan~ 198S. 3. PapiJJoma. (Landau S 1, cd,) Intemuicmal dictionary of medicine and biofogy. Ncw York Wiley, 19S6. Vol. 3. p, 2073. 4. Buemey M H. Vimf warts: rhtir biofogy and treamk?m.Oxford, UK: Oxford University Press, 1982, 99 p. 5. Ceflfs S J%.W@ and IIKIIIUSCUMmntasiosurn in children. Pedti. ,4JUI.1669-76, 1987. 6. Kfdmer H. Immunabiology of human papillomavirus infection. Prog, Mat Vii-d. 33:1<1, 19S6. 7. Sbeky W B. Personal communication. 4 Febmary 1988.

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