CONDYLOMA ACCUMINATA Social issues, cancer Treatment ---------------------------------------------------------- Dear colleagues, how catastrophic do you feel a diagnosis of condyloma acuminata is. Today I saw a very sad and confused young graduate student, remorseful about unknowingly transmitting this dread disease to his now ex-significant other, an endocrinology graduate student. He had been seen by a P.A. many times, and was totally freaked out by every hair follicle on his penis. The relationship between these two very lovely people dissolved because of this stress. The young woman was read the riot act by a nurse practioner and is having pap smears twice a year and will live with the fear of cervical cancer for goodness knows how long. I remember the old days of the Herpes Hysteria, when there were Herpes support groups every other block. How would you counsel this young man? Diane Thaler ------------ I think it is understandably devastating to a sensitive young person who, up till then, considered themselves healthy and "clean". Our job is to help without being judgemental. However, lack of knowledge and foresight is what got the young person in trouble in the first place. There may certainly be some grief over that. At the point you see the patient, they need comfort, education, and treatment, but you can not unring the bell for them. Part of treating them is to help them deal with the guilt they may feel. If a relationship is going to break up over the issue, it may have foundered later anyway. On the other hand, if a skilled practitioner can help a couple deal with issue well, and if their relationship is inherently healthy, then it might survive. I would suggest, where possible, that both partners be counselled together. This may not be possible for the couple you describe. I do not think Paps every six mo are required, but I do recommend colposcopy by a skilled gyn to check for and treat condylomatous changes on the cervix. leave it up to the gyn to determine the frequency. I have occasionally sent men to a urologist for microscopic eval of the urethra. I also advise the couple, if only one has shown sx, to use condoms until it is reasonably certain both are clear. In some cases, I recommend continuous use of condoms. Of course the infected partner still has and sheds the virus. I show men how to use vinegar at home to examine themselves, and what to look for. There is of course a danger that he may become obsessed by this search, so it is not for everyone. I do counsel on the potential hazards of cervical cancer and juvenile polyposis in infants born to mothers with active infection. I think this can be done in a non-judgemental atmosphere, answering questions along the way, and emphasizing the possibility of avoiding serious sequelae by regular exams, esp during pregnancy. Jerry Eisner ------------ Concerning the recent post from Dr. Thaler about her patient with condyloma acuminata and his concern of spreading a dread cancer-causing virus, I would like to mention the data from some recent studies that should greatly assuage his fears: (1) genital papillomavirus infections are very common. In asymptomatic sexually active young women, the prevalence of infection exceeds 20% when assessed by sensitive PCR-based viral DNA measurements. Most of these infections are transient and become undetectable within a year or two. Recurrence is often observed, but the proportion of recurrence caused by reinfection vs. reactivation of a clinically latent infection is unclear. (2) The vast majority (>95%) of condyloma acuminata lesions are caused by HPV 6/11, with HPV 54, 58 less common. THese are low-risk viruses in terms of their oncogenic potential. Patients with detectable HPV 6/11 DNA have no higher risk than HPV 6/11 DNA -ve controls for having cervical cancer. In contrast, the relative risk that patients with detectable HPV 16 DNA have cervical cancer is 260, compared to HPV 16 DNA negative controls. (3) Patients with detectable HPV 6/11 DNA have a thirty-fold increased risk for high grade squamous intra- epithelial lesion (HSIL), compared to HPV 6/11 DNA negative controls. Present dogma regards HSIL as a likely precursor lesion to cervical cancer, and the standard of care is to destroy the lesion. However, given the information cited above, it is quite likely that a substantial fraction of HSIL would spontaneously resolve. Epidemiologic studies to resolve this are, understandably, ethically problematic. The point I'm trying to make is that there is a substantial downside to aggressive screening in young women--you will probably destroy many lesions that would spontaneously resolve to catch a cancer. Obviously, the key is to target PAP smears for susceptible populations. (4) Present ACOG recommendations for PAP smears are: q 1 to 3 years at onset of sexual activity, D/C at 65 if consistently normal. There is no reason why the patient's ex-girlfriend in this case should have screening any more frequently than according to ACOG recommendations. These guidelines probably result in the overscreening, and overtreatment, of young women, for whom the incidence of cervical cancer is extremely low (15-20 year olds, 1987 U.S. SEER data, 0.3 per 100,000). In comparison, 70-75 year olds, 1987 U.S. SEER data, 17.5 per 100,000. Cervical cancer is an old person's disease--40% of deaths occur in people older than 65. 50% of cervical cancers occur in women who have never been screened, 60% occur in women with no smear within the last 5 years. So the giant failure from a public health perspective is our poor job of screening the elderly. (5) There is good news on the horizon. Within the next few years, screening for the oncogenic HPV types through DNA detection of cervical material will enable us to decrease the frequency of PAP smears for patients who are consistently high-risk DNA negative. Women who are consistently high-risk DNA positive will get increased frequency of PAP smears. Epidemiologic studies to verify that this is a rational strategy are underway. There are also promising vaccine strategies, both for prevention and treatment. Marty Okun Bethesda, Maryland ------------------ I would strongly argue with the approach listed here, suggesting the sub-clinical cervical disease in the absence of dysplasia needs to be treated, with similar suggestions for men as well (the "androscopy" concept with acetowhitening of the penis and magnification examination). It is a complex issue which I addressed in detail in an article in the IJD several years ago, but suffice it to say that: 1. It has NEVER been shown that any form of treatment of such subclinical disease of the cervix can be effective. Even reports of viciously aggressive total cervical/vaginal CO2 laser were uniform in showing extremely high recurrence rates within months of treatment. This is a PERMANENT viral infection, despite our desires to "eradicate the virus." 2. Even if such subclinical disease is treated, there is no evidence that this alters the course of the disease between partners. Specifically, see reports where women with abnormal Pap smears were randomized to treatment, along with or without aggressive acetowhite screening and treatment of subclinical and clinical lesions in their male partners. Both groups had identical success rates of treatment in the women: the concept of "ping-pong" reinfection between partners appears to be a fallacy, again consistent with the concept that the viral infection, once established, is permanent. I think the problem of advising treatment of HPV infection is that it is often fruitless and contributes greatly to the patient's sense of hopelessness. Treatment should be reserved for the disease (cervical dysplasia) where it is very successful, not for the viral infection which is in most cases asymptomatic. Mark Ling, M.D., Ph.D. ---------------------- I gladly accept your wisdom on these points, Mark. This goes along with the tenor of Marty Okun's note on the subject., also. Questions remain: How do you counsel a young person on the personal risks and follow-up for him/her and the partner? And regarding future partners? How does the physician go about follow-up, if any, for condylomata? Is there any reason to treat at all except for appearance? Are men different than women in any regard other than the need for Paps? What do you counsel a couple where only one person has clinical disease and the other has no clinical diagnosis yet? Is virus typing of any current value clinically? And is it feasible in the average office? How do you deal with the emotional impact of this condition on the patient and partner? Jerry Eisner MD --------------- I appreciate what Mark Ling was saying in his May 8th post about HPV latency and the difficulty of eradicating all viral DNA from the cervix. However I still clincally detectable warts will shed the largest infectious particle loads and the spread of the disease to uninfected areas both in self and partners can be avoided or minimized by eliminating these, even if getting rid of all latent viral DNA from previously involved areas is problematic. My guess would be that shedding of infectious particles from latent areas _without_ visible warts is minimal compared with clinically diagnosable warts. Also, if you don't treat the clinical lesions aggressively, you will probably have many more areas of latent viral DNA that then have some potential to give rise to tumors, depending on wart type. My experience is that if you are persistent and aggressive, it is possible to get patients to the point that they have no recurrences of clinically evident warts, or at least very few recurrences of clinically detectable warts. To stand back and do (almost) nothing is a nilest approach that will increase the suffering of patients and their partners--e.g., prolong the duration and number of clinically evident lesions. The risk of cervical cancer is real, and if a few people get bent out of shape about this, maybe they should. I do agree that once you have dealt with all clinically detectable lesions, that Pap smears in women as per COG recommendations (every 1-3 years) is the best long-term measure to take. Mark Naylor, M.D. ----------------- Many difficult and very important questions. Regarding the first question, I'll make one comment: if HPV-related dysplasia were as common, and as medically worrisome in men as it is in women (as has been claimed on occasion) I am then mystified why I am not seeing an epidemic of penile SCC's (outside of the HIV+ population). I have seen it maybe once in 10 years (not bowenoid papulosis etc, but true invasive SCC). Therefore I do not do anything routine to screen for disease a la Pap in females. I'd be very interested in comments from Jerry and the group. Mark Ling, M.D., Ph.D. ---------------------- Agreed that genital warts have a different biology in males than females, probably because (especially circumcised) men have dry, glabrous skin on the penis, not the squamo-columnar epithelium present in the cervix. This seems to protect men from the worst problems of viral carcinogenesis. Although HPV sequences are present in a substantial percentage of SCC of the penis, penile cancer seems much less likely an outcome in men infected with warts than in women infected with warts (e.g., cervical cancer). The cervical cancer problem, on the other hand is very real; witness the fact that 80 or 90% or better of cervical carcinomas have HPV DNA sequences in them. Latent DNA in the cervix is best dealt with by following with Pap smears until we have better technological means to deal with this problem. I have not been impressed that the vinegar approach to finding subclinical warts in men is not very productive. I think a skilled examiner is the most important thing, along with an aggressive attitude towards treatment of clinically evident lesions. By the way, I think condoms and/or abstinence for several weeks until the clinically evident lesions are dealt with is an excellent idea that I actually recommend to patients. Since we don't know clinically which condyloma are high risk, we should treat them all the same (aggressively) while highly infectious clinical warts are present. Even if almost none of the warts we treat are high risk, we still have to treat aggressively unless we want these things to spread to the point that every sexually active adult has them. If all physicians take the old nihilist approach to genital warts that was so prevalent 20 years ago, we'll see the incidence of this problem skyrocket. Come to think of it, maybe that's just what happened and now we are paying the price for what physicians did (or more precisely didn't do) 20 years ago. Mark Naylor, M.D. ----------------- Sorry if I was misinterpreted: I certainly do recommend treating macroscopic lesions, for many reasons, most importantly in hopes of reducing viral burden and possibility of transmission. It's only when we get into subclinical "acetowhite" lesions that my nihilistic side starts to emerge. Mark Ling, M.D., Ph.D. ---------------------- I have only seen one penile ca in my twenty years of medical practice. One case of severe juvenile polyposis requiring tracheostomy. Only a couple of true cervical cancers and several in-situ cancers. The other issues occur on a weekly basis. Saw one today just before lunch. Couldn't be sure anymore, since our discussion, whether to advise this young man to use vinegar whitening on himself to screen for new lesions. Partner is not my patient so don't know if she has infection. I suspect active lesions spread disease better than normal appearing skin. When he asked, I told him that oral sex could very likely be expected to spread the virus to mouth or skin. Jerry Eisner MD ---------------- I suspect that since external penile lesions are usually spotted and removed they don't get the chance to evolve into SCCs. Guy Webster ----------- Dr.Webster, your comment reminded me of a recent patient, 37 year old celtic male with a 2cm squamous cell ca on the very proximal shaft in the exact are where he remembers a wart being treated years ago. I do not know what variety it was. Clinically this was definitely not Bowenoid Papulosis. He opted for Mohs. Diane Thaler MD --------------- Having untreated clinical lesions of any kind in the genital area puts the patient at increased risk for acquiring additional STDs, due to there being "abnormal anatomy" at the site, and thus the intact cutaneous border is broken. These additional STDs include the less common carcinogenesis-related HPV particles and HIV disease. T. Keith Vaughan, M.D. ---------------------- How would one treat a 54 year old woman with apparent very extensive peri-anal condyloma accuminata which were removed surgically by a competent general surgeon and reported as Bowen's Disease extending to the edge of the sections. Clinical examination shortly after the procedure showed only diffuse erythma.He plans to scope her soon. Any suggestions from the group? Multiple biopsies? Moh's? 5-fluorauracil? etc?? Wiliam Gerstein MD,FRCPC -------------------- Consider interferon plus aromatic retinoid. I can find the studies if you are interested. Diane Thaler -------------------- Dr. Gerstein is describing a classic example of Bowenoid Papulosis. These can resemble small condylomatous papules, and the peri-anal location is a common location (1). Histologically, they show as much cellular atypia as Bowen's disease. HPV 16 and/or 18 have been found in about 80% of these lesions, and cervical dysplasia may also be present. The sexual partner may have similar lesions. Without treatment, persistence, progression or invasive cancer may occur although spontaneous resolution (as with other HPV-related dermatoses) is common. They rarely recur after conservative (shave) excision and fulguration, and other destructive modalities are helpful as well. I had a similar patient whose lesions disappeared after one session of Liquid Nitrogen treatment, and, with regular follow-up, the lesions did not recur. I would think that 5-Fluorouracil would be effective as well. Of course, if the presenting lesion, instead of small individual papules, was a larger plaque and the histologic changes were Bowenoid, then Bowen's disease would be the diagnosis and the scope would be indicated. 1. Arnold HL, Odom RB, James WD. Andrews' Diseases of the Skin. Philadelphia: W.B. Saunders Company, 1990:472. T. Keith Vaughan, M.D. -------------------- they're probably bowenoid papulosis, #16, 18, 30, 31...if they can take it efudex works nicely... steve emmet -------------------- I think all of your ideas could be useful: Multiple biopsies? Moh's? 5-fluorauracil? Consider Cyndylox (Condyline) once or twice a week prophylactically. And GET THE PREVIOUS PATH LOOKED AT BY A DERMATOPATHOLOGIST (no a general pathologist). Kevin C. Smith MD FRCPC --------------------