There are all sorts of diseases out there. Here is the culmination of my research as of February, 1999 on one of them, "HPV". -update 5-16-02- The CDC has a new STD treatment guide out. Find it at http://www.cdc.gov/std/treatment/rr5106.pdf -update 2/24/01- One more article about HPV is at the end of this doc I've quoted many sources. In the end, this research says the following: Most adults (maybe 60%) have HPV. There are at least 20 varieties of this virus. Some varieties cause tiny bumps on your privates, some big nasty bumps, some hurt, some don't. Some people have the virus and won't ever show symptoms. Usually, if you have it, any outbreaks you have will get less extreme over time, many times going away completely. Some varieties increase a woman's risk of cervical cancer between 2 and 10 times. Yes, you are probably contagious. When I say "some varieties" cause this or that, I'm sure that you want to know -which- varieties, if you have that variety, and what can you do about it. Well, the research hasn't been done that says which varieties cause which symptoms and there's nothing you can do about it anyway. There are no cures, no prevention except abstinence from all intimate contact. That leads to the only real measure anyone can take, and that's a Pap smear for women every 6 months to look for cancer. And you should be doing that anyway. If the bumps look really bad, you can go to a doctor and have them surgically removed but they'll probably come back. So, when the doctor says you have HPV, don't flip out. -------------------------------------------- http://www.thriveonline.com/health/Library/CAD/abstract26343.html Genital human papillomavirus (HPV) is a disease characterized by genital warts; if (rarely) an infant contracts the virus during delivery, the baby could develop warts in the larynx that would need to be surgically removed. http://www.thriveonline.com/health/Library/CAD/abstract27537.html A new study suggests that preventing HPV (human papilloma virus, particularly HPV-16) infection might prevent anal cancer. HPV-16 is responsible for about half of all cervical cancers. The incidence of anal cancer has increased, especially among women. A 1997 study reported in the New England Journal of Medicine showed that, of 1505 patients in Sweden and Denmark, 84% of those with anal cancer had tumors that tested positive for high-risk types of human papilloma virus (HPV), notably HPV-16. In contrast, control patients with adenocarcinoma of the rectum showed no HPV presence. Interviews revealed that anal cancer risk was related to: 1) a relatively high number of lifetime sexual partners (10+); 2) early sexual experience (<16); 3) history of anal intercourse; 4)history of venereal disease (e.g., anogenital warts); or 5) were women with promiscuous partners. Tumor samples in HPV patients and controls were measured for HPV DNA using PCR (polymerase chain reaction) analysis. Researcher K. Shaw, Johns Hopkins, Baltimore, noted that there is strong proof that HPV causes cervical cancer, and that there are additional sites (e.g., anus, vulva) where the same virus may be at work. The majority of men and women patients with anal cancer reported no history of anal intercourse. How they became infected is unknown. http://www.thriveonline.com/health/Library/CAD/abstract27999.html A three-year study at Rutgers University showed that 60% of female students were infected with the human papilloma virus. http://www.thriveonline.com/health/Library/CAD/abstract27353.html New technologies have made the early detection of cervical cancer more accurate, and almost all cervical precancers can be successfully treated. Even so, almost 5,000 women will die from the disease this year due to the growing number of women who are at risk, and the large number of women who don't take their gynological exams seriously. The more educated you are, the more likely that you won't have to worry. Cervical cancer is induced by the human papillomavirus (HPV), which is sexually transmitted. Risk factors include a high number of sexual partners, sexual intercourse before the age of 20, a history of genital HPV or other sexually transmitted diseases, other genital tract tumors or a prior cervical lesion, and using oral contraceptives for more than 5 years. Smoking, vitamin deficiencies and race may also be involved. Pap smears are important because precancerous changes generally don't have any symptoms. Experts recommend a first Pap at age 18 or when sexual activity starts, and an annual test thereafter. Pap smears aren't foolproof; there are a high percentage of false negatives. This may be due to an inadequate specimen, failure to locate the abnormality and misinterpretation of the results. Newer technologies can eliminate some of these problems. Make sure your healthcare provider uses a high-quality lab. If you develop symptoms of cervical cancer, see your physician immediately. Physicians have greatly improved the way they diagnose and treat precancers. Some experts believe that doctors are being overly cautious, resulting in unnecessary procedures, but that is more of a nuisance and expense than a danger. One encouraging area of research involves HPV testing and vaccines. http://www.thriveonline.com/health/Library/CAD/abstract26279.html In the 50 years following the introduction of the Pap smear, the death rate from cervical cancer has fallen precipitously. Pap screening has also resulted in fewer cases of cervical cancer, because it is now possible to treat pre-cancerous cervical changes. The National Cancer Institute has just launched a study to address the issue of whether mild cervical changes require treatment or can be managed with watchful waiting. Researchers plan to enroll some 7,000 women who exhibit abnormal cervical cells. It is hoped the study will determine whether watchful waiting is appropriate, possibly sparing many women the inconvenience and discomfort of colposcopy. Also, the study may reveal information about the association between human papilloma virus (HPV) and cervical cancer. http://www.thriveonline.com/health/Library/CAD/abstract25158.html Drexler M 961205 Most breast and cervical precancers don't invade surrounding tissue and don't threaten life. Most low-grade cervical precancers change back to normal cells; and precancers of the breast that are surgically removed usually do not return. However, these precancers are challenging for doctors and patients. While the treatment of precancer is highly controversial, the chances of making informed medical decisions are increasing. Most breast precancers are ductal carcinoma in situ (DCIS). DCIS is common, and usually appears as a cluster of microcalcifications on a mammogram. The lesion may remain dormant throughout a woman's life. If detected and removed, there is an 80 percent chance that the lesion will never return. About half of the recurrences become invasive cancer. Women with DCIS are closely monitored, so invasive cancers are generally found early, when they are most curable. If your doctor suspects DCIS, he will refer you to a surgeon for a biopsy. Usually, the sample is normal, and you won't need further treatment. If the sample is DCIS, seek a second opinion. There are many options should the lesion turn out to be DCIS, but none appear to have clear advantages. Doctors often disagree among themselves as to the best treatment. The size and appearance of a lesion and the edges of the biopsy tissue can sometimes indicate the likelihood of the precancer to progress and which treatment is best. Depending on the lesion's characteristics, doctors may choose no treatment, an excision of additional tissue, radiation, or a mastectomy. Treatment choices often vary, even among women with similar conditions. Cervical cancer has decreased largely because of the Pap smear, which allows doctors to detect cervical precancers and treat them early. However, cervical precancers are on the rise, possibly due to shifting sexual habits. Some doctors believe the increase reflects new medical definitions of precancer. The most common abnormality found on a Pap smear is atypical squamous cells of undetermined significance (ASCUS), which means your doctor isn't sure what's wrong or whether the cells are indeed precancerous. If you have ASCUS, you should have another Pap test in 4-6 months. Another possible finding is squamous intraepithelial lesion (SIL). SIL cells usually return to normal on their own, so treatment of low-grade SIL is very controversial. Your doctor may examine the lesion with a colposcope and do a biopsy. After the biopsy, the precancerous lesion is referred to as cervical intraepithelial neoplasia (CIN) and graded 1,2 or 3 based on its penetration of the epithelium. If you have CIN 2 or 3, your doctor will want to remove it; with CIN 1, the choice is yours. Ninety-three percent of cervical cancers contain genetic material from the human papillomavirus (HPV). Scientists think that HPV infections can change healthy cells into malignant ones. HPV typing is in the preliminary stages. http://www.thriveonline.com/health/Library/CAD/abstract24409.html The Pap smear is a fifty-one-year-old cancer-screening technique that involves scraping cells off the cervix with a tiny brush or spatula and examining them for precancerous changes. This screening has decreased cervical cancer deaths in the United States by 70 percent; when detected early, this highly curable disease approaches 95 percent positive treatment. However, there has been a ten percent increase in cervical cancer in women under 50; the suspected rise may be due to the increase in cases of the human papilloma virus, or HPV, a sexually transmitted disease that can cause genital warts and is associated with cervical cancer. Human error, 3 to 5 percent, is accountable for labeling Pap smears negative when they actually contain an abnormality. The Food and Drug Administration (FDA) has approved several new techniques for use in conjunction with the Pap smear. Speculoscopy views the cervix with a special blue-white light; abnormalities appear white. There are also two new automated systems that double-check negative smears. Labs have been regulated since 1988 by the federal Clinical Laboratory Improvements Act (CLIA). Since 1992, CLlA has mandated that cytotechnologists (the first to screen the smear) not read more than 100 slides in a 24-hour period. Many pathologists believe 50 to 60 slides a day is the maximum level of tolerance. If a pathologist is familiar with a patient's symptoms and/or previous Pap smears, a more careful inspection may be done. Women should be aware that irregular bleeding and vaginal discharge are warning signs; regular screening is recommended for women over 18. Once childbearing years are over, women should continue with yearly Pap smears. The lab reading your Pap should be certified by CLIA. Abnormal reporting rate of the lab should compare to the regional norms which are monitored by the Health Care Financing Administration. http://www.thriveonline.com/health/Library/CAD/abstract25028.html (read the Conclusion at the end) Trimble CL; Hildesheim A; Brinton LA; Shah KV; Kurman RJ (96123199 NLM) OBJECTIVE: To correlate various previously identified risk factors, different histologic types, and the presence of human papillomaviruses (HPV) in squamous vulvar carcinomas and intraepithelial precursor lesions. METHODS: Cases of squamous vulvar carcinomas and intraepithelial precursor lesions from a case-control study were analyzed by histologic type, the presence of HPV, and HPV type. These findings were correlated with demographic and interview data. RESULTS: Significant differences (P < .001) in the prevalence of HPV DNA were noted between the following: 1) patients with high-grade vulvar intraepithelial neoplasia (VIN) (48 of 54 [88.9%]), 2) different types of squamous carcinomas, designated basaloid and warty carcinomas (18 of 21 [85.7%]), and 3) keratinizing squamous carcinoma (three of 48 [6.3%]). When the risk factor profiles for basaloid or warty carcinoma and keratinizing squamous carcinoma were compared, it was found that basaloid and warty carcinoma was significantly associated with the classical cervical cancer risk factors (lifetime number of sexual partners, age at first intercourse, abnormal Papanicolaou smears, venereal warts, low socioeconomic status, and cigarette smoking) whereas keratinizing squamous carcinoma was less strongly linked to these factors and in some cases not at all. The risk profile for VIN was similar to that of basaloid and warty carcinoma (with respect to sexual and reproductive history and smoking), although effects were weaker for some factors. CONCLUSION: The results of this study further support the view that vulvar carcinoma has two different etiologies, one related to HPV infection and one that is not. http://www.thriveonline.com/health/Library/CAD/abstract23690.html Lehtinen M; et al (96177494 NLM) OBJECTIVE:To study human papillomavirus type 16 in the aetiology of cervical carcinoma. DESIGN:Within a cohort of 18814 Finnish women followed up to 23 years a nested case-control study was conducted based on serological diagnosis of past infection with human papillomavirus type 16. SUBJECTS:72 women (27 with invasive carcinoma and 45 with in situ carcinoma) and 143 matched controls were identified during the follow up. MAIN OUTCOME MEASURE:Relative risk of cervical carcinoma in presence of IgG antibodies to human papillomavirus type 16. RESULTS:After adjustment for smoking and for antibodies to various other agents of sexually transmitted disease, such as herpes simplex virus type 2 and Chlamydia trachomatis, the only significant association was with infection with human papillomavirus type 16 (odds ratio 12.5; 95% confidence interval 2.7 to 57, 2P<0.001). CONCLUSION:This prospective study provides epidemiological evidence that infection with human papillomavirus type 16 confers an excess risk for subsequent development of cervical carcinoma. http://www.thriveonline.com/health/Library/CAD/abstract9001.html Human papillomavirus infection and its relationship to recent and distant sexual partners. Obstet Gynecol 1994 Nov;84(5):755-9 Fairley CK; Chen S; Ugoni A; Tabrizi SN; Forbes A; Garland SM (95022483 NLM) OBJECTIVE: To determine the relation between the detection of genital human papillomavirus (HPV) DNA and the number of new sexual partners in the last year, 1-5 years, and 5-10 years. METHODS: In a cross-sectional study, 298 women collected tampon specimens and completed self-answer questionnaires on the known risk factors for HPV infection, including the number of sexual partners during the last 1, 5, and 10 years. The tampons were analyzed for the presence of HPV DNA by polymerase chain reaction using L1 consensus primers. RESULTS: Ninety-two (30.9%) tampons were positive for HPV DNA. In univariate analysis, the presence of HPV DNA was associated with a younger age, single marital status, a previously abnormal or currently abnormal Papanicolaou smear, and one or more new sexual partners in the last year, 1-5 years, and 5-10 years. The presence of HPV DNA was not associated with education level, past pregnancy, current or past oral contraceptive use, or the age at first intercourse. In multivariate analysis, only the number of sexual partners during the last year and 1-5 years, and a previously abnormal Papanicolaou smear were associated with HPV. CONCLUSION: The presence of HPV DNA is best predicted by the number of new sexual partners in the last 5 years. Transiently detectable HPV DNA is one possible explanation for this observation. http://www.thriveonline.com/health/Library/CAD/abstract8973.html Interval between menarche and first sexual intercourse, related to risk of human papillomavirus infection. J Pediatr 1994 Oct;125(4):661-6 Shew ML; Fortenberry JD; Miles P; Amortegui AJ (95017354 NLM) The purpose of this investigation was to study the occurrence of human papillomavirus (HPV) infection in relation to the interval between menarche and first intercourse. Two hundred eight subjects, aged 13 to 21 years, were recruited from an ambulatory adolescent clinic. Patients were excluded if they had a history of genital warts or an abnormal Papanicolaou smear. All subjects completed a self-administered questionnaire regarding demographics and their menstrual, sexual, and contraceptive histories. HPV infection was determined by in situ hybridization or changes consistent with HPV on a Papanicolaou smear, or both. The prevalence of HPV infection was 19.2%. The average interval between menarche and onset of sexual activity was 26.6 months for those who were found to have HPV infection compared with 35.7 months for those whose test results were negative (p = 0.02). First sexual intercourse within 18 months of menarche was associated with a significant elevation of risk of HPV infection, in comparison with that in adolescents who postpone first intercourse 3 to 4 years after menarche. These data suggest that factors such as increased biologic vulnerability may play a role in HPV infections among adolescent women. http://www.thriveonline.com/health/Library/CAD/abstract7567.html This study is from 1993 Variability of human papillomavirus DNA testing in a longitudinal cohort of young women. Obstet Gynecol 1993 Oct;82(4 Pt 1):578-85 Moscicki AB; Palefsky J; Smith G; Siboshski S; Schoolnik G (93390823 NLM) OBJECTIVE: To determine the variability in human papillomavirus (HPV) DNA testing of the cervix in young women found positive for HPV DNA by dot blot hybridization on routine examination. METHODS: Young women who were found to be HPV DNA-positive on routine screening using an RNA-DNA dot blot hybridization method were asked to return for repeat HPV DNA sampling, cytology, colposcopic examination, and biopsy if indicated. Those who had no histologic evidence of cervical dysplasia were asked to return every 4 months for cytology and HPV DNA testing using standardized RNA-DNA hybridization and polymerase chain reaction techniques. RESULTS: The women were followed for a mean of 27.6 months (range 13-40) with a mean of six visits (range four to ten). One-third of the women remained consistently or intermittently HPV DNA-positive by RNA-DNA dot blot hybridization, and almost 50% of the women remained consistently or intermittently positive using polymerase chain reaction techniques. Women were more likely to be positive by polymerase chain reaction than by RNA-DNA hybridization at both 1 year and after 2 years of follow-up (P < .05). However, rates for persistent positive tests by either method were similar at 1 and 2 years of follow-up. Forty percent of the subjects had new or different types than the original HPV type appear during follow-up. All five women who had evidence of spontaneous regression of cytologic abnormalities became HPV DNA-negative by both methods. CONCLUSIONS: Our data suggest that a portion of women infected with HPV appear to eliminate the infection over a relatively short period and are at low or no risk of developing disease. Persistent DNA negativity was also found in those women undergoing spontaneous regression. However, a substantial proportion of women remained intermittently positive by RNA-DNA hybridization and polymerase chain reaction. This finding suggests that the virus remains latent in some individuals and may undergo reactivation, defined by sufficient replication to allow detection by means less sensitive than polymerase chain reaction. from 1992 http://www.thriveonline.com/health/Library/CAD/abstract17605.html HPV and cancer. Self 1992 May;14(5):138-139,176 Michaels J 930872 The human papillomavirus (HPV) is a sexually transmitted disease (STD) that usually has no apparent symptoms, is a trigger for abnormal Pap test results and is linked to some precancerous conditions. Scientists have identified some 60 types of the virus, and 20 or more of these can lead to genital warts or other signs of infection in the genital tract. Confirming the infection is very difficult: one ultrasensitive test designed to detect specific forms of viral DNA indicated that 60 to 100 percent of those tested were HPV-positive. For most people, the virus is benign; the vast majority of HPV-infected women will not develop cervical cancer. The overwhelming majority of abnormal Pap test results may signal a precancerous condition of the cervix often caused by HPV infection. It is only when the condition is neglected that cancer can result. When detected early, the disease can be completely and easily cured. Two HPV- induced conditions always warrant treatment: visible genital warts that cause a burning sensation or painful intercourse and HPV-damaged cells showing precancerous changes. It is not easy to prevent the transmission of the virus, which can be spread by any genital-to-genital contact. The best insurance is to limit the number of sex partners. http://www.thriveonline.com/health/Library/CAD/abstract16821.html The pap test and beyond. Prevention 1992 Aug;44(8):59-64,126-129,132 Solimini C; McVeigh G 930088 Research suggests that there are several contributing factors for cervical cancer. Additionally, all evidence points to a primary trigger: human papillomavirus (HPV). The same group of viruses, which are usually spread through sexual contact, also causes genital warts. There are more than 20 different strains of genital HPV. For most women, the only clue that they've been exposed to a cervix-attacking virus is an abnormal Pap smear, identified as dysplasia. HPV, as well as cervical dysplasia, is extremely common, especially in very sexually active women. One theory is that certain HPV strains may be more virulent and more likely to lead to cancer. Others suspect that a women's nutritional status may make a difference in whether an HPV infection gets a grip. Recent research on this has focused on the B vitamin folate. In most cases, the process that transforms dysplasia to a fully developed cancer takes 5 to 15 years. The Pap test detects cellular changes at the precancerous stage, then the condition can be effectively treated, usually with minor surgery. In the future we may have a screening test to identify accurately those woman who've been exposed to any cancer-causing strain of HPV. Having multiple partners is considered the number-one risk factor for cervical cancer. Just as important is your partner's sexual history. Men can carry the triggering viruses without developing any symptoms that would be outwardly evident. Condoms may help prevent infection, but they're not 100 percent effective against HPV. Longtime smokers are twice as likely to get cervical cancer. Even passive exposure to cigarette smoke can increase a woman's risk. Evidence shows that antioxidants can exert a protective effect against different types of cancer. Researchers have begun to examine their possible connection to cervical cancer. Researchers found that women who remained physically active throughout their lives were 2 1/2 times less susceptible to cervical and other cancers of the reproductive system. Douching is not only unnecessary for cleanliness, it can be hazardous to you cervical health. http://www.thriveonline.com/health/Library/CAD/abstract6198.html High frequency of human papillomavirus infection in carcinoma of the urinary bladder. Cancer 1992 Oct 1;70(7):1967-73 Anwar K; Naiki H; Nakakuki K; Inuzuka M (92405087 NLM) BACKGROUND AND METHODS. The prevalence of type 6, 11, 16, 18, and 33 human papillomavirus (HPV) was investigated with the polymerase chain reaction (PCR) on formalin-fixed, paraffin wax-embedded material, including 48 neoplastic and 21 normal urinary bladder specimens. The PCR-amplified DNA were analyzed by gel electrophoresis and dot blot and Southern blot hybridization. Some tissues were tested further by nonisotopic in situ hybridization. RESULTS. HPV DNA was detected in 39 (81%) of 48 carcinomas and 7 (33%) of 21 normal urinary bladder specimens. The presence of high-risk HPV (types 16, 18, and 33) was increased significantly in carcinoma cases (62%) as compared with normal specimens (14%) (P less than 0.01). Similarly, multiple HPV infections were significantly higher in carcinoma (60%) than in the normal tissues (5%) (P less than 0.01). The overall and high-risk HPV infections in both neoplastic and normal specimens were distributed almost equally in male and female patients. There was no significant correlation between positive results for HPV and histologic grades of the carcinoma. CONCLUSIONS. These results demonstrate that the urinary bladder in both sexes is another site where infection with the common genital tract HPV may carry a risk of malignant transformation. http://www.thriveonline.com/health/Library/CAD/abstract5555.html (the sample size here is FAR too small but...) Children with condylomata acuminata. J Fam Pract 1992 Apr;34(4):419-23 Derksen DJ (92211300 NLM) BACKGROUND. The modes of transmission of genital human papillomavirus (HPV) infection in children are controversial. Studies have varied in reporting suspicion of sexual abuse in children with condylomata acuminata from zero to 90.9%. Possible modes of transmission include sexual, from mother to infant in utero, passage through an infected birth canal, infection of a nongenital type virus to the genital area, and nonsexual acquisition from a fomite. METHODS. Seven children, ranging in age from 2 to 12 years, who had genital HPV infections were assessed for sexual abuse. An interview with each child was conducted and an examination with a colposcope of the external genitalia was performed. A shave biopsy of a representative genital lesion was obtained. The tissue was sent for HPV typing. RESULTS. Six of the children had perianal warts; the seventh had a labial lesion. Five of the children (71%) had been sexually abused as determined by the history, physical examination, or an investigation by Child Protective Services. Five had HPV type 6 or 11, one had HPV type 16 or 18, and one had a novel HPV type. CONCLUSIONS. Genital types of HPV (6 or 11, 16 or 18, and others) should alert the family physician to proceed with a careful assessment for sexual abuse. This study supports the findings of other reports that genital HPV infection can be the result of sexual abuse and points out the usefulness of HPV typing. Here are some misleading numbers from http://www.3m.com/market/healthcare/pharm/aldara/pros.html Genital warts are caused by the human papilloma virus (HPV), and is the fastest growing sexually transmitted disease with 750,000 new cases each year. ... An estimated 4 million Americans suffer from genital warts. 12. What About HPV, Genital Warts And Cancer? The types of HPV linked to cervical cancer usually are not the types that cause genital warts. But a woman with genital warts, like any other sexually active woman, should get yearly Pap smears. Yearly Pap smears are the best safeguard against cervical cancer. Pap smears detect abnormal cells present on the surface of the cervix. Cancer almost always can be prevented through the early detection and treatment of abnormal cervical tissue. 14. How Can I Avoid Getting HPV Or Genital Warts? Certain ways to lower your risk of getting any sexually transmitted disease also may be effective with HPV or genital warts: You can reduce your risk of getting HPV or genital warts by not having sex with anyone or by having sex only with one uninfected partner who has sex only with you. People who have many sexual partners are at higher risk of getting sexually transmitted infections. Latex condoms ("rubbers"), used properly from start to finish each time you have sex, provide some protection if they cover the area of the HPV infection. Condoms are recommended with all new or casual sexual partners. Spermicidal foams, creams, and jellies are not proven to act against HPV and genital warts, but they are effective against some other STDs. They are best used along with condoms, not in place of condoms. This is from the CDC's 1998 report: 1998 Guidelines for Treatment of Sexually Transmitted Diseases http://www.cdc.gov/epo/mmwr/preview/mmwrhtml/00050909.htm Two highlights ...in the absence of curative therapy, treatment to reduce transmission is not realistic.... ...Examination of sex partners is unnecessary. Most sex partners of infected patients probably are already infected subclinically with HPV. No practical screening tests for subclinical infection are available. The use of condoms may reduce transmission to sex partners who are likely to be uninfected (e.g., new partners); however, the period of communicability is unknown. Whether patients who have subclinical HPV infection are as contagious as patients who have exophytic warts is unknown.... The article implies that HPV is amazingly prevelant. You can't stop from getting it but it really isn't very bad. The worst part might be unsightly warts or slight pain during an outbreak. But the outbreaks get progressively less intense as you have the disease. They don't talk about a direct relationship between it and cervical cancer but do talk about how having any STD increases the likelihood of cervical cancer. --------------------------------------------------- ... HUMAN PAPILLOMAVIRUS INFECTION Genital Warts More than 20 types of HPV can infect the genital tract. Most HPV infections are asymptomatic, subclinical, or unrecognized. Visible genital warts usually are caused by HPV types 6 or 11. Other HPV types in the anogenital region (i.e., types 16, 18, 31, 33, and 35) have been strongly associated with cervical dysplasia. Diagnosis of genital warts can be confirmed by biopsy, although biopsy is rarely needed (e.g., if the diagnosis is uncertain; the lesions do not respond to standard therapy; the disease worsens during therapy; the patient is immunocompromised; or warts are pigmented, indurated, fixed, and ulcerated). No data support the use of type-specific HPV nucleic acid tests in the routine diagnosis or management of visible genital warts. HPV types 6 and 11 also can cause warts on the uterine cervix and in the vagina, urethra, and anus; these warts are sometimes symptomatic. Intra-anal warts are seen predominately in patients who have had receptive anal intercourse; these warts are distinct from perianal warts, which can occur in men and women who do not have a history of anal sex. Other than the genital area, these HPV types have been associated with conjunctival, nasal, oral, and laryngeal warts. HPV types 6 and 11 are associated rarely with invasive squamous cell carcinoma of the external genitalia. Depending on the size and anatomic locations, genital warts can be painful, friable, and/or pruritic. HPV types 16, 18, 31, 33, and 35 are found occasionally in visible genital warts and have been associated with external genital (i.e., vulvar, penile, and anal) squamous intraepithelial neoplasia (i.e., squamous cell carcinoma in situ, bowen-oid papulosis, Erythroplasia of Queyrat, or Bowen's disease of the genitalia). These HPV types have been associated with vaginal, anal, and cervical intraepithelial dysplasia and squamous cell carcinoma. Patients who have visible genital warts can be infected simultaneously with multiple HPV types. Treatment The primary goal of treating visible genital warts is the removal of symptomatic warts. Treatment can induce wart-free periods in most patients. Genital warts often are asymptomatic. No evidence indicates that currently available treatments eradicate or affect the natural history of HPV infection. The removal of warts may or may not decrease infectivity. If left untreated, visible genital warts may resolve on their own, remain unchanged, or increase in size or number. No evidence indicates that treatment of visible warts affects the development of cervical cancer. Regimens Treatment of genital warts should be guided by the preference of the patient, the available resources, and the experience of the health-care provider. None of the available treatments is superior to other treatments, and no single treatment is ideal for all patients or all warts. The available treatments for visible genital warts are patient-applied therapies (i.e., podofilox and imiquimod) and provider-administered therapies (i.e., cryotherapy, podophyllin resin, trichloroacetic acid {TCA}, bichloroacetic acid {BCA}, interferon, and surgery). Most patients have from one to 10 genital warts, with a total wart area of 0.5-1.0 cm2, that are responsive to most treatment modalities. Factors that might influence selection of treatment include wart size, wart number, ana-tomic site of wart, wart morphology, patient preference, cost of treatment, convenience, adverse effects, and provider experience. Having a treatment plan or protocol is important, because many patients will require a course of therapy rather than a single treatment. In general, warts located on moist surfaces and/or in intertriginous areas respond better to topical treatment (e.g., TCA, podophyllin, podofilox, and imiquimod) than do warts on drier surfaces. The treatment modality should be changed if a patient has not improved substantially after three provider-administered treatments or if warts have not completely cleared after six treatments. The risk-benefit ratio of treatment should be evaluated throughout the course of therapy to avoid overtreatment. Providers should be knowledgeable about, and have available to them, at least one patient-applied and one provider-administered treatment. Complications rarely occur if treatments for warts are employed properly. Patients should be warned that scarring in the form of persistent hypopigmentation or hyperpigmentation is common with ablative modalities. Depressed or hypertrophic scars are rare but can occur, especially if the patient has had insufficient time to heal between treatments. Treatment can result rarely in disabling chronic pain syndromes (e.g., vulvodynia or hyperesthesia of the treatment site). External Genital Warts, Recommended Treatments Patient-Applied: Podofilox 0.5% solution or gel. Patients may apply podofilox solution with a cotton swab, or podofilox gel with a finger, to visible genital warts twice a day for 3 days, followed by 4 days of no therapy. This cycle may be repeated as necessary for a total of four cycles. The total wart area treated should not exceed 10 cm2, and a total volume of podofilox should not exceed 0.5 mL per day. If possible, the health-care provider should apply the initial treatment to demonstrate the proper application technique and identify which warts should be treated. The safety of podofilox during pregnancy has not been established. OR Imiquimod 5% cream. Patients should apply imiquimod cream with a finger at bedtime, three times a week for as long as 16 weeks. The treatment area should be washed with mild soap and water 6-10 hours after the application. Many patients may be clear of warts by 8-10 weeks or sooner. The safety of imiquimod during pregnancy has not been established. Provider-Administered: Cryotherapy with liquid nitrogen or cryoprobe. Repeat applications every 1 to 2 weeks. OR Podophyllin resin 10%-25% in compound tincture of benzoin. A small amount should be applied to each wart and allowed to air dry. To avoid the possibility of complications associated with systemic absorption and toxicity, some experts recommend that application be limited to less than or equal to 0.5 mL of podophyllin or less than or equal to 10 cm2 of warts per session. Some experts suggest that the preparation should be thoroughly washed off 1-4 hours after application to reduce local irritation. Repeat weekly if necessary. The safety of podophyllin during pregnancy has not been established. OR TCA or BCA 80%-90%. Apply a small amount only to warts and allow to dry, at which time a white "frosting" develops; powder with talc or sodium bicarbonate (i.e., baking soda) to remove unreacted acid if an excess amount is applied. Repeat weekly if necessary. OR Surgical removal either by tangential scissor excision, tangential shave excision, curettage, or electrosurgery. External Genital Warts, Alternative Treatments Intralesional interferon, OR Laser surgery. For patient-applied treatments, patients must be able to identify and reach warts to be treated. Podofilox 0.5% solution or gel is relatively inexpensive, easy to use, safe, and self-applied by patients. Podofilox is an antimitotic drug that results in destruction of warts. Most patients experience mild/moderate pain or local irritation after treatment. Imiquimod is a topically active immune enhancer that stimulates production of interferon and other cytokines. Before wart resolution, local inflammatory reactions are common; these reactions usually are mild to moderate. Cryotherapy, which requires the use of basic equipment, destroys warts by thermal-induced cytolysis. Its major drawback is that proper use requires substantial training, without which warts are frequently overtreated or undertreated, resulting in poor efficacy or increased likelihood of complications. Pain after application of the liquid nitrogen, followed by necrosis and sometimes blistering, are not unusual. Although local anesthesia (topical or injected) is not used routinely, its use facilitates treatment if there are many warts or if the area of warts is large. Podophyllin resin contains a number of compounds, including the podophyllin lignans that are antimitotic. The resin is most frequently compounded at 10%-25% in tincture of benzoin. However, podophyllin resin preparations differ in the concentration of active components and contaminants. The shelf life and stability of podophyllin preparations are unknown. It is important to apply a thin layer of podophyllin resin to the warts and allow it to air dry before the treated area comes into contact with clothing. Overapplication or failure to air dry can result in local irritation caused by spread of the compound to adjacent areas. Both TCA and BCA are caustic agents that destroy warts by chemical coagulation of the proteins. Although these preparations are widely used, they have not been investigated thoroughly. TCA solutions have a low viscosity comparable to water and can spread rapidly if applied excessively, thus damaging adjacent normal tissue. Both TCA and BCA should be applied sparingly and allowed to dry before the patient sits or stands. If pain is intense, the acid can be neutralized with soap or sodium bicarbonate (i.e., baking soda). Surgical removal of warts has an advantage over other treatment modalities in that it renders the patient wart-free, usually with a single visit. However, substantial clinical training, additional equipment, and a longer office visit are required. Once local anesthesia is achieved, the visible genital warts can be physically destroyed by electrosurgery, in which case no additional hemostasis is required. Alternatively, the warts can be removed either by tangential excision with a pair of fine scissors or a scalpel or by curettage. Because most warts are exophytic, this can be accomplished with a resulting wound that only extends into the upper dermis. Hemostasis can be achieved with an electrosurgical unit or a chemical styptic (e.g., an aluminum chloride solution). Suturing is neither required nor indicated in most cases when surgical removal is done properly. Surgery is most beneficial for patients who have a large number or area of genital warts. Carbon dioxide laser and surgery may be useful in the management of extensive warts or intraurethral warts, particularly for those patients who have not responded to other treatments. Interferons, either natural or recombinant, used for the treatment of genital warts have been administered systemically (i.e., subcutaneously at a distant site or IM) and intralesionally (i.e., injected into the warts). Systemic interferon is not effective. The efficacy and recurrence rates of intralesional interferon are comparable to other treatment modalities. Interferon is believed to be effective because of antiviral and/or immunostimulating effects. However, interferon therapy is not recommended for routine use because of inconvenient routes of administration, frequent office visits, and the association between its use and a high frequency of systemic adverse effects. Because of the shortcomings of available treatments, some clinics employ combination therapy (i.e., the simultaneous use of two or more modalities on the same wart at the same time). Most experts believe that combining modalities does not increase efficacy but may increase complications. Cervical Warts For women who have exophytic cervical warts, high-grade squamous intraepithelial lesions (SIL) must be excluded before treatment is begun. Management of exophytic cervical warts should include consultation with an expert. Vaginal Warts Cryotherapy with liquid nitrogen. The use of a cryoprobe in the vagina is not recommended because of the risk for vaginal perforation and fistula formation. OR TCA or BCA 80%-90% applied only to warts. Apply a small amount only to warts and allow to dry, at which time a white "frosting" develops; powder with talc or sodium bicarbonate (i.e., baking soda) to remove unreacted acid if an excess amount is applied. Repeat weekly if necessary. OR Podophyllin 10%-25% in compound tincture of benzoin applied to a treated area that must be dry before the speculum is removed. Treat with less than or equal to 2 cm2 per session. Repeat application at weekly intervals. Because of concern about potential systemic absorption, some experts caution against vaginal application of podophyllin. The safety of podophyllin during pregnancy has not been established. Urethral Meatus Warts Cryotherapy with liquid nitrogen, OR Podophyllin 10%-25% in compound tincture of benzoin. The treatment area must be dry before contact with normal mucosa. Podophyllin must be applied weekly if necessary. The safety of podophyllin during pregnancy has not been established. Anal Warts Cryotherapy with liquid nitrogen. OR TCA or BCA 80%-90% applied to warts. Apply a small amount only to warts and allow to dry, at which time a white "frosting" develops; powder with talc or sodium bicarbonate (i.e., baking soda) to remove unreacted acid if an excess amount is applied. Repeat weekly if necessary. OR Surgical removal. Note: Management of warts on rectal mucosa should be referred to an expert. Oral Warts Cryotherapy with liquid nitrogen, OR Surgical removal. Follow-Up After visible genital warts have cleared, a follow-up evaluation is not mandatory. Patients should be cautioned to watch for recurrences, which occur most frequently during the first 3 months. Because the sensitivity and specificity of self-diagnosis of genital warts is unknown, patients concerned about recurrences should be offered a follow-up evaluation 3 months after treatment. Earlier follow-up visits also may be useful a) to document a wart-free state, b) to monitor for or treat complications of therapy, and c) to provide the opportunity for patient education and counseling. Women should be counseled regarding the need for regular cytologic screening as recommended for women without genital warts. The presence of genital warts is not an indication for cervical colposcopy. Management of Sex Partners Examination of sex partners is not necessary for the management of genital warts because the role of reinfection is probably minimal and, in the absence of curative therapy, treatment to reduce transmission is not realistic. However, because self- or partner-examination has not been evaluated as a diagnostic method for genital warts, sex partners of patients who have genital warts may benefit from examination to assess the presence of genital warts and other STDs. Sex partners also might benefit from counseling about the implications of having a partner who has genital warts. Because treatment of genital warts probably does not eliminate the HPV infection, patients and sex partners should be cautioned that the patient might remain infectious even though the warts are gone. The use of condoms may reduce, but does not eliminate, the risk for transmission to uninfected partners. Female sex partners of patients who have genital warts should be reminded that cytologic screening for cervical cancer is recommended for all sexually active women. Special Considerations Pregnancy Imiquimod, podophyllin, and podofilox should not be used during pregnancy. Because genital warts can proliferate and become friable during pregnancy, many experts advocate their removal during pregnancy. HPV types 6 and 11 can cause laryngeal papillomatosis in infants and children. The route of transmission (i.e., transplacental, perinatal, or postnatal) is not completely understood. The preventive value of cesarean section is unknown; thus, cesarean delivery should not be performed solely to prevent transmission of HPV infection to the newborn. In rare instances, cesarean delivery may be indicated for women with genital warts if the pelvic outlet is obstructed or if vaginal delivery would result in excessive bleeding. Immunosuppressed Patients Persons who are immunosuppressed because of HIV or other reasons may not respond as well as immunocompetent persons to therapy for genital warts, and they may have more frequent recurrences after treatment. Squamous cell carcinomas arising in or resembling genital warts might occur more frequently among immunosuppressed persons, requiring more frequent biopsy for confirmation of diagnosis. Squamous Cell Carcinoma in situ Patients in whom squamous cell carcinoma in situ of the genitalia is diagnosed should be referred to an expert for treatment. Ablative modalities usually are effective, but careful follow-up is important. The risk for these lesions leading to invasive squamous cell carcinoma of the external genitalia in immunocompetent patients is unknown but is probably low. Female partners of patients who have squamous cell carcinoma in situ are at high risk for cervical abnormalities. Subclinical Genital HPV Infection (Without Exophytic Warts) Subclinical genital HPV infection occurs more frequently than visible genital warts among both men and women. Infection often is indirectly diagnosed on the cervix by Pap smear, colposcopy, or biopsy and on the penis, vulva, and other genital skin by the appearance of white areas after application of acetic acid. However, the routine use of acetic acid soaks and examination with light and magnification, as a screening test, to detect "subclinical" or "acetowhite" genital warts is not recommended. Acetowhitening is not a specific test for HPV infection. Thus, in populations at low risk for this infection, many false-positives may be detected when this test is used for screening. The specificity and sensitivity of this procedure has not been defined. In special situations, experienced clinicians find this test useful for identification of flat genital warts. A definitive diagnosis of HPV infection depends on detection of viral nucleic acid (DNA or RNA) or capsid protein. Pap smear diagnosis of HPV does not always correlate with detection of HPV DNA in cervical cells. Cell changes attributed to HPV in the cervix are similar to those of mild dysplasia and often regress spontaneously without treatment. Tests that detect several types of HPV DNA or RNA in cells scraped from the cervix are available, but the clinical utility of these tests for managing patients is unclear. Management decisions should not be made on the basis of HPV tests. Screening for subclinical genital HPV infection using DNA or RNA tests or acetic acid is not recommended. Treatment In the absence of coexistent dysplasia, treatment is not recommended for subclinical genital HPV infection diagnosed by Pap smear, colposcopy, biopsy, acetic acid soaking of genital skin or mucous membranes, or the detection of HPV (DNA or RNA). The diagnosis of subclinical genital HPV infection is often questionable, and no therapy has been identified to eradicate infection. HPV has been demonstrated in adjacent tissue after laser treatment of HPV-associated dysplasia and after attempts to eliminate subclinical HPV by extensive laser vaporization of the anogenital area. In the presence of coexistent dysplasia, management should be based on the grade of dysplasia. Management of Sex Partners Examination of sex partners is unnecessary. Most sex partners of infected patients probably are already infected subclinically with HPV. No practical screening tests for subclinical infection are available. The use of condoms may reduce transmission to sex partners who are likely to be uninfected (e.g., new partners); however, the period of communicability is unknown. Whether patients who have subclinical HPV infection are as contagious as patients who have exophytic warts is unknown. CERVICAL CANCER SCREENING FOR WOMEN WHO ATTEND STD CLINICS OR HAVE A HISTORY OF STDs Women who have a history of STD are at increased risk for cervical cancer, and women attending STD clinics may have other risk factors that place them at even greater risk. Prevalence studies have determined that precursor lesions for cervical cancer occur about five times more frequently among women attending STD clinics than among women attending family planning clinics. The Pap smear (i.e., cervical smear) is an effective and relatively low-cost screening test for invasive cervical cancer and SIL, * the precursors of cervical cancer. Both ACOG and the American Cancer Society (ACS) recommend annual Pap smears for all sexually active women. Although these guidelines take the position that Pap smears can be obtained less frequently in some situations, women with a history of STDs may need more frequent screening because of their increased risk for cervical cancer. Moreover, surveys of women attending STD clinics indicate that many women do not understand the purpose or importance of Pap smears, and almost half of the women who have had a pelvic examination erroneously believe they have had a Pap smear when they actually have not. -------------------- The 1988 Bethesda System for Reporting Cervical/Vaginal Cytologic Diagnoses introduced the terms "low-grade SIL" and "high-grade SIL" (27). Low-grade SIL encompasses cellular changes associated with HPV and mild dysplasia/cervical intraepithelial neoplasia 1 (CIN 1). High-grade SIL includes moderate dysplasia/CIN 2, severe dysplasia/CIN 3, and carcinoma in situ/CIN 3. Recommendations At the time of a pelvic examination for STD screening, the health-care provider should inquire about the result of the patient's last Pap smear and discuss the following information with the patient: The purpose and importance of a Pap smear; Whether a Pap smear was obtained during the clinic visit; The need for an annual Pap smear; and The names of local providers or referral clinics that can obtain Pap smears and adequately follow up results (i.e., if a Pap smear was not obtained during this examination). If a woman has not had a Pap smear during the previous 12 months, a Pap smear should be obtained as part of the routine pelvic examination. Health-care providers should be aware that, after a pelvic examination, many women believe they have had a Pap smear when they actually have not, and thus may report having had a recent Pap smear. Therefore, in STD clinics, a Pap smear should be strongly considered during the routine clinical evaluation of women who have not had a normal Pap smear within the preceding 12 months that is documented within the clinic record or linked-system record. A woman may benefit from receiving printed information about Pap smears and a report containing a statement that a Pap smear was obtained during her clinic visit. If possible, a copy of the Pap smear result should be provided to the patient for her records. Follow-Up Clinics and health-care providers who provide Pap smear screening services are encouraged to use cytopathology laboratories that report results using the Bethesda System of classification. If the results of the Pap smear are abnormal, care should be provided according to the Interim Guidelines for Management of Abnormal Cervical Cytology published by the National Cancer Institute Consensus Panel and briefly summarized below (27). Aned significance (ASCUS), follow-up without colposcopy may be acceptable in circumstances when the diagnosis is not qualified further or the cytopathologist favors a reactive process. In general, this would involve repeated Pap smears every 4-6 months for 2 years until the results of three consecutive smears have been negative. If repeated smears show persistent abnormalities, colposcopy and directed biopsy are indicated for low-grade SIL and should be considered for ASCUS. Women with a diagnosis of unqualified ASCUS associated with severe inflammation should at least be reevaluated with a repeat Pap smear after 2-3 months, then repeated Pap smears every 4-6 months for 2 years until the results of three consecutive smears have been negative. If specific infections are identified, the patient should be reevaluated after appropriate treatment for those infections. In all follow-up strategies using repeated Pap smears, the tests not only must be negative but also must be interpreted by the laboratory as "satisfactory for evaluation." Because many public health clinics, including most STD clinics, cannot provide clinical follow-up of abnormal Pap smears with colposcopy and biopsy, women with Pap smears demonstrating high grade SIL or persistent low-grade SIL or ASCUS usually will need a referral to other local health-care providers or clinics for colposcopy and biopsy. Clinics and health-care providers who offer Pap smear screening services but cannot provide appropriate colposcopic follow-up of abnormal Pap smears should arrange referral services that a) can promptly evaluate and treat patients and bbe clearly documented in the clinic record. The development of colposcopy and biopsy services in local health departments, especially in circumstances where referrals are difficult and follow-up is unlikely, should be considered. Other Management Considerations Other considerations in performing Pap smears are as follows: The Pap smear is not an effective screening test for STDs. If a woman is menstruating, a Pap smear should be postponed, and the woman should be advised to have a Pap smear at the earliest opportunity. The presence of a mucopurulent discharge might compromise interpretation of the Pap smear. However, if the woman is unlikely toting or when other cultures or specimens are collected for STD diagnoses, the Pap smear may be obtained last. Women who have had a hysterectomy do not require an annual Pap smear unless the hysterectomy was related to cervical cancer or its precursor lesions. In this situation, women should be advised to continue follow-up with the physician(s) who provided health care at the time of the hysterectomy. Both health-care providers who receive basic retraining on Pap smear collection and clinics that use simple quality assurance measures obtain fewer unsatisfactory smears. Although type-specific HPV testing to identify women at high and low risk for cervical cancer may become clinically relevant in the future, its utility in clinical practice is unclear, and such testing is not recommended. Special Considerations Pregnancy Women who are pregnant should have a Pap smear as part of routine prenatal care. A cytobrush may be used for obtaining Pap smears in pregnant women, although care should be taken not to disrupt the mucous plug. -------------------------------------------- http://www.mskcc.org/medical_professionals/research/feature_virus_linked_to_pediatric_eye_tumor_body.html Last Updated : 1/24/2001 Feature: Virus Linked to Pediatric Eye Tumor Center researchers have linked the virus that causes cervical cancer to retinoblastoma, an eye tumor that is one of the most common childhood cancers. But it is the first study showing a connection between human papilloma virus (HPV) and the tumor retinoblastoma, and much more research needs to be done to firmly establish a cause-and-effect relationship. "This discovery may not change the world on a scientific level, but it has the potential to change the lives of many children and hopefully protect them from this disease," said Carlos Cordon-Cardo, Director of MSK's Division of Molecular Pathology and lead author of the study, which was recently published in Clinical Cancer Research. Retinoblastoma was the first cancer found to have a hereditary component. Scientists isolated the Rb gene, which leads to retinoblastoma when it is mutated, in the late 1980s. (The gene has since been implicated in many other types of cancer.) Retinoblastoma is often treated by removing one or both eyes and can be fatal if left untreated. Although the genetic form of the disease is well understood, until now little was known about what causes the non-familial form. Several Mexican researchers who had worked in Dr. Cordon-Cardo's lab - and had since returned to Mexico - observed that in certain inner-city hospitals in Mexico City, the incidence of retinoblastoma in young children was much higher than normal. In addition, young women in those areas had a high incidence of HPV infection, a sexually transmitted disease. The researchers decided to test for a link between these two observations. They suspected that children were being exposed to HPV during childbirth and that this virus triggered the development of retinoblastoma. Dr. Cordon-Cardo's lab obtained samples of retinoblastoma tumor tissue from 39 children who had the non-familial form of the disease. They tested the cells and found that 36 percent of tumors carried HPV 16 or HPV 18, two strains already known to cause cervical cancer. In addition, those tissues that carried the virus had a normal Rb gene. HPV makes two proteins, called E6 and E7, that can lead to cancer by turning off tumor-suppressor proteins. Tumor-suppressor proteins prevent cancer from developing, and when they are turned off cells can multiply out of control. In the case of HPV, E6 and E7 bind to the p53 and pRb tumor-suppressor proteins, respectively, blocking their tumor-suppressor activity. "It's a provocative finding," said Ira Dunkel, an MSKCC pediatric oncologist and expert in retinoblastoma. "It has great potential importance, but much more research needs to be done." According to Dr. Cordon-Cardo, researchers in developing countries throughout the world already have begun testing their retinoblastoma patients for HPV infection and are confirming the connection he found. But it remains to be seen whether the same relationship will be found in industrialized countries, where HPV infections are much less common. Once HPV is more firmly established as a cause of retinoblastoma, it is possible the disease can be prevented by encouraging women to use barrier methods of contraception that reduce HPV infection and by delivering babies of infected mothers by Caesarean section to prevent spread of the virus.