|Bureau of Epidemiology|
|Bureau of Epidemiology||March 2001||Utah Department of Health|
|inside...||Human Papillomavirus (HPV)
Monthly Morbidity Summary
Approximately 100 distinct types of HPV have been identified (30 of which can be spread through sexual contact). They are numbered in order of identification. Based upon the risk for high-grade cervical intraepithelial neoplasia (CIN) or cervical cancer, HPV types may be grouped as in Table 12 .
Direct contact with HPV is required for transmission and the primary route of infection is through sexual activity. Nonsexual transmission can also occur. For example, transmission by fomites from inanimate objects has been supported, mostly in anecdotal reports. Autoinoculation from hand or anogenital lesions to the mouth, conjunctiva, or nose may also be a mode for transmitting HPV5. Mothers can transmit HPV to their infants during delivery and although rare, the virus can be passed in utero6. The period of communicability is unknown, but it is at least as long as visible lesions persist. The incubation period is approximately two to three months but may range anywhere from one to 20 months7.Clinical Manifestations
The following kinds of genital warts have been identified: 1) Classical pointed warts (condulomata acuminata) are cauliflower-like lesions; 2) Keratotic genital warts have a thickened horny surface; 3) Flat condylomata are sub clinical lesions that are difficult to detect; and the last type is 4) the smooth papular wart6.
In women, the warts occur on the outside and inside of the vagina, on the cervix (the opening to the uterus), or around the anus. In men, genital warts are less common. If present, they are seen on the tip of the penis; however, they also may be found on the shaft of the penis, on the scrotum, or around the anus. Rarely, genital warts can also develop in the mouth or throat of a person who has had oral sexual contact with an infected person. Genital warts often occur in clusters and can be very tiny or can spread into large masses on genital tissues. Left untreated, genital warts often disappear. Because there is no way to predict whether the warts will grow or disappear, it is important for those who suspect that they have genital warts to be examined and treated, if necessary.HPV warts may cause a number of problems during pregnancy. Sometimes they enlarge during pregnancy, making urination difficult. If the warts are on the vaginal wall, they can make the vagina less elastic and cause obstruction during delivery.
Infants born to women with genital warts can develop laryngeal papillomatosis (warts in the throat). Although a relatively rare occurrence, it is a potentially life-threatening condition for the child, requiring frequent laser surgery to prevent obstruction of the airways.Diagnosis
While visible anogenital lesions are present in some individuals infected with HPV, the majority of people with HPV infection in the genitalia do not have clinically observable disease. Conventional viral detection assays are not available for the diagnosis and tracking of HPV infection, including serologic assays and growth in cell culture. HPV may not be readily grown in cell culture because differentiating cells are necessary for a productive infection. Clinical observation and cytologic testing remain the most common methods for diagnosing HPV infection8. The Pap smear is the most frequently used cytologic method. However, relative to sensitivity and specificity, according to a meta-analysis of 62 published studies on Pap smear accuracy, the sensitivity of a Pap smear ranges from 11-99% and the specificity ranges from 14-97% 2. Therefore, it is important for women with abnormal Pap smears to have further examinations to detect and treat cervical problems.HPV DNA detection assays have also become a valuable research tool for detecting HPV infection, especially for asymptomatic individuals. There are a number of HPV DNA tests available including: Southern Blots, dot blots, in situ hybridization, polymerase chain reaction assay, and solution hybridization. Of these, the polymerase chain reaction (PCR) assay is the most sensitive. These tests are not routinely used in screening but can be beneficial in confirming differential diagnosis and in providing prognostic information, especially in determining HPV type8. Incidence and Prevalence
Approximately two-thirds of people who have sexual contact with a partner with genital warts will develop warts, usually within three months of contact. It is not possible to define the exact incidence and prevalence of HPV infection. Barriers include difficulty of diagnosis, HPVs non-reportable status, and the fact that most infections are subclinical and may go undetected 5. Despite these obstacles PCR-based diagnostic tests and
longitudinal studies with repeat viral testing in a number of populations have indicated that HPV infection is extremely common especially among sexually active young men and women. Current evidence suggests that 50% of sexually active adults have been infected with one or more of the HPV types. Figure 1 is estimated cases3.
HPV and Anogenital Cancer
Most genital HPV infections are benign, yet evidence exists to support a strong link between infection with certain types of HPV and some anogenital cancers, the most common of which is cervical cancer. The viral genome in the cells is usually integrated into the host chromosome in a manner that increases the production of E6 and E7, the genes linked with transforming activity. HPV types most commonly isolated from malignant genital tract lesions are those that demonstrate transforming activity in cultured cells, HPV 16 and HPV 18. In approximately 40-60% of cervical cancers HPV 16 is detected, while HPV 18 can be identified in another 10-20%9. As mentioned previously, it is estimated that 95% of all cervical cancers contain HPV DNA2. Similarly, HPV DNA has been detected in approximately 80% of patients with anal malignancies. HPV infection is not sufficient alone for malignant transformation of genital cells9.Risk Factors and Co-Factors
Some risk behaviors that have been linked to the transmission of HPV include unprotected sexual intercourse, coitus at an early age, sex with a promiscuous partner, and multiple sexual partners over ones lifetime. One particular study indicated that the risk for HPV infection nearly tripled among women with more than five sexual partners over their lifetime in comparison to women with only one sex partner10. Several recent studies support this, indicating that the likelihood of detecting HPV DNA increased with the number of sexual partners3.Co-factors that are suspected for the progression of HPV infection to malignancies include smoking, use of oral contraceptives (OC), and other sexually transmitted diseases10. Evidence supports a strong association between cigarette smoke, both active and passive, with HPV expression and CIN. Nicotine and other constituents of smoke are found at elevated levels in the cervical mucosa. Both HPV and cigarette smoke appear to have an independent and additive effect on suppressing cells that are an integral part of cell-mediated immunity. Whether cigarette smoke acts as a co-factor, an immune suppressant, or both remains unresolved2. Oral contraceptives may be a co-factor as suggested by evidence that estrogen stimulation enhances expression of the HPV 16 E6 and E7 genes in cervical carcinoma cells. The relationship of OC use to HPV infection is difficult to assess, given that OC use and sexual activity are highly correlated3. Prevention
Barrier contraceptives such as condoms are less likely to be effective in preventing infections such as genital HPV, which can involve skin not covered by a barrier contraceptive. Presently there is not sufficient data to support the efficacy of condom use for the prevention of HPV transmission. It is certain that abstinence and lifelong monogamy reduces the risk of infection since it is rare that virgins are positive for genital types of HPV DNA. Therefore condoms should be used, if only for prevention of other sexually transmitted diseases.There are reports of a potential protective effect of spermicides in the prevention of HPV and cervical cancer8. However, recent work with various papillomaviruses in animal systems indicates that the active ingredient in most spermicides, nonoxynol-9, which functions largely as a detergent that disrupts lipid envelopes, is not effective against non-enveloped viruses like papillomaviruses. The development of a prophylactic vaccine is currently in progress. The focus is upon subunit vaccines because HPV cannot be grown in tissue culture. One possible subunit vaccine is a combination of the major (L1) and minor (L2) capsid proteins of HPV. These proteins self-assemble into virus-like particles. Vaccine trials are in phase one for human trials but several prophylactic vaccines have proven to be highly effective in animals3. Treatment
Medical care focuses on treating the outcome of the HPV infection and not the infection itself. Treatment is also directed towards relieving symptoms. Destruction of the HPV lesion may not eliminate the virus, because vast areas of tissue adjacent to the lesions may be colonized. The main goal is to treat the lesions with the intention of preventing the development of neoplasias. Although, the viral load may be decreased with the elimination of the lesions5. Treatment options fall under three categories including, destructive chemicals, immune modulators, and surgical options. The following are the chemicals used in the treatment of genital warts; trichloroacetic acid (freezing), podophyllin, podofilox, and 5-flurouracil. Podophyllin and 5-fluorouracil cream should not be used during pregnancy. Immune Modulators include Alpha interferon and Imiquimod. The three surgical options are as follows, carbon dioxide laser, surgical excisions, and loop electro excision2.Conclusion
HPV usually causes a silent infection, that is one that may not have visible symptoms. Many individuals may not be aware of their infection or the potential risk of transmission to others and of developing complications. The potential seriousness of HPV infections is suggested by the apparent increase in the number of genital HPV infections being diagnosed and the fact that cervical cancer is the second leading cause of cancer deaths in women worldwide9. The possibility for developing an HPV vaccine in the future and the current progress in understanding the nature of the virus will aid in curbing this growing problem. Continued efforts of screening and treating individuals are beneficial for preventing the progression of HPV infection to malignancies.References Available Upon Request.
Quarterly Report of
Diseases of Low Frequency Year to Date, January March 2001
Department of Health, Bureau of Epidemiology
The Epidemiology Newsletter is published monthly by the Utah Department of Health, Division of Epidemiology and Laboratory Services, Bureau of Epidemiology, to disseminate epidemiologic information to the health care professional and the general public.
Send comments to: The Bureau of Epidemiology, Box 142104, Salt Lake City, UT 84114-2104, or call (801) 538-6191
Approval 8000008: Appropriation 3705
Rod Betit, Executive Director, Utah Department of Health