Issues in the management of human papillomavirus genital disease

Human papillomavirus (HPV) infects epithelial cells at a variety of anatomic sites. Of the more than 80 types of this virus, approximately one third infect genital tissue. Genital infection can be clinical (warts), subclinical (abnormal Papanicolaou [Pap] smears or lesions visible only with magnification and application of acetic acid) or latent (infection with apparently normal tissue). Recent research has revealed a clear association between genital warts and HPV types 6 and 11, and between cervical cancer and HPV types 16, 18 and others. Women with genital warts who have normal Pap smears do not need colposcopy. All available therapies are suboptimal because HPV is not eradicated by treatment. However, the active disease expression can be eliminated by treatment. The approach to treatment will depend on each patient's personal characteristics and preferences.     

Immunotherapy for non-Hodgkin''s lymphoma

The genital human papillomavirus (HPV) is directly associated with cervical cancer, the second most common form of cancer among women. The study was guided by a synergistic interaction model of HPV risk factors. The relative risk of selected risk factors and cofactors associated with genital HPV infections was identified. Women at highest risk for acquiring an HPV infection had (a) initiated sex before age 15, (b) more than four lifetime sex partners, (c) more than one "once only" sexual partner, and (d) chosen male sex partners who previously had > 16 other female sex partners. Cofactors that increased risk by possibly contributing to progression of genital HPV infection were initiating oral contraceptive use before age 15 and having acquired more than three other sexually transmitted diseases. Past and current smokers were at a slightly higher risk compared to nonsmokers. Although other studies have identified risk factors, few have identified the relative risk of these factors.     

Increased dose-rate effect in V79-multicellular aggregates (spheroids). Relation to initial DNA lesions and repair

We studied the papillomaviruses (HPV) found in 131 common warts from 111 immunocompetent patients by amplification of viral DNA sequences with the general-primer-mediated polymerase chain reaction (PCR). The virus types were determined by restriction-enzyme cleavage and reverse-blot analysis. Results were confirmed by using the Southern blot technique. Forty patients harboured HPV 2a, 25 individuals showed HPV 2c and 13 yielded HPV 57. Common warts from 16 patients were induced by a variant of HPV 57. HPV 7 was found in four patients. HPV 1 was identified in two patients, and there was evidence for HPV 4 in only one case. One individual yielded an HPV type which was only weakly related to HPV 2. Three patients were infected by more than one HPV type. PCR did not demonstrate HPV-DNA in warts from six individuals. The distribution and variation of HPV types found in the common warts of immunocompetent patients were similar to the findings in immunocompromised patients reported by other authors.     

Factors associated with appropriate physician management of sexually transmitted diseases in an urban Canadian center

BACKGROUND AND OBJECTIVES: To explore physicians' management of selected sexually transmitted diseases (STDs), because previous studies suggest that physicians' management practices could be improved. GOALS: To determine the estimated annual incidence of STD seen by family/general practitioners (FPs), gynecologists (GYNs) and urologists (UROLs), adequacy of STD management practices, and any associations with demographic and other characteristics. STUDY DESIGN: A self-administered questionnaire was mailed to GYNs, UROLs, and a random sample of FPs in Hamilton, Ontario. RESULTS: Eighty-one of 102 (79.4%) FPs, 27 of 32 (84.4%) GYNs, and 7 of 8 (87.5%) UROLs responded. Vaginitis, male urethritis, and genital warts in women were the most frequently observed STDs. The treatment of bacterial vaginosis and pelvic inflammatory disease were most frequently at variance with published guidelines. CONCLUSIONS: Deficiencies exist in physicians' management of both common and potentially serious STD problems.     

Sexually transmitted disease acquisition among women infected with human immunodeficiency virus type 1

Recent evidence suggests that sexually transmitted diseases (STDs) enhance the transmission of human immunodeficiency virus (HIV) type 1. In 143 HIV-infected women enrolled in a university-based longitudinal HIV clinic over 16 months (mean), the STD point prevalence was examined at enrollment and the cumulative prevalence was calculated at follow-up. At enrollment, 35 women (25%) had > or = 1 STD. These included trichomoniasis in 16 women (11%); syphilis, 9 (6%); genital herpes, 8 (6%); gonorrhea, 5 (4%); chlamydia, 5 (4%); genital warts, 2 (1%); and pelvic inflammatory disease (PID), 1 (1%). STDs were found in 55 (42%) of the 125 patients who returned for at least one follow-up visit: trichomoniasis in 23 (18%); genital herpes, 20 (12%); gonorrhea, 9 (7%); syphilis, 7 (6%); genital warts, 7 (6%); chlamydia, 5 (4%); and PID, 4 (3%). Despite counseling at both enrollment and follow-up, these women had a very high cumulative prevalence of STDs, indicating persistent high-risk sexual behavior.     

Variables and designs in psychiatric/mental health nursing research articles published from 1982 to 1992

Anogenital (AG) warts in 31 prepubertal children were HPV typed by nonisotopic in situ hybridization (NISH) using digoxigenin-labeled probes for human papilloma virus (HPV) types 1-5, 6, 11, 16, 18, 31, and 33. Mode of transmission was determined from historical, clinical, and laboratory data independent of HPV typing. HPV 2 was detected most commonly (13/31 warts) followed by HPV 6 (7/31), HPV 11 (5/31), and HPV 16 (1/31). Although not reaching statistical significance, our results suggested that a mucosal HPV type (6, 11, 16) in a child's AG warts implied transmission from mucosal warts and conversely cutaneous HPV 2 transmission from warts at a cutaneous site. HPV typing provided no helpful information regarding actual mode of transmission of AG warts in these children. The high prevalence of HPV 2 in children's AG warts and the low prevalence of sexual abuse (2 of 31 children) found in this study suggest innocent auto- or heteroinoculation from cutaneous warts may be a common means by which children acquire AG warts.     

Expression of Ets-1 transcription factor in relation to angiogenesis in the healing process of gastric ulcer

Psoralen and UVA (PUVA) photochemotherapy is associated with a dose-dependent increased risk of nonmelanoma skin cancer in patients treated for psoriasis. Like ultraviolet B radiation, PUVA is both mutagenic and immunosuppressive and may thus act as a complete carcinogen; however, the reversed squamous to basal cell carcinoma ratio (SCC:BCC) in PUVA-treated patients, also seen in immunosuppressed renal transplant recipients, suggests a possible cofactor role for human papillomavirus (HPV) infection. In this study we examine a large series of benign and malignant cutaneous lesions for the presence of HPV DNA from patients treated with high dose (> or =500 J per cm2) ultraviolet A. A panel of degenerate primers based on the L1 (major capsid protein) open reading frame was employed, designed to detect mucosal, cutaneous, and epidermodysplasia verruciformis HPV types with high sensitivity and specificity. HPV DNA was detected in 15 of 20 (75%) non-melanoma skin cancer, seven of 17 (41.2%) dysplastic PUVA keratoses, four of five (80%) skin warts, and four of 12 (33%) PUVA-exposed normal skin samples. The majority of HPV positive lesions contained epidermodysplasia verruciformis-related HPV including HPV-5, -20, -21, -23, -24, and -38. Possible novel epidermodysplasia verruciformis types were identified in further lesions. Mixed infection with epidermodysplasia verruciformis, cutaneous, and/or mucosal types was present in six of 30 (20%) of all HPV positive lesions, including in normal skin, warts, dysplastic PUVA keratoses, and squamous cell carcinomas. The prevalence and type of HPV infection in cutaneous lesions from PUVA-treated patients is similar to that previously reported in renal transplant-associated skin lesions, and suggests that the role of HPV in PUVA-associated carcinogenesis merits further study.     

Oral cancer risk in relation to sexual history and evidence of human papillomavirus infection

BACKGROUND: Experimental models and analyses of human tumors suggest that oncogenic, sexually transmittable human papillomaviruses (HPVs) are etiologic factors in the development of oral squamous cell carcinoma (SCC). We conducted a population-based, case-control study to determine whether the risk of this cancer is related to HPV infection and sexual history factors. METHODS: Case subjects (n = 284) were 18-65-year-old residents of three counties in western Washington State who were newly diagnosed with oral SCC from 1990 through 1995. Control subjects (n = 477) similar in age and sex were selected from the general population. Serum samples were tested for HPV type 16 capsid antibodies. Exfoliated oral tissue collected from case and control subjects and tumor tissue from case subjects were tested for HPV DNA. Odds ratios (ORs) were calculated after adjusting for age, sex, cigarette smoking, and alcohol consumption. RESULTS: Among males only, oral SCC risk increased with self-reported decreasing age at first intercourse, increasing number of sex partners, and a history of genital warts. Approximately 26% of the tumors in case subjects contained HPV DNA; 16.5% of the tumors contained HPV type 16 DNA. The prevalence of oncogenic HPV types in exfoliated oral tissue was similar in case and control subjects. The ORs for HPV type 16 capsid seropositivity were 2.3 (95% confidence interval [CI] = 1.6-3.3) for all oral SCCs and 6.8 (95% CI = 3.0-15.2) for oral SCCs containing HPV type 16 DNA. The joint association of cigarette smoking and HPV type 16 capsid seropositivity with oral SCC (OR = 8.5; 95% CI = 5.1-14.4) was stronger than predicted from the sum of individual associations with current smoking (OR = 3.2; 95% CI = 2.0-5.2) and seropositivity (OR = 1.7; 95% CI = 1.1-2.6). CONCLUSIONS: HPV type 16 infection may contribute to the development of a small proportion of oral SCCs in this population, most likely in combination with cigarette smoking.     

Spread of HIV infection in married monogamous women in India

CONTEXT: A high prevalence of human immunodeficiency virus (HIV) infection in female sex workers (FSWs) and men who attend sexually transmitted disease (STD) clinics poses a risk for spread of infection to other populations. OBJECTIVE: To examine spread of HIV to a low-risk population by comparing prevalence of, and risk factors for, HIV and STDs in FSWs and non-FSWs. METHODS: Women attending STD clinics in Pune, India, were assessed for STDs and HIV from May 13, 1993, to July 11, 1996. Demographic and behavioral information was collected, and clinical and laboratory assessment was performed. MAIN OUTCOME MEASURE: Prevalence and risk determinants of HIV infection. RESULTS: Of 916 women enrolled, 525 were FSWs and 391 were non-FSWs. Prevalence of HIV in FSWs and non-FSWs was 49.9% and 13.6%, respectively (P<.001). In multivariate analysis, inconsistent condom use and genital ulcer disease or genital warts were associated with prevalent HIV in FSWs. History of sexual contact with a partner with an STD was associated with HIV in non-FSWs. CONCLUSIONS: Infection with HIV is increasing in non-FSWs, previously thought to be at low risk in India. Since history of sexual contact with their only sex partner was the only risk factor significantly associated with HIV infection, it is likely that these women are being infected by their spouses. This underscores the need for strengthening partner-notification strategies and counseling facilities in India.     

A graduating medical school class evaluates their educational experience

CONTEXT: Comparatively little is known about how U.S. adult men's attitudes and characteristics influence their decision to use contraceptives to prevent pregnancy and to take actions to protect themselves from infection with sexually transmitted diseases (STDs). METHODS: Attitudinal and background data on 1,595 men from the 1991 and 1993 waves of the National Survey of Men (NSM) were used, through logistic regression techniques, to predict the likelihood of current contraceptive use to prevent pregnancy and recent efforts to avoid STD infection among men in three types of sexual relationship--marriage, cohabitation and dating. RESULTS: At the 1993 interview, 58% of men were using contraceptives to prevent pregnancy and 22% had recently taken actions to protect themselves from STDs. Men's concern about how easy a method was to use reduced the likelihood of STD protection, but had no influence on contraceptive use to prevent pregnancy; however, concerns about a method's risks to the female partner increased the likelihood of both outcomes. Couples in which the man expected his partner to take primary responsibility for contraception were 40% as likely to be protecting themselves against STDs as were couples in which the man believed he shared or had greater responsibility. Married men were the least likely to be protecting themselves against STDs, whereas men who were dating were the most likely to do so. CONCLUSIONS: Men's attitudes and characteristics were important predictors of contraceptive use to prevent pregnancy and of efforts to protect against STDs, even after controls for the female partner's characteristics were entered in the analysis. The findings emphasize the need to include men in interventions aimed at reducing unintended pregnancy and STD transmission.     

Ion channels, cell volume, and apoptotic cell death

BACKGROUND: Condylomata acuminata is one of the most common sexually transmitted diseases (STDs) diagnosed in the United States, yet relatively little research has been conducted on the determinants of this disease in well-defined populations. GOAL: To determine the exposures that predispose a woman to the development of condylomata acuminata or genital warts. STUDY DESIGN: A population-based case-control study was conducted among enrollees of Group Health Cooperative of Puget Sound. Patients (94 women with incident and 55 women with recurrent condyloma) were diagnosed between April 1, 1987 and September 30, 1991. Control subjects were 133 women without a history of genital warts. An in-person interview was conducted to collect information on subject characteristics, exposures, and on all episodes of genital warts. RESULTS: Women with five or more partners within the 5 years before reference date were over seven times more likely to have incident condyloma (relative risk [RR], 7.5; 95% confidence interval [CI], 3.1-18.1) and over 12 times more likely to have recurrent condyloma (RR, 12.8; 95% CI, 4.2-38.9) compared with women with only one sexual partner during this time period. An increased risk of incident condyloma was also associated with a history of any STD (RR, 2.6; 95% CI, 1.1-5.8), a history of oral herpes (RR, 2.2; 95% CI, 1.1-4.4), and a history of allergies (RR, 2.0 95% CI, 1.0-3.8). Our data did not support a strong association between risk of condyloma and smoking or recent use of oral contraceptives. CONCLUSION: Our results suggest that risk of condyloma is primarily related to sexual behavior. We did not observe a strong association between risk of condyloma and many of the exposures considered to be potential cofactors for anogenital cancers associated with other types of human papillomaviruses.     

Correction of the hypoplastic nasal ala using an auricular composite graft

OBJECTIVES: The study investigated if women with experience of casual travel sex, with a previously unknown man abroad, on different types of journeys (charter, vagabond, business and education trips), differ with regard to sexual risk behavior and history of sexually transmitted diseases (STDs). STUDY DESIGN: The study population consisted of 996 women. Of these, 27.7% admitted that they had had casual sex during journeys. The remaining women were used as a comparison group. History of STDs and sexual risk behaviors were investigated. RESULTS: The frequency of women who had more than ten lifetime sexual partners were greatly increased in all groups, as compared to the controls. A history of gonorrhea was most frequent among the charter travellers. A history of genital chlamydial infection was most common among the vagabond travellers. The lowest frequencies of a history of STDs was observed in women engaging in casual sex on 'business' journeys and they had significantly less often a history of STDs as compared to the charter travellers. A high frequency of STDs were seen in women who had experience of casual sex on different types of journeys. CONCLUSION: Women on business trips, although they had a similar sexual risk behaviour as the other groups of travellers, had less often a history of STDs.     

Enhanced immunogenicity of a recombinant genital warts vaccine adjuvanted with monophosphoryl lipid A

The regression of genital warts is believed to be a T-cell-mediated immune effect. We have sought to enhance the immunogenicity of a therapeutic vaccine for the treatment of genital warts with the use of the adjuvant monophosphoryl lipid A (MPL-immunostimulant), a detoxified form of the lipopolysaccharide (LPS) of Salmonella minnesota R595. The comparative immunogenicity and reactogenicity of a recombinant human papillomavirus type 6 (HPV6) L2E7 fusion protein in either aqueous, oil-in-water emulsions or Alhydrogel formulations containing MPL was evaluated. We conclude that the simple addition of MPL to the L2E7 fusion protein already adsorbed onto Alhydrogel preferentially enhances antigen specific in vitro T-cell proliferative responses, IFN gamma production and in vivo delayed type hypersensitivity responses without increasing its reactogenicity.     

Determinants of genital human papillomavirus infection among cytologically normal women attending the University of New Mexico student health center

OBJECTIVES: To confirm the risk factors for genital human papillomavirus (HPV) infection. GOAL OF THIS STUDY: To investigate risk factors for HPV detection apart from the correlated risk factors for cervical neoplasia. STUDY DESIGN: Cervical human papillomavirus (HPV) DNA was assessed in 357 cytologically normal women attending the University of New Mexico student health center. Cervical swab samples were obtained for HPV DNA detection and typing using a PCR-based DNA amplification system. Possible determinants of cervical HPV were examined including age, ethnicity, history of sexually transmitted disease, oral contraceptive use, smoking, age at first intercourse, lifetime number of sex partners, marital status, and history of pregnancy. RESULTS: A 44.3% overall prevalence of cervical HPV was observed. On univariate analysis, factors associated with increasing HPV prevalence included higher lifetime number of sex partners and single marital status. After adjustment for potential confounding variables, we found that HPV prevalence increased with higher lifetime number of sexual partners. CONCLUSION: These findings, along with those from the companion reports in this issue of the journal, support the sexual route of transmission of the virus.     

Effect of nonsteroidal anti-inflammatory drugs on the action of misoprostol in a regimen for early abortion

BACKGROUND AND OBJECTIVES: Because warts are often found in the male urethra, human papillomavirus (HPV) may well be present in urine of patients with urethral condylomata. GOAL: To detect HPV DNA in urine specimens of men with condylomata acuminata using polymerase chain reaction. STUDY DESIGN: Forty-seven urine specimens and 25 paraffin-embedded tissues of condylomata acuminata were obtained from men. Of the 47 urine specimens, 29 were from patients with urethral condylomata, 3 from patients with penile condylomata only, and 15 from control subjects without condylomata. Both L1 consensus primers and type-specific primers for-HPV 6, 11, 16, 18, and 33 were used. RESULTS: HPV DNA was detected in 22 of the 29 (76%) urine specimens from patients with urethral condylomata, in none of the 3 urine specimens from patients with penile condylomata, and in none of the 15 controls. Paraffin-embedded tissues of all 25 condylomas were positive for HPV DNA. The HPV types detected in urine were identical to those detected in urethral condylomas. CONCLUSIONS: HPV DNA is present in urine of patients with urethral condylomata. Urine may be used for noninvasive screening of asymptomatic HPV infections of the male genital tract. Detection of HPV DNA in urine may be useful for monitoring the response to treatment of urethral condylomata.     

Risk factors for HPV detection in archival Pap smears. A population-based study from Greenland and Denmark

The most important risk factor for cervical cancer is genital infection with certain types of human papillomavirus (HPV). The presence of HPV was studied in archival smears from a random sample of women living in Greenland (GW) and Denmark (DW) having, respectively, a high risk and an intermediate risk for cervical cancer. Risk factors were also examined of the original 126 Danish and 129 Greenlandic archived smears collected during October and November 1988. 125 were located from each country including all abnormal smears. HPV DNA was isolated from the smears and detected by means of a consensus polymerase chain reaction (PCR) detecting a broad spectrum of genital HPV types. HPV was detected in all the abnormal smears and in 22 and 33% respectively of the cytological normal smears from DW and GW. Risk of HPV was significantly higher in smears from women who started sexual life relatively recently (respectively, < or = 4 and < or = 6 years ago in DW and GW) compared with > or = 10 years ago (adjusted prevalence-OR: 9.3; 95% CI: 2.2-39.2 in DW and 5.9; 95% CI: 1.4-25.3 in GW). Among other important risk factors were age in both areas, lifetime number of sex partners and current smoking in DW and ever and gonorrhoea in GW. This study confirms the usefulness of the method as all abnormal smears were positive and, furthermore, the predictors for HPV presence in the normal smears corroborate with those found in recent studies of HPV in fresh cervical swabs. Thus, this method can be useful for large-scale epidemiological studies of HPV DNA in already sampled material.     

STD/HIV prevention in Turkey: planning a sequence of interventions

This study was initiated to assess which mix of early STD/HIV prevention interventions would potentially be effective, cost-effective and sustainable in Turkey; and to program an intervention sequence to maximize synergy among the interventions. During rapid assessment we: 1) reviewed past issues of 3 leading newspapers; 2) collected information on TV coverage; 3) interviewed key informants including taxicab drivers, hotel employees, grocery store owners, academicians in public health and law, investigators of STD/HIV and reproductive tract infections, and officials in the ministry of health; 4) reviewed available evidence on STD/HIV morbidity, sexual behavior patterns, migration patterns and same/opposite gender sex trade. We found: 1) discrepancies between decision makers' perceptions and social realities with respect to the epidemiology of sexual behavior and STDs, and the state of public health programs; 2) discrepancies between sexual practices and public expression regarding sexual practices; 3) economic, demographic, and political pressures in Turkey and in surrounding countries for the expansion of prostitution; 4) a sexual double standard and gender specific migration patterns which sustain a high demand for commercial sex; 5) patterns of health care seeking behaviors and provision of STD clinical services which indicate other STDs may play a very important role in spread of HIV infection; 6) an important mass media role in opinion formation; 7) consensual denial of risk for the majority based on beliefs embedded in machismo, nationalism and religion, and a resulting marginalization and externalization of STD/HIV risk; 8) high prevalence of syphilis among both Turkish and immigrant female prostitutes in Istanbul (early latent 8 and 13%; late latent 0 and 4%; previous history 9 and 22%) 9) and high rates of syphilis among male prostitutes (early latent 11%, late latent 21% and previous history 58%). We concluded that interventions should initially include, in the following order; 1) awareness raising for decision makers and opinion leaders including members of parliament and mass media; 2) awareness raising for members of the general population; 3) needs assessment and intervention development for sex workers; 4) training in HIV and other STDs for medical personnel; and 5) quality assurance and control for laboratory procedures for STDs/HIV.     

Absence of human papillomavirus DNA in the plume of erbium:YAG laser-treated warts

BACKGROUND: The erbium:YAG laser (Continuum Biomedical, Dublin, Calif.) is a new resurfacing and ablating laser that produces minimal residual thermal damage. Laser safety requires careful attention to the hazards of the laser plume. It is important to know whether viable organisms survive in the vapors. Human papillomavirus (HPV) DNA has been detected in the vapor of carbon dioxide laser-treated and electrodesiccated human warts. The presence or absence of HPV DNA in the laser plume of erbium:YAG laser-treated warts has not been previously studied to our knowledge. OBJECTIVE: Our purpose was to determine the presence or absence of HPV DNA in the laser plume of erbium:YAG laser-treated human warts. METHODS: One half of clinically typical and histopathologically confirmed verrucae vulgares from five patients were submitted for HPV DNA detection with in situ hybridization. After erbium:YAG laser ablation of the remainder of the warts, the laser plume was deposited on the handpiece as an abundant fluffy material and was submitted for evaluation of HPV DNA by polymerase chain reaction with consensus primers for the HPV type detected in the wart specimens. RESULTS: HPV2 DNA was found in all warts. HPV DNA was not detected in the erbium:YAG laser plume after ablation of these same warts. CONCLUSION: The absence of HPV DNA in the plume of erbium:YAG laser-treated warts is a significant safety feature of this laser.     

External genital warts: report of the American Medical Association Consensus Conference. AMA Expert Panel on External Genital Warts

A consensus process was undertaken to describe and evaluate current information and practice regarding the diagnosis, treatment, and evaluation of patients with external genital warts (EGWs) and their sex partners. This process developed a number of key statements that were based on strong evidence in the literature or reasonable suppositions and opinions of experts. Key statements included the following. In most cases, EGWs can be diagnosed clinically by visual inspection. No one treatment is ideal for all patients or all warts. Women with EGWs and female sex partners of men with EGWs are at increased risk for human papillomavirus-related cervical disease and, like all women, should be screened for cervical cancer. The diagnosis of EGWs in children requires a sexual abuse evaluation. Clinicians who treat EGWs have a responsibility to counsel patients and to provide information about the infectivity, diagnosis, treatment, and natural history of EGWs and general information about sexual health and other sexually transmitted diseases.