External Genital Warts Epidemiology and Quality of Life Impact
Impact of human papillomavirus-related genital diseases on quality of life and psychosocial wellbeing: results of an observational, health-related quality of life study in the UK. Dominiak-Felden G, Cohet C, Atrux-Tallau S, et al. BMC Public Health. 2013 Nov 12;13:1065.
Background: Data on the psychosocial burden of human papillomavirus (HPV)-related diseases other than cervical cancer are scarce. The objectives of this study were to measure and compare the psychosocial burden and the impact on health-related quality of life (HRQoL) of HPV-related lower genital tract diseases and genital warts (GW) using several generic and disease-specific instruments.
Methods: Overall, 842 individuals with normal cervical cytology (n = 241), borderline nuclear abnormalities and/or mild dyskaryosis (n = 23), cervical intraepithelial neoplasia (CIN)1 (n = 84), CIN2/3 (n = 203), vulval intraepithelial neoplasia (VIN)2/3 (n = 43), GW (n = 186) and a history of GW (non-current) (n = 62) were included. The generic European Quality of Life Index Version 5D (EQ-5D) questionnaire was completed by patients with GW and VIN2/3. Sexual functioning was evaluated using the Change in Sexual Functioning Questionnaire (CSFQ). Psychosocial impact was measured in women using the HPV Impact Profile (HIP) questionnaire. HRQoL was assessed using a GW-specific questionnaire, the Cuestionario Especifico en Condilomas Acuminados (CECA) (completed by patients with GW and history of GW). For each instrument, scores were compared between groups using the Student’s t-test. In addition, utility loss due to GW and VIN2/3 was evaluated by comparing mean EQ-5D scores weighted by age and sex with the UK general population normal values.
Results: A significant psychosocial impact was found in women diagnosed with HPV-related genital diseases, particularly in those with GW. The health state of younger adults with GW was significantly impaired compared with UK normal values (mean EQ-5D index score 0.86 vs 0.94, p < 0.001 for 18-24-year-olds; 0.87 vs 0.93, p = 0.030 for 25-34-year-olds). VIN2/3 was found to have a significant negative impact on sexual functioning, and women with VIN2/3 had a highly impaired health state compared with women in the UK general population (weighted mean EQ-5D index score 0.72 vs 0.89, p < 0.001; weighted mean Visual Analogue Scale score 62 vs 85, p < 0.001).
Conclusions: HPV-related lower genital tract lesions and GW significantly impair psychosocial wellbeing and HRQoL. The psychosocial aspects of HPV-related diseases need to be considered when evaluating the potential benefit of HPV vaccination.
Economic and Humanistic Burden of External Genital Warts. Raymakers AJ, Sadatsafavi M, Marra F, et al. Pharmacoeconomics. 2012 Jan;30(1):1-16.
External genital warts (EGW) are a sexually transmitted infection caused by various strains of human papillomavirus (HPV). Several studies have described the direct and indirect costs of EGW, while others have reported on the burden of EGW in terms of the impact on the quality of life (QOL) of patients. The arrival of a quadrivalent HPV vaccine that protects against both cervical cancer and EGW requires a proper understanding of the impact of vaccines on costs and QOL. Using pre-defined search terms and inclusion/exclusion criteria, we performed a systematic review of the economic and humanistic burden of EGW. The focus of our review was on literature describing the direct and indirect costs of EGW per episode of care (EoC) or per year, as well as the impact of EGW on disease-specific, generic, or preference-based QOL measures. We also reviewed the literature on the national economic burden of EGW from the perspectives of different countries. Other aspects of EGW management that can inform economic modelling studies, such as length of EoC, number of physician visits and indirect costs, were also explored. Our review sheds light on the high economic and humanistic burden of EGW and important differences in the costs between men and women, as well as the differences in health resource utilization and costs across countries. Our study also highlights the dearth of information on the impact of EGW on the QOL and productivity of patients.
Human Papillomavirus and Genital Warts: A Review of the Evidence for the 2015 Centers for Disease Control and Prevention Sexually Transmitted Diseases Treatment Guidelines. Park IU, Introcaso C, Dunne EF. Clinical Infectious Diseases. 2015 Dec;61(8) S849–S855.
To provide updates for the 2015 Centers for Disease Control and Prevention sexually transmitted diseases treatment guidelines on human papillomavirus (HPV) and anogenital warts (AGWs), a review of the literature was conducted in key topic areas: epidemiology and burden of disease; transmission and natural history; diagnosis and management of AGWs; occupational exposure of healthcare workers; anal cancer screening among men who have sex with men (MSM); and HPV vaccine recommendations. Most sexually active persons will have detectable HPV at least once in their lifetime; 14 million persons are infected annually, and 79 million persons have prevalent infection. HPV is transmitted frequently between partners; more frequent transmission has been reported from females to males than from males to females. A new formulation of imiquimod (3.75% cream) is recommended for AGW treatment. Appropriate infection control, including performing laser or electrocautery in ventilated rooms using standard precautions, is recommended to prevent possible transmission to healthcare workers who treat anogenital warts, oral warts, and anogenital intraepithelial neoplasias (eg, cervical intraepithelial neoplasia). Data are insufficient to recommend routine anal cancer screening with anal cytology in persons living with human immunodeficiency virus (HIV)/AIDS or HIV-negative MSM. An annual digital anorectal examination may be useful for early detection of anal cancer in these populations. HPV vaccine is recommended routinely for 11- or 12-year-olds, as well as for young men through age 21 years and young women through age 26 years who have not previously been vaccinated. HPV vaccine is also recommended for MSM, people living with HIV/AIDS, and immunocompromised persons through age 26 years.
Trends in the Prevalence of Anogenital Warts Among Patients at Sexually Transmitted Disease Clinics—Sexually Transmitted Disease Surveillance Network, United States, 2010–2016. Mann LM, Llata E, Flagg EW, et al. Journal of Infectious Disease. 2019;219:1389–97.
Background. Approximately 90% of genital warts are caused by human papillomavirus (HPV) types 6 and 11. In the United States, HPV vaccination has been recommended for girls and women aged ≤26 years, and since 2011, for boys and men aged ≤21 years and for gay, bisexual, and other men who have sex with men (MSM) aged ≤26 years.
Methods. Data were obtained from 27 clinics participating in the STD Surveillance Network. Trends in the annual prevalence of anogenital warts (AGW) from 2010–2016 were described by sex and by the sex of sex partners.
Results. During 2010–2016, significant declines in the prevalence of AGW were observed in women aged <40 years, men who have sex with women only (MSW) aged <40 years, and MSM of all age categories. An inflection in trend in 2012 was noted for MSW aged 20–24 or 25–29 years and for MSM aged 20–24 years.
Conclusions. The observed declines in the prevalence of AGW suggest that HPV morbidity is declining among populations attending STD clinics, including MSW, MSM, and women. Declines in younger age groups are consistent with what would be expected following the implementation of HPV vaccination. However, declines were also observed in older age groups and are not likely to be the result of vaccination.
Systematic review of the incidence and prevalence of genital warts. Patel H, Wagner M, Singhal P, et al. BMC Infectious Diseases. 2013,13:39.
Background: Anogenital warts (AGWs) are a common, highly infectious disease caused by the human papillomavirus (HPV), whose high recurrence rates contribute to direct medical costs, productivity loss and increased psychosocial impact. Because of the lack of a systematic review of the epidemiology of AGWs in the literature, this study reviewed the published medical literature on the incidence and prevalence of AGWs.
Methods: A comprehensive literature search was performed on the worldwide incidence and prevalence of AGWs between 2001 and 2012 using the PubMed and EMBASE databases. An additional screening of abstracts from relevant sexual health and infectious disease conferences from 2009 to 2011 was also conducted. Only original studies with general adult populations (i.e., at least including ages 20 through 40 years) were included.
Results: The overall (females and males combined) reported annual incidence of any AGWs (including new and recurrent) ranged from 160 to 289 per 100,000, with a median of 194.5 per 100,000. New AGW incidence rates among males ranged from 103 to 168 per 100,000, with a median of 137 per 100,000 and among females from 76 to 191 per 100,000, with a median of 120.5 per 100,000 per annum. The reported incidence of recurrent AGWs was as high as 110 per 100,000 among females and 163 per 100,000 among males. Incidence peaked before 24 years of age in females and between 25 and 29 years of age among males. The overall prevalence of AGWs based on retrospective administrative databases or medical chart reviews or prospectively collected physician reports ranged from 0.13% to 0.56%, whereas it ranged from 0.2% to 5.1% based on genital examinations.
Conclusions: The literature suggests that AGWs are widespread and the prevalence depends on study methodology as suggested by higher rates reported from routine genital examinations versus those from treatment records. However, there remains a need for more population-based studies from certain regions including Africa, Latin America and Southern Asia to further elucidate the global epidemiology of this disease.
External Genital Warts Pathology and Risk of Malignancy
Risk factors for and prevention of human papillomaviruses (HPV), genital warts and cervical cancer. Chelimoa C, Wouldesb TA, Cameron LD, et al. J Infect. 2013 Mar;66(3):207-17.
Genital HPV infection is associated with development of cervical cancer, cervical neoplasia, anogenital warts, and other anogenital cancers. A number of reviews have primarily addressed the role of HPV infection in cervical carcinogenesis, and differences in human papillomavirus (HPV) subtypes found in cervical cancer cases by histology and geographical region. This review provides an informative summary of the broad body of literature on the burden of HPV, the risk factors for HPV infection, genital warts and cervical cancer, and preventive measures against these conditions in females. Studies have identified the main risk factors for genital HPV infection in females as follows: acquisition of new male partners; an increasing number of lifetime sexual partners both in females and their male partners; and having non-monogamous male partners. Cervical cancer screening and HPV vaccination are the primary measures currently recommended to prevent cervical cancer. There is also an ongoing debate and conflicting findings on whether male circumcision and condom use protect against HPV infection and subsequent development of HPV-related illnesses in females.
Risk of cancer in patients with genital warts: A nationwide, population-based cohort study in Taiwan. Cho CY, Lo YC, Hung MC, et al. (2017) PLOS ONE 12(8): e0183183.
Background: Condyloma acuminata currently affects around 1% of sexually active adults, and its incidence is increasing. The coexistence of genital warts (GW) and certain cancers and an association between human papillomavirus (HPV) and various malignancies have been reported. Therefore, we conducted this large national study to analyze the risk of malignancies among men and women with GW in Taiwan.
Methods and findings: Between January 2000 and December 2013, approximately 3 million patients were reported to the National Health Insurance Research Database of Taiwan. Of these patients, 21,763 were diagnosed with GW. In the same time period, a total of 213,541 cancer cases were reported to the registry, of which 1002 were recorded among patients with GW. The age-specific incidence rates of GW and standardized incidence ratios (SIRs) of malignancies compared to the general population were calculated. Women acquired GW earlier than men, with a mean age at diagnosis of 32.63±12.78 years. The highest incidence rate for both genders peaked at 20–29 years. Of the 1002 patients with GW and malignancies, the SIR was 1.95 (95%CI 1.83–2.07). The most markedly increased risk was found for HPV-related cancers, with a SIR of 9.74 (95%CI 3.70–15.77). Significantly elevated risks were also noted for smoking-related cancers, anogenital cancers, cervix in situ, colon, rectum, lung, kidney, and prostate cancers. Most cancers developed within 10 years after the diagnosis of GW.
Conclusions: Patients with GW have an increased risk of HPV-related cancers, especially anogenital malignancies in Taiwan. The elevated risk of other cancers highlights differences in exposure and risk factors among patients with GW compared to the general population. Cancer screening and HPV vaccination programs should be emphasized for at-risk patients.
Condylomata Acuminata (Anogenital Warts) Contain Accumulations of HIV-1 Target Cells That May Provide Portals for HIV Transmission. Pudney J, Wangu Z, Panther L, et al. J Infect Dis. 2019;219(2):275-283.
Background: Condylomata acuminata (anogenital warts [AGWs]) are prevalent in human immunodeficiency virus (HIV)–infected individuals and sexually active populations at risk for HIV acquisition and have been associated with HIV transmission. We compared AGW specimens to control tissue specimens for abundance, types, and location of HIV target cells and for susceptibility to HIV infection in vitro, to provide biologic evidence that AGWs facilitate HIV transmission.
Methods: We used immunohistologic staining to identify HIV target cells in AGW and control specimens. We also inoculated HIV in vitro into AGW and control specimens from HIV-negative men and assessed infection by means of TZM-bl and p24 assays.
Results: CD1a+ dendritic cells, CD4+ T cells, and macrophages were significantly more abundant in the epidermis of AGW specimens than control specimens. These HIV target cells also often appeared in large focal accumulations in the dermis of AGW specimens. Two of 8 AGW specimens versus 0 of 8 control specimens showed robust infection with HIV in vitro.
Conclusions: Compared with normal skin, AGWs contain significantly higher concentrations of HIV target cells that may be susceptible to HIV infection. Condylomata may thus promote HIV transmission, especially in the setting of typical lesion vascularity and friability. Prevention or treatment of AGWs may decrease the sexual transmission of HIV.
