Pirotta, Marie V. MBBS, MMED, FRACGP, PHD*; Stein, Alicia N. BSC (HONS), MBIOSTAT, PHD†; Fairley, Christopher K. MBBS, FRACP, PHD‡; Morrow, Andrea RN, RM§; Conway, E Lynne BSC (HONS), GRADDIPEPIBIOSTATS, PHD†; Chuah, John MBBS, BSC (MED) (HONS), FACHSHM∥; McCloskey, Jenny MBBS, DIPVENMPH, FACHSHM¶; McNulty, Anna MBBS, MMED (SEXUAL HEALTH)#; Waddell, Russell MBBS, BSC, FACHSHM**; Carter, Rob BA, BA (HONS), GRADDIPEPIPOP HEALTH, MADMINST, PHD††; Garland, Suzanne MBBS, FRCPA, FACSHP, FRANZOG, MD‡‡§§
THE INTRODUCTION OF THE QUADRIVALENT vaccine in the Australian school-based National HPV Vaccination Program has the potential to eliminate a substantial proportion of the health burden of genital warts. External genital warts (EGWs) are a common sexually transmitted viral disease,1 with self-reported annual mean incidence of 80/100,000 in UK general practices,2 and lifetime prevalence of approximately 4% in Australians aged 16 to 59 years1 and 11% in those aged 18 to 45 years in Nordic countries.3
Infection with human papilloma virus (HPV) may have a marked psychosocial impact. Three-quarters of women with HPV reported experiencing anger and depression and two-thirds shame.4 Our own research using an HPV-specific instrument found that a diagnosis of EGWs had the same degree of adverse psychosocial impact as a high grade cervical lesion requiring ablative treatment.5 Recent estimates of annual costs associated with EGWs are $171 million in the United States6 and 54.1 million euros in Germany.7
In Australia, the bulk of sexually transmitted infections (STIs) are managed through its 30,000 general practitioners (GPs). Overall, STIs form a small fraction of GPs’ clinical load: only 0.17 per 100 encounters8 and up to 1.17 per 100 patients in the age range 12 to 49 years when other sexual health problems are included.9 Regarding treatment of EGWs specifically, 57% of Australians seek assistance from GPs and 17% from sexual health clinics.1 These few dedicated sexual health clinics are staffed by approximately 100 sexual health physicians (www.abs.gov.au).
A range of treatments is available to treat genital warts10–13; however, there are limited data on treatment practices and resource use in the Australian sexual health setting. This is an important issue, as although EGWs pose little risk to physical well being, treatment is time and resource consuming, as many therapies are staff applied, and patients often require multiple visits to achieve resolution. This project aimed to explore treatment practices for EGWs in Australian sexual health clinics.
Materials and Methods
We undertook a retrospective audit of case notes from consecutive individuals who presented with a new diagnosis of EGWs to 1 of 5 major sexual health clinics in Australia. Clinics were invited to participate based on their diverse geographical catchment areas and size. Audited sites are shown in Table 1.
Eligibility criteria were patients aged 18 to 45 years inclusively, presenting with first ever episode of EGWs treated at that clinic from January 1, 2004. Excluded were patients who were immunocompromised, including HIV infection, or enrolled in an EGW treatment study.
Data were extracted by 1 author (A.M.). The first 20% of records at the first site were independently audited by a second author (M.P.). Inconsistencies in data interpretation were discussed and agreed upon to ensure consistent future data extraction.
We aimed to identify and audit 500 cases (100 consecutive patients per clinic). Deidentified data were collected regarding: gender, age, pregnancy, whether referred to or from the clinic for treatment, concurrent STIs, site of warts, number of visits and types of treatment used at presentation, and assessment of clearance at the final visit available for audit. Initial therapy was grouped as either monotherapy, with ablative treatment, other staff-applied topical therapy, or prescribed topical therapy, or combination of therapies. The final visit was defined as where no EGW treatment was recorded for the next year. Assessment of EGW clearance was clinically defined: either eliminated/largely eliminated or not eliminated. Eliminated or largely eliminated was defined as when the patient’s final visit strongly suggested that the chosen treatment would completely eliminate the EGWs and the patient was instructed to return only if the EGWs persisted.
We were not able to collect data to assess resources used in management of EGWs because of the diverse financial arrangements adopted at the 5 clinics for both consultations and treatments used. Ethics approval was obtained from the relevant Human Research Ethics Committees at each site.
Data were transferred to Stata Statistical Software, version 9, for generation of descriptive statistics and frequency histograms. For categorical variables, summary statistics presented include number and percentage. Median and range are presented to describe the continuous variables age, number of visits, and treatment period, as the data were not normally distributed.
Table 1 provides a description of the audited clinics, their relevant policies and practices regarding EGWs and total number of new cases of EGWs for the audit year. Four hundred eighty-nine case records meeting the inclusion criteria were audited. Forty-three percent (n = 209) of the sample were women, with 3% pregnant (n = 6). At 3 sites, women constituted approximately half of the audited patients; however, at the Sydney and Gold Coast clinics, women represented about one-third of cases.
The median age of cases at diagnosis (Fig. 1) was 23.2 years for women (range, 18.3-43.9) and 26.8 years in men (range, 18.2-44.8). The median length of time that warts were noted to be present before presentation was 4 days, range of 0 to 260 days.
One-fifth (96/489) of patients had been referred to the clinic for EGW treatment, 86% by their GP. Of these, 40 (42%) had received prior treatment: 29 (30%) had received 1 type of treatment, 10 (10%) people had received 2, and 1 (1%) patient had tried 4 different treatments. The commonest prior treatments used were cryotherapy (n = 23) and imiquimod (n = 15).
At presentation, 26% (127/489) of patients had another STI or reproductive tract infection diagnosed: most frequent diagnoses were genital herpes simplex infection (n = 21; 4%); molluscum contagiosum (n = 17; 3%); Chlamydia trachomatis (n = 14; 3%); or bacterial vaginosis (n = 14; 3%).
Total visits for EGW treatment in the audited group was 1166: median of 2, range of 1 to 10. For largely or completely eliminated EGWs (n = 292), the median number of visits was 2 (range, 1-12) with 130 (45%) having 1 visit, 69 (24%) 2 visits, 32 (11%) 3, and 61 (20%) more than 3 visits for treatment. The number of visits was similar for warts not eliminated at the final visit (n = 197): median 2 visits (range, 1-13), with 94 (48%) having 1 visit, 52 (26%) having 2 visits, 21 (11%) having 3 visits, and 30 (15%) having more than 3 visits.
Half (140/280) the men and 40% (84/209) of women attended only once. Overall, women had significantly more visits than men (Fig. 2), with a median of 2 and range of 1 to 11. Men had a median of 1.5 visits, with a range of 1 to 17 (P = 0.012; Wilcoxon rank sum test).
Most patients (458/489; 94%) had warts recorded in the medical record in only 1 location, 14/209 (7%) women and 14/280 (5%) men had warts in 2 separate locations, and only 2 women and 1 man had warts in 3 separate locations. In women (n = 209), warts were predominately located on the vulva (170; 81%), perineum (19; 9%), and perianal region (18; 9%); however, warts were also less commonly documented in the introitus (8; 4%), vagina (5), anus (3), and 1 each in the urethra, buttock, pubic area, and on the cervix. In men (n = 280), warts were mainly detected on the penis (224; 80%), anus (27; 10%), and the perianal region (22; 8%); other locations were urethra (6), pubic area (6), suprapubic area (5), urethral meatus (3), with 1 case each of warts on the scrotum, groin, or perineum.
The choice of initial therapy was varied. Ablative therapy was chosen for initial treatment in 335 (69%) of cases. Overwhelmingly, cryotherapy (n = 330; 99%) was chosen, either as monotherapy (n = 257; 78%), in combination with applied topical treatments (n = 16; 5%), or prescribed topical treatments (n = 59; 18%), or in combination with both prescribed and applied topical treatments (n = 3; 1%).
Table 2 shows the choice of treatment at first visit by gender, number of visits, number of months over which visits occurred, and outcome. In 20 cases, no treatment was recorded at the initial visit (Table 2). In the remaining 469 cases, 382 (81%) were initially treated with a single therapy, usually cryotherapy (n = 252; 54%) or podophyllotoxin (n = 103; 22%).
Other topical treatments were applied by staff in 10% of cases (n = 49), usually podophyllotoxin (98%). Podophyllotoxin was used as a monotherapy (n = 22; 45%), and was also used in combination with cryotherapy (n = 15; 31%), with a prescribed topical therapy (n = 9; 18%) and 3 patients (6%) had all 3 types of treatment at the first visit.
Topical treatments were prescribed or recommended in 35% cases (n = 173); 136 (79%) were prescribed podophyllotoxin; 29 (17%) imiquimod, with other topical treatments used infrequently. Most commonly, prescribed topical treatments were used as monotherapy (n = 102). Use of prescribed topical treatments varied markedly over the 5 audited clinics. Nearly 20% of newly diagnosed EGWs were prescribed imiquimod at MSHC, whereas none were in Adelaide and Gold Coast; Sydney treated 3% of its patients with imiquimod; and Perth 8%. Prescription of podophyllotoxin varied from a low of 7% at MSHC to 39% in Perth and 70% in Sydney. In total, as either an applied or prescribed treatment, as a monotherapy or in combination, podophyllotoxin was used in initial treatment in 36% (n = 174) of cases. In addition to these described therapies, in 60 cases topical anaesthetic agents were also applied or prescribed.
Regarding staff and modality use over the course of treatment, 55% of doctors (n = 376) used cryotherapy only, 23% a prescribed topical treatment only, 1% applied 1 treatment only, and 16% used a combination of treatments, including topical anaesthetic agents. Of nurses (n = 108), most used cryotherapy only (43%), with similar numbers using applied topical (18%) and prescribed topical treatments (14%), and 22% of nurses used a combination, including topical anaesthetic agents.
Approximately 60% of patients continued to attend the clinics until the warts were largely or completely resolved on clinical inspection at the final EGW-related visit, with little difference across the 5 clinics or by gender. Only 7 patients were referred to other services for further treatment of their EGWs, usually for surgical procedures or laser therapy.
This is the first study to provide a description of EGW treatment in Australian sexual health clinics, which manage approximately 17% of these presentations.1 Nearly half of the patients attended only once. Most patients were treated with monotherapy, usually cryotherapy or less often podophyllotoxin, with a wide variation across sites, possibly reflecting local budgetary decisions. We found no difference in wart resolution, as defined, by initial treatment chosen. The diagnosis and treatment of EGWs constitute a sizable proportion of clinical visits to the audited sexual health services. Our results help complete the picture of the burden of EGWs on Australian sexual health centers, before the introduction of the government funded quadrivalent HPV vaccine program.
Our peak ages for treatment (women, 20-24 years; men, 25-29 years) are similar to those in a US audit,14 whereas in the United Kingdom and Nordic countries, 20 to 24 years is the peak age for both genders.3,15
Australian management of EGWs in sexual health centers seems to be different to that in specialist settings in other countries. In UK genitourinary medicine centers, which manage approximately 80% of EGWs,16 while staff-applied therapies also dominated, Australians are more likely to initiate treatment with cryotherapy as monotherapy (68%) than in the United Kingdom, where only 29% of men and 26% of women received cryotherapy alone.15 This UK study also noted marked variation in treatments used for EGWs across centers. By contrast in France, imiquimod is commonest first-line therapy for new EGWs (40%).17
Australians also have fewer visits: a median of 2 visits over approximately 1 week. A mean of 3.1 doctor visits over 3 months is reported in the United States14; a German study found 6.7 visits over an average of 3.2 months18; whereas in the United Kingdom, the median visits for men was 3.02 and for women 3.97 for completed episodes of care.15 In 40% of our audited cases, patients did not have EGW clearance confirmed. Fewer visits to Australian specialist services may well be because of the fragmented nature of care for STIs in Australia; once EGWs are diagnosed and other STIs excluded, patients may choose or be encouraged to continue with home applied therapy19 or attend their GPs for further treatment until resolution.
Interpretation of our findings is limited by the study’s retrospective nature and the diverse practices and policies across the audited clinics. The 5 clinics are not homogenous in the populations they serve or their approaches to treatment of EGWs. Patients may have received treatment from other clinics between audited visits. Selection bias may be present as clinic staff members choose treatment according to the size and location of EGWs. Wart burden, a confounding factor in clearance time,20 was not measurable in our study. In addition, we cannot gauge another 2 important considerations: whether these 5 clinics are representative of practices in all Australian sexual health clinics, although together the group does represent a large proportion of sexual health clinics, and, how representative these patients are of the total pool of EGW in Australia, most of whom are managed in general practice.
The Australian National HPV Vaccination Program is targeting girls aged 12 and over, with a catch up component for the next 2 years for women aged up to 26 years (http://www.health.gov.au/cervicalcancer). As the first year’s cohort uptake has been just under 80%, the benefits of this program in decreasing the EGW burden in women should be apparent within a few years, leading to a sizable decrease in case load, and improving access to services.21 Less impact is expected in clinics serving largely male populations. Adequate access to services is an important aspect in control of STIs.22
Our study is limited to EGW treatment in sexual health centers and will certainly underestimate the true number of EGW-related consultations in Australia. Further research is needed to describe treatment in the Australian primary care sector, where it is estimated that 60% of people with EGWs attend for treatment.1
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