Sexually Transmissible Infections in Clinical Practice

15. A Young Woman with Genital Lumps

Alexander McMillan1, 2  

(1)

Department of Genitourinary Medicine, NHS Lothian, Edinburgh Royal Infirmary, Edinburgh, Uk

(2)

University of Edinburgh, Edinburgh, Uk

Alexander McMillanFormerly, Consultant Physician, part-time Senior Lecturer

Email: a.amcmm@btinternet.com

Abstract

A 20-year-old woman, Linda, attends you as her General Practitioner. For the past 2 weeks she has noticed several swellings in the genital area. These are painless, but mildly itchy. She has not noticed lumps elsewhere on her body and she has not had generalized itch. Her general health is good, she is not receiving any medication, and she has no significant past medical history. Her periods are regular, the most recent having been 1 week previously. For the past 4 months she has been in a regular relationship with a 22-year-old man who has not noticed any genital abnormalities. Condoms are almost always used for vaginal intercourse. About 7 months ago she separated from her previous partner with whom she had been in relationship for 3 years. She has had no other sexual partners.

A 20-year-old woman, Linda, attends you as her General Practitioner. For the past 2 weeks she has noticed several swellings in the genital area. These are painless, but mildly itchy. She has not noticed lumps elsewhere on her body and she has not had generalized itch. Her general health is good, she is not receiving any medication, and she has no significant past medical history. Her periods are regular, the most recent having been 1 week previously. For the past 4 months she has been in a regular relationship with a 22-year-old man who has not noticed any genital abnormalities. Condoms are almost always used for vaginal intercourse. About 7 months ago she separated from her previous partner with whom she had been in relationship for 3 years. She has had no other sexual partners.

15.1 What Conditions Would You Consider in the Differential Diagnosis?

Table 15.1 indicates the most common causes of anogenital “lumps.” Scabies would be an unlikely diagnosis as itch is not the principal feature in this case: it is mild, and localized to the genitalia. Lichen planus can be associated with itchy genital lesions, and usually, but by no means always, skin lesions are noted elsewhere. Condylomata lata may be the only feature of late secondary syphilis, but syphilis is uncommon in women in the UK.

Table 15.1.

Causes of anogenital lumps in women.

• Anogenital warts

• Molluscum contagiosum

• Normal anatomical features, such as pilosebaceous glands and vestibular papillae.

• Skin tags

• Scabies

• Seborrhoeic keratosis

• Lichen planus

• Condylomata lata (secondary syphilis)

 

The diagnosis is clinical. In this case, examination shows multiple cauliflower-shaped, fleshy, hyperplastic warts (condylomata acuminata) on the labia minora, at the introitus, and on the perineum (Fig. 15.1).1 The vagina and uterine cervix appear normal.

A978-1-84882-557-4_15_Fig1_HTML.gif

Figure 15.1.

Warts on labia minora and perineum.

Linda is very upset when she is given the diagnosis. She cannot understand why she but not her partner has warts.

15.2 What Information Do You Provide?

There is good epidemiological evidence that the virus causing the majority of anogenital warts – the human papillomavirus (HPV) types 6 and 112– is acquired sexually. Uncommonly in adults, anogenital warts are caused by HPV types 1, 2, or 4, the types associated with common skin warts, and have most likely been acquired through auto-inoculation.

There is evidence that most HPV types 6 and 11 infections are transient and that the majority are symptomless or produce lesions that can only detected by detailed clinical examination, facilitated by magnification. As anogenital warts can have a long pre-patent period – a median of 3 months – it is usually impossible to tell when an individual has acquired his or her infection. The appearance of HPV lesions during a long-term relationship does not necessarily indicate infidelity.

15.3 How Would You Manage the Warts in This Case?

Anogenital warts are caused by a virus for which there is no antiviral treatment. Although most anogenital warts in immunocompetent patients eventually undergo spontaneous regression (cell-mediated immune responses are important in this process), treatment is offered to the majority of affected individuals with moist hyperplastic condylomata acuminata to reduce the risk of secondary infection and to alleviate anxiety. It must be explained to the patient that treatment can be prolonged and that recurrence is common after the warts have been eradicated by treatment. She should be reassured, however, that the lesions will eventually regress permanently.

The exclusion, detection and, if required, treatment of other sexually transmitted infections in the affected individual and the sexual partner(s) are essential first steps (Cases 1 and 2). Before initiation of wart therapy, it is important to attend to any other local infection whether sexually transmitted or not. For example, in women, any cause of vaginitis or discharge must be discovered and eradicated, particularly trichomoniasis and candidiasis. Sometimes warts regress after local inflammation has been controlled.

Table 15.2 shows the most commonly used treatments for external anogenital warts.

Table 15.2.

Treatments for anogenital warts.

Treatment

Comments

Podophyllotoxin

Imiquimod

Cryotherapy

Trichloroethanoic acid

Electrosurgery

Scissor excision

Laser

Antimitotic agent. Self-application. Useful for treatment of hyperplastic warts; less useful for keratinized lesions. Avoid in pregnancy

Immunomodulatory agent. Self-application. Useful for hyperplastic warts; less useful for keratinized lesions. Safety in pregnancy not established, so avoid. Expensive

Ablative therapy. Useful for keratinized warts. Can be used in pregnancy. Clinic attendance necessary

Useful for small numbers of warts. Corrosive – care needs to be taken with its application. Not suitable for home use. Can be used in pregnancy

Useful for keratotic warts

Useful for keratinized pedunculated warts, especially in perianal region. Local or general anesthesia needed

Useful for extensive warts (general anesthesia required). Not available in the majority of sexual health clinics

Table 15.3 is a schedule for the treatment of external hyperplastic warts.

Table 15.3.

Schedule for the first-line treatment of external genital warts.

Hyperplastic external genital warts, less than 10 in number or less than 5 cm 2 in area:

Cryotherapy with liquid nitrogen, repeated at two-weekly intervals for five cycles

OR

Podophyllotoxin 0.5% solution or cream (men) or 0.15% cream (women) applied twice daily for 3 consecutive days per week for up to 5 weeks

More extensive external genital warts:

Podophyllotoxin lotion or cream

OR

Imiquimod 5% cream, applied three times per week for up to 16 weeks.

 

Linda opts for treatment with podophyllotoxin cream.

She should be instructed in the use of the cream, and preferably shown by the physician or nurse the method of application. It is also helpful to identify to her the warts that should be treated (normal anatomical structures can be mistaken for warts). Mild tenderness and burning are common, and Linda should be warned about this possible side effect.

She has considered changing from condoms to the combined oral contraceptive pill as contraception and wishes to know if it is necessary to continue condom use with her current partner. What is your advice?

It is reasonable to consider that he has already been infected with the virus – condom use has not been consistent. There are few data on which to inform your advice. However, there is some evidence that among men, the time to regression of penile warts is shorter among those who use condoms with their female partners than those who do not. This finding may be explained by the prevention of continued re-exposure to the virus. Condom use should therefore be encouraged.

She re-attends the clinic 5 weeks after initiation of therapy. The warts persist, but they have reduced significantly in number and size. Linda, however, is becoming impatient and requests an alternative treatment.

15.4 What Is Your Further Management?

If there is a partial response to initial therapy, a further cycle of the same can be used.

When there has been no response, however, a change to an alternative treatment is indicated: for example, cryotherapy to podophyllotoxin, or podophyllotoxin to imiquimod.

In this case, treatment is changed to imiquimod at the patient's request. What advice would you give?

The mode of action of imiquimod – stimulation of the immune system against the virus – is explained in simple terms, and it is stressed that an immediate effect on the warts may not be obvious (In one study, the median time to complete clearance of warts was 7 weeks).

A thin layer of imiquimod cream is applied to the wart area and allowed to remain on the skin for between 6 and 10 h (preferably overnight) before washing with soap and water. The cream is applied three times per week. If the patient develops marked pain or discomfort, it may be necessary to discontinue therapy. When symptoms have resolved, however, the drug can be re-introduced, although it may be helpful to reduce the frequency of application, for example, by instructing the individual to apply the cream once in the first week, twice in the second, and three times per week thereafter. Imiquimod cream may affect the latex condom, and Linda should be warned about this possibility.

Linda is prescribed a 4 week's supply of the cream and attends the clinic at the end of that time. She has had mild irritation around the warts, and some have regressed. She requests a further supply of cream.

As imiquimod may be used for up to a recommended maximum of 16 weeks, a further 1 month's supply is prescribed.

Linda has heard that warts can become cancerous and that she should have annual cervical cytological screening. How would you respond to this?

In the immunocompetent individual, malignant transformation of anogenital warts is rare. They are caused by HPV type 6 /11 which has a low potential risk for malignancy. Previously, annual cervical cytological examination was recommended in women with a history of anogenital warts. This is now known to be unnecessary, but she is advised to have smears at the nationally recommended time intervals. As there may be an increased risk of vulval and vaginal cancers in immunocompetent women who have had genital warts, the subsequent development of lumps should prompt medical review. In immunocompromised individuals, high-grade squamous intra-epithelial lesions (H-SILs) of the vulva, cervix, and anal canal are common and anogenital warts may become cancerous. More regular cytological cervical (and anal) screening is recommended in such individuals.

When she attends for review 1 month later, the warts have completely resolved, but although she is very much relieved, she would like to know the likelihood of recurrence. She also expresses concern about transmission of HPV to a future partner. She has separated from her partner, but has recently met a man with whom she wishes to start a relationship.

15.5 What Is Her Risk of Infecting Him, and Will Condom Use Prevent Transmission of HPV?

Warts may recur, but it is impossible to predict the likelihood of such an event. Recurrence is said to be more likely in those infected with multiple viral types, but testing for multiple infection is not routine. Interestingly, and consistent with its mode of action, the recurrence rate among individuals treated with imiquimod is lower than those treated by other methods.

Prevention of HPV infection is difficult. Genital warts are contagious, and, although lesions can be eradicated by treatment, there may be sub-clinical lesions from which HPV is shed either persistently or episodically. As judged by the detection of HPV DNA in cervico-vaginal samples, the median duration of viral shedding after infection is said to be 12 months. HPV DNA is no longer detectable in over 85% of women 18 months after infection. In the individual case, however, there is no means of ascertaining his or her infectivity.

There are conflicting data on the protective effect of condom use on HPV infection. The virus is transmitted by direct skin to skin or mucosal contact, and, as the virus is widespread in the anogenital region, it is unlikely that even consistent use of condoms will eliminate risk of infection. This theory has been substantiated in several studies. Other studies, however, have found that condom use protects against HPV acquisition, and there is now some evidence that the risk of acquisition of genital warts can be reduced.

Linda has heard that there is now a vaccine available for the prevention of HPV infection and asks for further information about this. What information is available about HPV vaccination, and who should be vaccinated?

Two vaccines are currently licensed for use: a bivalent vaccine (Cervarix®, GlaxoSmithKline) prepared from virus like particles (VLPs) of HPV 16 and 18, and a quadrivalent vaccine (Gardasil®, Merck) prepared from VLPs of HPV 6, 11, 16, and 18. For 5 years following vaccination, both vaccines show >90% efficacy in preventing persistent infection with the oncogenic types HPV 16 and 18, and the quadrivalent vaccine has about 99% efficacy in preventing infection with the HPV types associated with anogenital warts (types 6 and 11). In clinical trials, both vaccines have shown 100% efficacy in preventing cervical and vulval high-grade intra-epithelial lesions (H-SILs). These are prophylactic vaccines, however, and no protective effect against H-SIL is seen in those women who have already been infected with oncogenic virus types.

A vaccination programme is being rolled out in many industrialized countries. In the United Kingdom, girls aged between 12 and 13 years are being offered vaccination with the bivalent vaccine, and there is a 3-year catch-up programme in which girls aged 13–18 years will be offered vaccine. As the bivalent vaccine will not prevent acquisition of HPV 6 or 11, the impact of the vaccination programme on the incidence of anogenital warts is unlikely to be significant. Males are not included in the programme, although H-SILs and anal cancer associated with the oncogenic types of HPV occur, particularly among men who have sex with men who are HIV-infected. There is also the possibility of infection being transmitted from a man to an unvaccinated woman.

Three doses of vaccine are given over a period of 6 months and studies have shown that high antibody levels can be achieved. The period of protection after primary vaccination, however, is uncertain, and it is still unclear as to whether or not booster does of vaccine will be required.

Footnotes

1

Other morphological types of warts occur on the genitalia:

·              Papular warts, appear as flesh-colored papules.

·              Keratotic warts that are crusted, resembling skin warts. They tend to be found in dry areas such as on the external labia majora or pubic skin.

2

On the basis of nucleic acid studies, more than 100 types have been reported. Four of the most common HPV types that infect the genital tract are HPV-6, HPV-11, HPV-16, and HPV-18. The former two types are found in hyperplastic anogenital warts, and, as they are not associated with cervical cancer, are designated “low-risk” types. Types 16 and 18, however, are frequently detected in anogenital cancers and are classified as “high-risk” types. Infection with multiple viral types, however, is common.