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HPV and Genital Warts

Human Papillomavirus (HPV) are DNA viruses with more than 100 subtypes of which more than 40 infect the skin and mucosa of the anal-genitalia region.

Genital warts also known as Condylomata Acuminata are due to “low risk” subtypes 6 & 11 rarely associated with genital cancers. Whereas high risk subtypes like 16, 18, 31 & 33 are associated with cervical and genital cancers.

HPV virus is transmitted by direct contact during sexual intercourse with affected partner. The incubation period can range from weeks to years.
Clinical presentation of Genital Warts

Genital warts are multifocal usually 5-15 ranging from 1 to 10 mm in diameter which will increase in size. They can appear as exophytic, filiform or flat. The large exophytic warts resemble cauliflower hence sometimes it is described as “cauliflower-shaped” warts. They usually occur at areas with high friction during sex.

Subclinical lesions may only be visible after application of acetic acid and with magnification. Genital warts may increase in numbers and size during pregnancy. There is always a risk of spreading to the neonate during delivery hence affected mothers should be treated.

The cancerous subtypes 16 & 18 may present as genital cancers or cervical cancer in women.

Tests to confirm HPV genital warts

1.5% acetic acid application: subclinical /discrete warts usually turn white (acetowhite) after application of 5% acetic acid on them for 3 minutes. However this effect will also appear in patients with abrasions or non-specific inflammation or candida infection hence it is not specific for HPV warts.

2.Skin biopsy: This is recommended for lesions with uncertain diagnosis, atypical features, bleeding, and abrasions or unresponsive to treatment.

3.HPV DNA detection: can be done with 2 methods namely Hybrid Capture II (HC II) and the polymerase chain reaction (PCR) enzyme immunosorbent assay.
Treatment of HPV Genital Warts

Currently there is no treatment modality is completely satisfactory that eliminates HPV. Genital warts have different respond to the different treatment modalities. The goal of treatment is to remove all visible exophytic warts and not the eradication of HPV.

It is important to examine for anal warts and to pull back the foreskin to look for possible hidden warts. For females with genital warts, a speculum examination of the cervix and a Pap smear as HPV increases the risk of cervical cancer.
Home topical treatment of HPV genital warts

1.Podophylotoxin 0.15% cream
This is a purified extract from the podophyllum plant.It is to be applied onto the warts twice daily for 3 days and then rest for 4-7 days. Then repeat the cycle.Usually about 60-80% cases clear after repeating 1-4 courses of application.
Recurrence rates range from 7 to 38%. Common side effects include: redness of skin, pain, erosions and transient burning after first course only starting from day 3.This method is contraindicated in pregnant women.

2.Podophylin 0.25% or 0.5% solution
It is same as the cream form, the solution is applied onto the warts twice daily for 3 days then rest for 4 days and repeat cycle. It is also contraindicated in pregnant women. It is not expensive and effective method.

3.Imiquimod 5% cream
It acts as an immune response modifier. The cream should be applied 3 times a week at bedtime and washed off the next morning. It should be continued till the wart has cleared, up to a maximum of 4 months.

Recurrence rates range from 10-15%. Clearance is about in 56% cases, higher clearance in women and men who is uncircumcised.It is contraindicated in pregnant women.
Sexually transmitted disease clinic treatment of HPV warts

1.Cryotherapy
Liquid nitrogen is used to cause epidermal and dermal necrosis and thrombosis of vessels. This procedure is very safe and, simple and inexpensive. It should be done once every one to two weeks.

Side effects include some pigmentary changes, inflammation, scars and also blister formations. It is safe to be used in pregnancy. The initial response rate ranges from 63% to 89%. 
2.Trichloroacetic Acid (50-80%)

This is a causative agent that causes cellular necrosis.A small amount of it is applied to the wart avoiding normal skin at weekly intervals.When the product dries up, white frosting will form over it.


Talc or sodium bicarbonate can be used to dust the area to prevent further damage. Any excess unreacted acid should be washed off.It is not effective for large warts and repeated sessions are not well tolerated.The initial response rate ranges from 70-80% and the recurrence rate is about 36%. The side effects are burning sensation post application, scarring (rare) and ulcers.

3.Electrosurgery

Under local anesthesia, the warts are removed. Mask and smoke evacuator should be used.This is effective for pedunculated warts and keratinized warts
4.Carbon Dioxide laser ablation

Local anesthesia is applied on affected area and carbon dioxide laser is used to ablate the warts. Mask and evacuator should be used. This is very effective treatment with minimal tissue damage and has good healing results within 2-4 weeks.This is the preferred method for warts at sensitive areas like cervix and vagina. However it is costly.

5.Snip or shave excision of warts

Using scissors or scalpel, the warts are excised out under local anesthesia.Suturing post excision is not required. It effectively eliminates warts at first visit. Recurrence rate is about 20-30%.
Recommended treatments for different HPV sites

Anal Warts: Cryotherapy or surgical excision or electrocautery or trichloroacetic acid can be used for treatment of warts around the anal canal.

Meatal Warts: Warts around the meatus of the penis can be treated with Podophylotoxin cream/solution or electrocautery or cryotherapy. If the warts are too extensive, urologist consult is warranted.

Cervical Warts: Cervical cancer should be ruled out before starting treatment.  A Pap smear KIV colposcopy should be done first. Treatment modalities include carbon dioxide laser ablation or electrocautery or cryotherapy. Topical treatments are not recommended.

Vaginal Warts: Carbon dioxide laser or electrosurgery or cryotherapy or trichloroacetic acid can be used to treat warts around this area. 
Treatment of Genital Warts in pregnancy

There is a risk of 1 in 400 chance of transmission to the infant during delivery leading to laryngeal papillomatosis in neonates. Hence all genital warts should be removed in pregnancy as they can proliferate and become friable. Topical applications like Podophylin, podophyllotoxin and Imiquimod are all contraindicated in pregnancy.
HPV Vaccines

Currently there are vaccines available which act against specific HPV subtypes. Gardasil by Merck is a quadrivalent vaccine against HPV 16&18 (cancer causing subtypes) and HPV 6&11 (which accounts for 90% genital warts). Cervarix by GSK prevents infection against HPV subtypes 16&18 (accounts for 70% of cervical cancers).

The vaccines are most effective if taken before first sexual intercourse. The vaccines do not contain live virus or any HPV DNA hence it neither induces the condition nor cause infections.

The vaccines are injected into the muscles at intervals of 0, 1 or 2 and 6 months. A total of 3 vaccine shots will complete the immunization. Currently there are no data on whether booster jabs are necessary.

The common side effects from the vaccines are soreness at injection site associated with mild swelling. Long term safety effects are still being evaluated.

As the vaccines do not protect against other subtypes that may also cause genital cancers, regular check-ups and pap smears are still recommended.

General advice on HPV Genital warts

1.Smokers have higher risk of HPV infection hence smoking cessation should be encouraged.

2.The warts should clear by 3 months if there is consistency in treatments.

3.Female patients with HPV should have routine pap smear as HPV has been associated with cervical cancer.

4.Condoms should be worn until the complete clearance of warts has been achieved.

5.All partners up till 6 months ago should be assessed for HPV and other sexually transmitted diseases.
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