Genital warts are fleshy growths or lumps found around the genitals and anus. They are caused by the human papillomavirus (HPV). Although warts that occur elsewhere on the body are caused by different types of HPV, contact with these warts does not cause genital warts. 

HPV can live in the vagina, vulva (Pic. 1), cervix, anus (Pic. 2) or penis (Pic. 3) and sometimes the mouth or throat and is spread through direct skin to skin contact with a person infected with HPV. This occurs most commonly through sexual contact and can occur even when there are no visible warts. This explains why genital HPV infection spreads easily among sexually active people. HPV may also be passed from mother to baby during labour and birth.

Transmission rate of genital warts is nearly 65%. After transmission of the virus, the HPV incubation period ranges from 3 weeks to 8 months; however, most warts appear 2 to 3 months after an HPV infection. Some people will feel upset about having HPV or genital warts. Often people feel anger toward their sexual partner, even though it is usually not possible to know exactly when or from whom the HPV was contracted. A diagnosis of genital warts does not necessarily indicate that partner has had another partner recently.

In most cases, the presence of warts can be confirmed by checking the genital area. Performing an anoscopy (look inside of your anus and rectum using anoscope) or examining the anal canal with a speculum may be required to thoroughly check warts inside the anal canal, the vagina, or the cervix. A biopsy may also be necessary in the event that a wart seems abnormal, has an abnormal color, or is resistant to the treatment, or in people with weakened immune systems. There is currently no blood test or swab test available to detect HPV infection. 

There is no cure for HPV infection, although in many people warts and HPV infection go away on their own without any treatment. Various treatments are available that may be useful if warts are unsightly or causing discomfort. Changes in the cells of the cervix caused by HPV infection can also be treated. Warts are harder to treat in a person with an impaired immune system, such as someone living with HIV (human immunodeficiency virus). 

Associated diseases

HPV

Genital warts are a clinical manifestation of HPV types 6 and 11, and are estimated to affect 1% of sexually active adults aged between 15 and 49. HPV infection is also strongly associated with cervical cancer, and is prevalent in as many as 99% of cases.

Evidence suggests that the former pathway may be involved in fertility alteration. Recent evidence suggests that HPV infection may affect fertility and alter the efficacy of assisted reproductive technologies. In men, HPV infection can affect sperm parameters, specifically motility. In patients undergoing intrauterine insemination (IUI) for idiopathic (unexplained) infertility, HPV infection confers a lower pregnancy rate. However, the role of HPV as a direct cause of infertility remains uncertain.

HIV

Human immunodeficiency virus (HIV) causes AIDS, which is the most advanced stage of HIV infection. HIV occurs as two types: HIV-1 and HIV-2. Both types are transmitted through direct contact with HIV-infected body fluids, such as blood, semen, and genital secretions, or from an HIV-infected mother to her child during childbirth.

HIV infection is known to alter the natural history of HPV infection. Patients co-infected with HIV-1 and HPV have a greater likelihood of HPV progression, with an increased risk for development of cervical neoplasia (cancer) in immunosuppressed women.

Complications

Genitourinary tract cancer

Genital HPV infections are connected with more than 99% of cervical cancers, 97% of anal cancer, 70% of vaginal cancers, 47% of penile cancers, 40% of vulval cancers, 47% of oropharynx cancers and 11% of oral cavity cancer cases. However, the mechanism of cancer progression in patients with HPV infection is not well established. Cancer and its treatment can sometimes affect an ability to have children.

Psychosocial aspect

Although genital warts are not life-threatening, they cause significant psychosocial harm. It is observed that testing positive for HPV and having a visible lesion or a cytological abnormality may have an adverse psychosocial impact, with increased anxiety, distress, and concern about sexual relationships. Negative feelings included fear and anxiety about cancer and becoming ill, concerns about fertility, feelings of being unclean because of the sexually transmitted nature of HPV, concerns about transmission and sexual relationships, a negative impact on feelings about sex, and relationship issues including blaming a partner for the infection. The risk of disease progression has also an impact on sexual health.

Warts in pregnancy

During pregnancy, especially between 12th and 14th weeks of pregnancy, genital warts may grow fast. These warts may sometimes become very large particularly when new warts develop during pregnancy. Compared to non-pregnant women, these warts get larger in pregnant women. 

Pregnancy increases activities of HPV, resulting from decreased cellular immunity and increased blood flow and number of vessels in the genital area that occur due to pregnancy. Furthermore, the mentioned warts are fragile during pregnancy and usually cause itching and bleeding. In some cases, warts may exceptionally enlarge and block the birth canal. In such cases in which a patient may suffer from excessive bleeding or labor dystocia (obstructed labor), performing a cesarean section is suggested.

Although epidemiological studies do not indicate that performing cesarean section has any protective effects, cesarean sections are usually recommended in the case of premature rupture of membranes or high viral load. Another risk factor in cases of genital warts is bacterial infection caused by entrapment of bacteria which may cause chorioamnionitis (infection of the chorion and amnion during pregnancy) and fetal infection like when premature rupture of membranes occurs. Recently, several studies mentioned that preterm delivery and placental disorders occur as a result of HPV viral oncogenes.

When cervical HPV infection is considered instead of placental or abortive tissue infection, significant association is found between HPV positivity and premature rupture of membrane. If HPV infection weakens the membrane, it could lead to miscarriages. In fact, HPV trophoblasts infection corrupts the embryo’s health and its ability to invade the uterine wall. Even if cervical HPV infections can remain silent without cellular lesions, infected women can bear a healthy embryo but they should be paid more attention because of virus transmission to babies, a membrane premature rupture or miscarriage risks.

Mother-to-child transmission

HPV can be transmitted from a mother to her fetus during labor. This may cause lesions in the conjunctival (inside of the eyelids), oral, and/or anogenital (anus and genitalia) area in the neonatal period. Prenatal transmission of the virus, Types 6 and 11, rarely causes juvenile laryngeal papilomatosis (JLP; warty growths on the vocal cords in children and young adults). In such cases, the possibility of performing a cesarean section should be discussed with the mother who has warts at the time of delivery.

Risk factors

  • having unprotected sex with multiple partners
  • having had another sexually transmitted infection
  • having sex with a partner whose sexual history you don't know
  • becoming sexually active at a young age
  • smoke
  • having immune system weaknesses
  • having a history of child abuse
  • mother-to-child transmission

Female fertility

Although the presence of human papilloma virus (HPV) by itself doesn’t affect your ability to get pregnant, it can cause other problems that may lead to infertility, if left untreated. It has been suggested that HPV has an important role on the development of cervix, vaginal and vulva cancers. These effects are long term and they can only be started by an HPV type with oncogenic effects. This could make woman infertile or affect her ability to carry a full-term pregnancy, because cancer treatment can leave scarring on the cervix, which may stop sperm from entering the uterus and fertilizing eggs.

Also, treatment of cervical cancer can also weaken a woman’s cervix, especially if a lot of tissue needs to be removed. The woman may end up with a condition called incompetent cervix. Even if an egg is fertilized and pregnancy is achieved, the cervix might open before it’s time to give birth and thus miscarriage is more likely.

Male fertility

It is now well established that HPV infections in men result in semen contamination. Several epidemiological studies revealed that HPV is more prevalent in infertile men or those with leukocytospermia compared to fertile ones. It was shown in many cross-sectional and case-control studies that HPV infection is associated to poor semen quality. In effect, semen infection by HPV was significantly associated to reduced cell viability, reduced cell mobility, reduced amplitude of lateral head displacement, decreased cell count, decreased amount of normal morphology cells and the increased level of anti-sperm antibodies in semen.

Since HPV is a sexually transmitted, it is highly contagious that even condom use may not be protective. Unprotected areas of male genital may be the contact for transmission during sexual contact. Therefore, it is important to avoid sexual relationships with the ones who have clearly visible genital warts.

The vaccine can prevent infection caused by the four most common types of genital HPV. Two of the HPV types in the vaccine protect against the majority of genital HPV related cancers while the other two protect against the genital HPV types which cause 90% of genital warts. It does not protect against cancers and genital warts caused by the HPV types not included in the vaccine.

Genital warts vary somewhat in appearance. They may be either flat or resemble raspberries or cauliflower. The warts begin as small red or pink growths and grow as large as four inches across, interfering with intercourse and childbirth (in some cases). 

The warts grow in the moist tissues of the genital areas. In women, they occur on the external genitals and on the walls of the vagina and cervix; in men, they develop in the urethra and on the shaft of the penis (Pic. 4).

Symptomatic warts can be seen in about 1% of the population aged 15 to 49 years. However, many people who have been exposed to the virus do not develop visible warts because their immune system keeps the virus under control.

Topical treatment

Podophyllotoxin is a good medical substance derived from podophyllin, which is available in the form a pure standard product. The use of podophyllotoxin cream is appropriate for the treatment of anogenital warts in female patients. This medical cream should be used twice a day, 3 times a week, followed by a 4-day rest period. These cycles should be repeated weekly for 4 weeks. Large wart areas (10 cm or more) should not be treated at once because when these areas become necrotic, they cause pain.

At bedtime, a patient should apply this cream to the clean and dry skin in the location of the lesion, rub it until the cream disappears, and leave the cream on the area for 6 to 10 hours. Afterwards, the area should be washed off with water and mild soap. Because this cream undermines the protective effects of condoms and diaphragms, the patient should not have sexual intercourse until the cream is on the skin.

One of the often prescribed creams is Aldara. Aldara should be used 3 times a week for up to 16 weeks. Mild local inflammatory reactions including erythema, bumps, sores, rashes, and blisters may be seen as signs of using this cream. Lesions are completely removed in 40% to 50% of women; however, in 30% of cases, lesions recur after 12 weeks.

The psychological stress of having genital warts is often greater than the morbidity of the disease, and therefore successful treatment is crucial.

Current treatment for genital warts is less than satisfying. No clear ideal therapy has been identified. Locally destruction methods have mainly included surgical excision, electrocautery, cryosurgery and laser vaporization, which may result in scarring and are associated with recurrence. Chemical destructive methods using various acids, such as trichloroacetic or bichloroacetic acid, can be applied by the patients but are often locally irritating and not uniformly effective. Podophyllum resin, Podophyllotoxin, immune inducers (e.g., imiquimod), 5-fluorouracil cream can be used as a topical treatment. However, these medications require several weeks of treatment and may also irritate the skin.

Recurrent lesions are usually treated through reapplying the method that led to the initial removal of the lesion. Reapplying the previously used method is very likely to be successful.

Pharmacotherapy

TCA

90% to 99% trichloroacetic acid (TCA) is a solution used for small and separate lesions. It should be applied directly and sparingly to each wart. The treated area should be washed twice a day. The area is checked in the seventh day of the treatment. TCA is a destructive and caustic substance that should be applied by experienced professionals.

Surgical therapy

In the case of large lesions (> 20 cm2) or bulky lesions, because medical treatments need a long period of time and are often incomplete and hard to bear, surgery is recommended as an initial treatment. Surgical methods used to treat genital warts include curettage, electrosurgery, and application of a scalpel under general or local anesthesia. Patients with multiple or large warts of any location should be referred for surgical treatment under general anesthesia.

Treating genital warts does not cure infection with human papillomavirus (HPV), the virus that causes genital warts. The virus may remain in the body in an inactive state after warts are removed. A person treated for genital warts may still be able to spread the infection.

Other therapies

Cryotherapy

Cryotherapy destroys genital warts by freezing them with liquid nitrogen. Cryotherapy is used for a wide range of lesions. It can be applied in closed systems by using nitrous oxide or spraying liquid nitrogen directly. The cold is usually applied for 10-20 seconds. The size and thickness of the warts determine the number and length of freeze/thaw cycles. Up to three treatments may be needed.

If conservative medical treatments fail to achieve a full term pregnancy, the physician may suggest the patient undergo in vitro fertilization (IVF). 

In vitro fertilization (IVF) and artificial insemination are medically assisted solutions for conception in many infertile couples. These approaches are proposed to couples for which semen parameters are altered or infertility is due to cervical hostility to spermatozoa. Considering the fact that HPV is associated with altered semen parameters, in vitro fertilization and embryo transfer could be considered a viable alternative in cases of reduced fertility associated with semen HPV infection. 

It is well known that sperm cells adsorb HPV particles preferentially in two distinct sites along the equatorial region. This adsorption does not abrogate the fertilization potency of sperm cells but, it is unclear whether HPV infection has effect on steps following fecundation.

IVF and ART generally start with stimulating the ovaries to increase egg production. Most fertility medications are agents that stimulate the development of follicles in the ovary. Examples are gonadotropins and gonadotropin releasing hormone. After stimulation, the physician surgically extracts one or more eggs from the ovary, and unites them with sperm in a laboratory setting, with the intent of producing one or more embryos. Fertilization takes place outside the body, and the fertilized egg is reinserted into the woman's reproductive tract, in a procedure called embryo transfer.

Intracytoplasmic sperm injection (ICSI) is beneficial in the case of male factor infertility where sperm counts are very low or failed fertilization occurred with previous IVF attempt(s). The ICSI procedure involves a single sperm carefully injected into the center of an egg using a microneedle. With ICSI, only one sperm per egg is needed. Without ICSI, you need between 50,000 and 100,000. 

Surrogacy via a gestational carrier is also an option when a patient's medical condition prevents a safe pregnancy, when a patient has ovaries but no uterus due to congenital absence or previous surgical removal, and where a patient has no ovaries and is also unable to carry a pregnancy to full term.

Find more about related issues

Sources

Assisted reproductive technology ―sourced from Fertilitypedia licensed under CC BY-SA 4.0
Genital Warts and Human Papillomavirus (HPV) ―sourced from Queensland Government licensed under CC BY 3.0 AU
Genital Warts ―by Akhavan et al. licensed under CC BY-NC 4.0
SOA-Condylomata-acuminata-around-anus ―by unknown licensed under CC BY-SA 3.0
SOA-Condylomata-acuminata-female ―by SOA-AIDS Amsterdam licensed under CC BY-SA 3.0
SOA-Condylomata-acuminata-man ―by SOA-AIDS Amsterdam licensed under CC BY-SA 3.0
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