Condylomata Acuminata (Genital Warts) (Clinical)

Overview

Epidemiology^[1–4,6]

• Human papillomavirus Human papillomavirus Human papillomavirus (HPV) is a nonenveloped, circular, double-stranded DNA virus belonging to the Papillomaviridae family. Humans are the only reservoir, and transmission occurs through close skin-to-skin or sexual contact. Human papillomaviruses infect basal epithelial cells and can affect cell-regulatory proteins to result in cell proliferation. Papillomavirus (HPV) ( HPV HPV Human papillomavirus (HPV) is a nonenveloped, circular, double-stranded DNA virus belonging to the Papillomaviridae family. Humans are the only reservoir, and transmission occurs through close skin-to-skin or sexual contact. Human papillomaviruses infect basal epithelial cells and can affect cell-regulatory proteins to result in cell proliferation. Papillomavirus (HPV)):
  • Most common sexually transmitted infection Sexually Transmitted Infection Sexually transmitted infections (STIs) are infections that spread either by vaginal intercourse, anal sex, or oral sex. Symptoms and signs may include vaginal discharge, penile discharge, dysuria, skin lesions (e.g., warts, ulcers) on or around the genitals, and pelvic pain. Some infections can lead to infertility and chronic debilitating disease. Sexually Transmitted Infections (STIs) ( STI STI Sexually transmitted infections (STIs) are infections that spread either by vaginal intercourse, anal sex, or oral sex. Symptoms and signs may include vaginal discharge, penile discharge, dysuria, skin lesions (e.g., warts, ulcers) on or around the genitals, and pelvic pain. Some infections can lead to infertility and chronic debilitating disease. Sexually Transmitted Infections (STIs)) globally
  • Affects 75% of sexually active adults in the United States at some point in their life
  • Prevalence Prevalence The total number of cases of a given disease in a specified population at a designated time. It is differentiated from incidence, which refers to the number of new cases in the population at a given time. Measures of Disease Frequency: 10%–20% in the United States
• Condylomata acuminata Condylomata Acuminata Condylomata acuminata are a clinical manifestation of genital HPV infection. Condylomata acuminata are described as raised, pearly, flesh-colored, papular, cauliflower-like lesions seen in the anogenital region that may cause itching, pain, or bleeding. Condylomata Acuminata (Genital Warts) ( CA CA Condylomata acuminata are a clinical manifestation of genital HPV infection. Condylomata acuminata are described as raised, pearly, flesh-colored, papular, cauliflower-like lesions seen in the anogenital region that may cause itching, pain, or bleeding. Condylomata Acuminata (Genital Warts)):
  • Incidence Incidence The number of new cases of a given disease during a given period in a specified population. It also is used for the rate at which new events occur in a defined population. It is differentiated from prevalence, which refers to all cases in the population at a given time. Measures of Disease Frequency:
    • 200 in 100,000 individuals in the United States
    • 130–160 in 100,000 individuals in Europe per year 
    • 160–289 in 100,000 individuals globally per year
  • Prevalence Prevalence The total number of cases of a given disease in a specified population at a designated time. It is differentiated from incidence, which refers to the number of new cases in the population at a given time. Measures of Disease Frequency: 1% in the United States
  • 80% of infected patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship are between 17 and 33 years of age.
  • Peak age at presentation: 22–24 years

Etiology^[1–5,11]

Condylomata acuminata Condylomata Acuminata Condylomata acuminata are a clinical manifestation of genital HPV infection. Condylomata acuminata are described as raised, pearly, flesh-colored, papular, cauliflower-like lesions seen in the anogenital region that may cause itching, pain, or bleeding. Condylomata Acuminata (Genital Warts) are specifically lesions created by HPV HPV Human papillomavirus (HPV) is a nonenveloped, circular, double-stranded DNA virus belonging to the Papillomaviridae family. Humans are the only reservoir, and transmission occurs through close skin-to-skin or sexual contact. Human papillomaviruses infect basal epithelial cells and can affect cell-regulatory proteins to result in cell proliferation. Papillomavirus (HPV).

• HPV HPV Human papillomavirus (HPV) is a nonenveloped, circular, double-stranded DNA virus belonging to the Papillomaviridae family. Humans are the only reservoir, and transmission occurs through close skin-to-skin or sexual contact. Human papillomaviruses infect basal epithelial cells and can affect cell-regulatory proteins to result in cell proliferation. Papillomavirus (HPV):
  • Non-enveloped capsid Capsid The outer protein protective shell of a virus, which protects the viral nucleic acid. Capsids are composed of repeating units (capsomers or capsomeres) of capsid proteins which when assembled together form either an icosahedral or helical shape. Virology viruses Viruses Minute infectious agents whose genomes are composed of DNA or RNA, but not both. They are characterized by a lack of independent metabolism and the inability to replicate outside living host cells. Virology
  • > 100 strains described, 40 cause anogenital lesions
  • Types 6 and 11 cause approximately 90% of cases.
  • Multiple HPV HPV Human papillomavirus (HPV) is a nonenveloped, circular, double-stranded DNA virus belonging to the Papillomaviridae family. Humans are the only reservoir, and transmission occurs through close skin-to-skin or sexual contact. Human papillomaviruses infect basal epithelial cells and can affect cell-regulatory proteins to result in cell proliferation. Papillomavirus (HPV) types may be present within the same warts Warts Benign epidermal proliferations or tumors; some are viral in origin. Female Genitourinary Examination (i.e., coinfection is possible).^[11]
    • These may include oncogenic types 16 and 18, which are high risk for vulvar cancer Vulvar cancer There are multiple different types of malignancies that can affect the vulva. The most common histologic type is squamous cell carcinoma (SCC), which accounts for approximately 75%-85% of all vulvar cancers. Vulvar Cancer.
    • No evidence that the high-risk types actually cause warts Warts Benign epidermal proliferations or tumors; some are viral in origin. Female Genitourinary Examination 
  • Approximately 60% risk of developing warts Warts Benign epidermal proliferations or tumors; some are viral in origin. Female Genitourinary Examination after infection with HPV HPV Human papillomavirus (HPV) is a nonenveloped, circular, double-stranded DNA virus belonging to the Papillomaviridae family. Humans are the only reservoir, and transmission occurs through close skin-to-skin or sexual contact. Human papillomaviruses infect basal epithelial cells and can affect cell-regulatory proteins to result in cell proliferation. Papillomavirus (HPV) type 6 or 11, based on longitudinal studies
• Transmission:
  • Skin-to-skin contact (does not require penetration Penetration X-rays)
  • Autoinoculation Autoinoculation Molluscum Contagiosum
  • Presence of warts Warts Benign epidermal proliferations or tumors; some are viral in origin. Female Genitourinary Examination increases the risk of HPV HPV Human papillomavirus (HPV) is a nonenveloped, circular, double-stranded DNA virus belonging to the Papillomaviridae family. Humans are the only reservoir, and transmission occurs through close skin-to-skin or sexual contact. Human papillomaviruses infect basal epithelial cells and can affect cell-regulatory proteins to result in cell proliferation. Papillomavirus (HPV) transmission (due to increased viral load Viral load The quantity of measurable virus in a body fluid. Change in viral load, measured in plasma, is sometimes used as a surrogate marker in disease progression. HIV Infection and AIDS)
    • Transmission is possible even in the absence of warts Warts Benign epidermal proliferations or tumors; some are viral in origin. Female Genitourinary Examination.
    • ⅔ of patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship who have intercourse with someone with CA CA Condylomata acuminata are a clinical manifestation of genital HPV infection. Condylomata acuminata are described as raised, pearly, flesh-colored, papular, cauliflower-like lesions seen in the anogenital region that may cause itching, pain, or bleeding. Condylomata Acuminata (Genital Warts) develop CA CA Condylomata acuminata are a clinical manifestation of genital HPV infection. Condylomata acuminata are described as raised, pearly, flesh-colored, papular, cauliflower-like lesions seen in the anogenital region that may cause itching, pain, or bleeding. Condylomata Acuminata (Genital Warts).
• Risk factors for development of warts Warts Benign epidermal proliferations or tumors; some are viral in origin. Female Genitourinary Examination:
  • Immunosuppression:
    • Diabetes Diabetes Diabetes mellitus (DM) is a metabolic disease characterized by hyperglycemia and dysfunction of the regulation of glucose metabolism by insulin. Type 1 DM is diagnosed mostly in children and young adults as the result of autoimmune destruction of β cells in the pancreas and the resulting lack of insulin. Type 2 DM has a significant association with obesity and is characterized by insulin resistance. Diabetes Mellitus
    • HIV HIV Anti-HIV Drugs
    • Immunosuppressive therapy
  • Multiple partners
  • History of STI STI Sexually transmitted infections (STIs) are infections that spread either by vaginal intercourse, anal sex, or oral sex. Symptoms and signs may include vaginal discharge, penile discharge, dysuria, skin lesions (e.g., warts, ulcers) on or around the genitals, and pelvic pain. Some infections can lead to infertility and chronic debilitating disease. Sexually Transmitted Infections (STIs) (especially chlamydia Chlamydia Chlamydiae are obligate intracellular gram-negative bacteria. They lack a peptidoglycan layer and are best visualized using Giemsa stain. The family of Chlamydiaceae comprises 3 pathogens that can infect humans: Chlamydia trachomatis, Chlamydia psittaci, and Chlamydia pneumoniae. Chlamydia and gonorrhea Gonorrhea Gonorrhea is a sexually transmitted infection (STI) caused by the gram-negative bacteria Neisseria gonorrhoeae (N. gonorrhoeae). Gonorrhea may be asymptomatic but commonly manifests as cervicitis or urethritis with less common presentations such as proctitis, conjunctivitis, or pharyngitis. Gonorrhea)
  • Young coital age
  • Smoking Smoking Willful or deliberate act of inhaling and exhaling smoke from burning substances or agents held by hand. Interstitial Lung Diseases

Pathophysiology^[3,4,7,12]

Infection to resolution:

• HPV HPV Human papillomavirus (HPV) is a nonenveloped, circular, double-stranded DNA virus belonging to the Papillomaviridae family. Humans are the only reservoir, and transmission occurs through close skin-to-skin or sexual contact. Human papillomaviruses infect basal epithelial cells and can affect cell-regulatory proteins to result in cell proliferation. Papillomavirus (HPV) enters through break in epithelium Epithelium The epithelium is a complex of specialized cellular organizations arranged into sheets and lining cavities and covering the surfaces of the body. The cells exhibit polarity, having an apical and a basal pole. Structures important for the epithelial integrity and function involve the basement membrane, the semipermeable sheet on which the cells rest, and interdigitations, as well as cellular junctions. Surface Epithelium: Histology.
• HPV HPV Human papillomavirus (HPV) is a nonenveloped, circular, double-stranded DNA virus belonging to the Papillomaviridae family. Humans are the only reservoir, and transmission occurs through close skin-to-skin or sexual contact. Human papillomaviruses infect basal epithelial cells and can affect cell-regulatory proteins to result in cell proliferation. Papillomavirus (HPV) infects nucleus Nucleus Within a eukaryotic cell, a membrane-limited body which contains chromosomes and one or more nucleoli (cell nucleolus). The nuclear membrane consists of a double unit-type membrane which is perforated by a number of pores; the outermost membrane is continuous with the endoplasmic reticulum. A cell may contain more than one nucleus. The Cell: Organelles of differentiated squamous epithelial cells.
• Incubation Incubation The amount time between exposure to an infectious agent and becoming symptomatic. Rabies Virus period (i.e., time from infection to development of warts Warts Benign epidermal proliferations or tumors; some are viral in origin. Female Genitourinary Examination):
  • 1 month to 2 years
  • Median: 6–10 months^[7]
• Basal cells replicate and rise to epidermal surface (3–4 months to form wart).
• Skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Skin: Structure and Functions cells shed, with viral particles becoming transmissible.
• Healthy individuals can clear infection over months to years.
  • Median time to clearance:^[7]
    • Women: 9.4 months
    • Men: 7.5 months
  • One study showed that (within the 1st 12 months after infection):^[7]
    • Warts Warts Benign epidermal proliferations or tumors; some are viral in origin. Female Genitourinary Examination cleared in 80% of women without HIV HIV Anti-HIV Drugs/ AIDs AIDS Chronic HIV infection and depletion of CD4 cells eventually results in acquired immunodeficiency syndrome (AIDS), which can be diagnosed by the presence of certain opportunistic diseases called AIDS-defining conditions. These conditions include a wide spectrum of bacterial, viral, fungal, and parasitic infections as well as several malignancies and generalized conditions. HIV Infection and AIDS.
    • Warts Warts Benign epidermal proliferations or tumors; some are viral in origin. Female Genitourinary Examination cleared in 60% of women living with HIV HIV Anti-HIV Drugs/ AIDs AIDS Chronic HIV infection and depletion of CD4 cells eventually results in acquired immunodeficiency syndrome (AIDS), which can be diagnosed by the presence of certain opportunistic diseases called AIDS-defining conditions. These conditions include a wide spectrum of bacterial, viral, fungal, and parasitic infections as well as several malignancies and generalized conditions. HIV Infection and AIDS.
• Disease recurrence is possible if the infection is not fully cleared.

Histopathology^[4]

• Proliferation in all epithelial layers:
  • Hyperkeratosis Hyperkeratosis Ichthyosis Vulgaris
  • Acanthosis
  • Parakeratosis Parakeratosis Persistence of the nuclei of the keratinocytes into the stratum corneum of the skin. This is a normal state only in the epithelium of true mucous membranes in the mouth and vagina. Actinic Keratosis
• Perinuclear cytoplasmic vacuolization Cytoplasmic vacuolization Norovirus and nuclear enlargement

Clinical Presentation

Patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship are often asymptomatic, presenting only for the appearance of lesions. The diagnosis of HPV HPV Human papillomavirus (HPV) is a nonenveloped, circular, double-stranded DNA virus belonging to the Papillomaviridae family. Humans are the only reservoir, and transmission occurs through close skin-to-skin or sexual contact. Human papillomaviruses infect basal epithelial cells and can affect cell-regulatory proteins to result in cell proliferation. Papillomavirus (HPV) may cause significant psychosocial distress, given the associated stigma.

Lesion characteristics^[2,3]

• Exophytic Exophytic Retinoblastoma (cauliflower-like)
• May be broad-based or pedunculated (on a stalk)
• Flesh-colored or darker
• < 5 mm; may appear larger when grouped together
• Often asymptomatic
• If symptomatic:
  • Pruritus Pruritus An intense itching sensation that produces the urge to rub or scratch the skin to obtain relief. Atopic Dermatitis (Eczema)
  • Discomfort
  • Rarely bleeding or local erosion Erosion Partial-thickness loss of the epidermis Generalized and Localized Rashes

Location^[2–4]

• One or multiple warts Warts Benign epidermal proliferations or tumors; some are viral in origin. Female Genitourinary Examination
• Women:
  • Labia majora Labia majora Vagina, Vulva, and Pelvic Floor: Anatomy
  • Vagina Vagina The vagina is the female genital canal, extending from the vulva externally to the cervix uteri internally. The structures have sexual, reproductive, and urinary functions and a rich blood supply, mainly arising from the internal iliac artery. Vagina, Vulva, and Pelvic Floor: Anatomy
  • Cervix Cervix The uterus, cervix, and fallopian tubes are part of the internal female reproductive system. The most inferior portion of the uterus is the cervix, which connects the uterine cavity to the vagina. Externally, the cervix is lined by stratified squamous cells; however, the cervical canal is lined by columnar epithelium. Uterus, Cervix, and Fallopian Tubes: Anatomy
  • Anus/anal canal
• Men:
  • Glans penis Glans Penis Penis: Anatomy
  • Scrotum Scrotum A cutaneous pouch of skin containing the testicles and spermatic cords. Testicles: Anatomy
  • Urethra Urethra A tube that transports urine from the urinary bladder to the outside of the body in both the sexes. It also has a reproductive function in the male by providing a passage for sperm. Urinary Tract: Anatomy
  • Anus/anal canal

Diagnosis

• Clinical diagnosis:
  • Characteristic appearance
  • Appropriate patient population
• Biopsy Biopsy Removal and pathologic examination of specimens from the living body. Ewing Sarcoma performed:
  • To confirm etiology
  • If dysplasia suspected
• Lesions in inguinal region Inguinal region Anterior Abdominal Wall: Anatomy: Panel to rule out other accompanying STI STI Sexually transmitted infections (STIs) are infections that spread either by vaginal intercourse, anal sex, or oral sex. Symptoms and signs may include vaginal discharge, penile discharge, dysuria, skin lesions (e.g., warts, ulcers) on or around the genitals, and pelvic pain. Some infections can lead to infertility and chronic debilitating disease. Sexually Transmitted Infections (STIs)

Management and Complications

The following information is based on US and UK recommendations and guidelines. Also refer to your local management guidelines.

Prevention

Vaccination Vaccination Vaccination is the administration of a substance to induce the immune system to develop protection against a disease. Unlike passive immunization, which involves the administration of pre-performed antibodies, active immunization constitutes the administration of a vaccine to stimulate the body to produce its own antibodies. Vaccination:

• > 99% efficacy when vaccine Vaccine Suspensions of killed or attenuated microorganisms (bacteria, viruses, fungi, protozoa), antigenic proteins, synthetic constructs, or other bio-molecular derivatives, administered for the prevention, amelioration, or treatment of infectious and other diseases. Vaccination is received prior to exposure^[10]
• Several options exist, protecting against different numbers of HPV HPV Human papillomavirus (HPV) is a nonenveloped, circular, double-stranded DNA virus belonging to the Papillomaviridae family. Humans are the only reservoir, and transmission occurs through close skin-to-skin or sexual contact. Human papillomaviruses infect basal epithelial cells and can affect cell-regulatory proteins to result in cell proliferation. Papillomavirus (HPV) strains:^[2]
  • Bivalent: HPV 16 HPV 16 A type of alphapapillomavirus usually associated with genital warts; and laryngeal neoplasms. Papillomavirus (HPV) and 18
  • Quadrivalent: HPV 6 HPV 6 A type of alphapapillomavirus usually associated with genital warts; and laryngeal neoplasms. Papillomavirus (HPV), 11, 16, and 18
  • 9-valent (currently the only vaccine Vaccine Suspensions of killed or attenuated microorganisms (bacteria, viruses, fungi, protozoa), antigenic proteins, synthetic constructs, or other bio-molecular derivatives, administered for the prevention, amelioration, or treatment of infectious and other diseases. Vaccination available in the US): HPV 6 HPV 6 A type of alphapapillomavirus usually associated with genital warts; and laryngeal neoplasms. Papillomavirus (HPV), 11, 16, 18, 31, 33, 45, 52, and 58
• Requires 2 doses, 6 months apart (may be given up to 24 months apart)
• Vaccination Vaccination Vaccination is the administration of a substance to induce the immune system to develop protection against a disease. Unlike passive immunization, which involves the administration of pre-performed antibodies, active immunization constitutes the administration of a vaccine to stimulate the body to produce its own antibodies. Vaccination strategy varies by country:^[3]
  • Most beneficial prior to 1st sexual contact, so typically recommended in children/young adolescents, often starting around ages 10–12 years
  • Typically recommended for both boys and girls
• In the US, per the Centers for Disease Control and Prevention (CDC) and the American College of Obstetricians and Gynecologists (ACOG):^[10,15]
  • HPV HPV Human papillomavirus (HPV) is a nonenveloped, circular, double-stranded DNA virus belonging to the Papillomaviridae family. Humans are the only reservoir, and transmission occurs through close skin-to-skin or sexual contact. Human papillomaviruses infect basal epithelial cells and can affect cell-regulatory proteins to result in cell proliferation. Papillomavirus (HPV) vaccination Vaccination Vaccination is the administration of a substance to induce the immune system to develop protection against a disease. Unlike passive immunization, which involves the administration of pre-performed antibodies, active immunization constitutes the administration of a vaccine to stimulate the body to produce its own antibodies. Vaccination is licensed for women and men up through age 45.
  • HPV HPV Human papillomavirus (HPV) is a nonenveloped, circular, double-stranded DNA virus belonging to the Papillomaviridae family. Humans are the only reservoir, and transmission occurs through close skin-to-skin or sexual contact. Human papillomaviruses infect basal epithelial cells and can affect cell-regulatory proteins to result in cell proliferation. Papillomavirus (HPV) vaccination Vaccination Vaccination is the administration of a substance to induce the immune system to develop protection against a disease. Unlike passive immunization, which involves the administration of pre-performed antibodies, active immunization constitutes the administration of a vaccine to stimulate the body to produce its own antibodies. Vaccination with the 9-valent vaccine Vaccine Suspensions of killed or attenuated microorganisms (bacteria, viruses, fungi, protozoa), antigenic proteins, synthetic constructs, or other bio-molecular derivatives, administered for the prevention, amelioration, or treatment of infectious and other diseases. Vaccination starting at ages 11–12 years
  • Vaccination Vaccination Vaccination is the administration of a substance to induce the immune system to develop protection against a disease. Unlike passive immunization, which involves the administration of pre-performed antibodies, active immunization constitutes the administration of a vaccine to stimulate the body to produce its own antibodies. Vaccination in all people ≤ 26 years of age, if not yet vaccinated
  • Joint decision-making between patient and provider for unvaccinated people ages 27–45
• In the UK, the National Health Service (NHS) immunization schedule recommends giving the 1st dose to children 12–13 years of age.^[14]

Other protective measures:

• Condoms Condoms A sheath that is worn over the penis during sexual behavior in order to prevent pregnancy or spread of sexually transmitted disease. Nonhormonal Contraception (consistent use can decrease risk of acquisition by 30%–60%)^[2,15]
• Being in a mutually monogamous relationship^[15]
• Smoking Smoking Willful or deliberate act of inhaling and exhaling smoke from burning substances or agents held by hand. Interstitial Lung Diseases cessation (can decrease risk of acquisition)^[3]

General management^[1-3]

Spontaneous and complete resolution can take up to 24 months.

• Goals of therapy:
  • Remove warts Warts Benign epidermal proliferations or tumors; some are viral in origin. Female Genitourinary Examination.
  • Improve symptoms (including psychosocial distress, which can be significant).
• Treatment options (failure and relapse Relapse Relapsing Fever rates are high for all options):
  • Observation:
    • Warts Warts Benign epidermal proliferations or tumors; some are viral in origin. Female Genitourinary Examination often spontaneously resolve within 12 months.
    • Risk of transmission is likely higher.
  • Provider-administered surgical or destructive therapies
  • Patient-applied topical therapies

Provider-administered therapies

Note: These therapies require specialized training. Referral to specialists (e.g., gynecologist, urologist) may be appropriate.

Cryotherapy Cryotherapy A form of therapy consisting in the local or general use of cold. The selective destruction of tissue by extreme cold or freezing is cryosurgery. Chondrosarcoma:^[1–3]

• Options:
  • Liquid nitrogen Liquid Nitrogen Molluscum Contagiosum (spray device)
  • Cryoprobe (a closed system with a probe Probe A device placed on the patient’s body to visualize a target Ultrasound (Sonography) using nitrous oxide Nitrous oxide Nitrogen oxide (N2O). A colorless, odorless gas that is used as an anesthetic and analgesic. High concentrations cause a narcotic effect and may replace oxygen, causing death by asphyxia. Inhaled Anesthetics or CO₂)
• Cause thermal cytolysis
• Treatment is applied until a “halo” of freezing is present a few millimeters around the lesion (typically 15–30 seconds).
• Can administer 1–3 freezes to each lesion at each visit
• May be repeated weekly (consider alternatives after 4 weeks)
• Safe in pregnancy Pregnancy The status during which female mammals carry their developing young (embryos or fetuses) in utero before birth, beginning from fertilization to birth. Pregnancy: Diagnosis, Physiology, and Care
• Clearance rate: 45%–85%^[3]

80%–90% acid solutions:^[1–3]

• Solutions:
  • Trichloroacetic acid (TCA, solution typically used)
  • Bichloroacetic acid (BCA)
• Highly caustic agents resulting in cellular necrosis Necrosis The death of cells in an organ or tissue due to disease, injury or failure of the blood supply. Ischemic Cell Damage through chemical coagulation of proteins Proteins Linear polypeptides that are synthesized on ribosomes and may be further modified, crosslinked, cleaved, or assembled into complex proteins with several subunits. The specific sequence of amino acids determines the shape the polypeptide will take, during protein folding, and the function of the protein. Energy Homeostasis
• Applied directly to warts Warts Benign epidermal proliferations or tumors; some are viral in origin. Female Genitourinary Examination, usually once weekly, with a wooden or cotton-tipped applicator
• TCA has low viscosity → spreads easily to surrounding tissue (which can cause damage)
• Protect surrounding area with petroleum jelly.
• In cases of inadvertent exposure to surrounding tissue (or intense pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways):
  • A neutralizing agent (e.g., 5% sodium Sodium A member of the alkali group of metals. It has the atomic symbol na, atomic number 11, and atomic weight 23. Hyponatremia bicarbonate Bicarbonate Inorganic salts that contain the -HCO3 radical. They are an important factor in determining the ph of the blood and the concentration of bicarbonate ions is regulated by the kidney. Levels in the blood are an index of the alkali reserve or buffering capacity. Electrolytes) can be applied.
  • Wash with liquid soap.
• Clearance rate: 55%–95%^[3]

Surgical removal:^[1–3]

• Options:
  • Scissor excision
  • Shave excision
  • Curettage Curettage A scraping, usually of the interior of a cavity or tract, for removal of new growth or other abnormal tissue, or to obtain material for tissue diagnosis. It is performed with a curet (curette), a spoon-shaped instrument designed for that purpose. Benign Bone Tumors
  • Laser
  • Electrosurgery/ electrocautery Electrocautery Surgical Instruments and Sutures
• Typically, can be done under local anesthesia Anesthesia A state characterized by loss of feeling or sensation. This depression of nerve function is usually the result of pharmacologic action and is induced to allow performance of surgery or other painful procedures. Anesthesiology: History and Basic Concepts (e.g., 1%–2% subcutaneous lidocaine Lidocaine A local anesthetic and cardiac depressant used as an antiarrhythmic agent. Its actions are more intense and its effects more prolonged than those of procaine but its duration of action is shorter than that of bupivacaine or prilocaine. Local Anesthetics)
• Electrosurgery, electrocautery Electrocautery Surgical Instruments and Sutures, and laser treatments require N95 masks to prevent people in the treatment room from inhaling infectious HPV HPV Human papillomavirus (HPV) is a nonenveloped, circular, double-stranded DNA virus belonging to the Papillomaviridae family. Humans are the only reservoir, and transmission occurs through close skin-to-skin or sexual contact. Human papillomaviruses infect basal epithelial cells and can affect cell-regulatory proteins to result in cell proliferation. Papillomavirus (HPV) particles in the smoke.
• Clearance rate: 95%–100%^[3]

Patient-applied therapies^[1–3]

Imiquimod Imiquimod A topically-applied aminoquinoline immune modulator that induces interferon production. It is used in the treatment of external genital and perianal warts, superficial carcinoma, basal cell; and actinic keratosis. Hypertrophic and Keloid Scars 3.75% or 5% cream:^[1–3]

• An immune modifier that stimulates production of interferon and other cytokines Cytokines Non-antibody proteins secreted by inflammatory leukocytes and some non-leukocytic cells, that act as intercellular mediators. They differ from classical hormones in that they are produced by a number of tissue or cell types rather than by specialized glands. They generally act locally in a paracrine or autocrine rather than endocrine manner. Adaptive Immune Response
• 3.57% cream: Apply to lesions once daily at bedtime, every night, for up to 8 weeks.
• 5% cream: Apply to lesions once daily at bedtime, 3 times per week, for up to 16 weeks.
• Wash treatment areas with soap and water 6‒10 hours after applying cream
• Notes:
  • Imiquimod Imiquimod A topically-applied aminoquinoline immune modulator that induces interferon production. It is used in the treatment of external genital and perianal warts, superficial carcinoma, basal cell; and actinic keratosis. Hypertrophic and Keloid Scars can weaken latex condoms Condoms A sheath that is worn over the penis during sexual behavior in order to prevent pregnancy or spread of sexually transmitted disease. Nonhormonal Contraception.
  • May exacerbate inflammatory skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Skin: Structure and Functions conditions
  • Avoid in pregnancy Pregnancy The status during which female mammals carry their developing young (embryos or fetuses) in utero before birth, beginning from fertilization to birth. Pregnancy: Diagnosis, Physiology, and Care.
• Clearance rate: 35%–75%

Podophyllotoxin Podophyllotoxin A lignan (lignans) found in podophyllin resin from the roots of podophyllum plants. It is a potent spindle poison, toxic if taken internally, and has been used as a cathartic. It is very irritating to skin and mucous membranes, has keratolytic actions, has been used to treat warts and keratoses, and may have antineoplastic properties, as do some of its congeners and derivatives. Molluscum Contagiosum (podofilox):^[1–3]

• An antimitotic drug causing wart necrosis Necrosis The death of cells in an organ or tissue due to disease, injury or failure of the blood supply. Ischemic Cell Damage
• Preparations:
  • 0.5% solution (apply with a cotton swab)
  • 0.5% gel (apply with fingers)
  • 0.15% cream (apply with fingers)
• Regimen:
  • Apply to lesions twice daily for 3 days, then rest for 4 days 
  • Repeat for 4–5 weeks.
• Notes:
  • Total treatment area should not exceed 10 cm³.
  • Avoid in pregnancy Pregnancy The status during which female mammals carry their developing young (embryos or fetuses) in utero before birth, beginning from fertilization to birth. Pregnancy: Diagnosis, Physiology, and Care.
• Clearance rate: approximately 36%–83%

Sinecatechins (Catephen^Ⓡ, Veregen^Ⓡ) 10%–15% ointment:^[1–3]

• Apply a 0.5-cm strand of ointment to each wart, using a finger to create a thin layer over warts Warts Benign epidermal proliferations or tumors; some are viral in origin. Female Genitourinary Examination .
• Use 3 times daily for up to 16 weeks.
• Do not wash off after use.
• Sexual contact should be avoided while ointment is on the skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Skin: Structure and Functions.
• Clearance rate: approximately 50%

After application of any treatment:

• Wash hands.
• Allow treatment to fully dry.
• Avoid sexual contact shortly after application (may cause irritation in partner).

Common adverse reactions:

• Tenderness/irritation
• Erythema Erythema Redness of the skin produced by congestion of the capillaries. This condition may result from a variety of disease processes. Chalazion
• Ulceration Ulceration Corneal Abrasions, Erosion, and Ulcers/ erosion Erosion Partial-thickness loss of the epidermis Generalized and Localized Rashes (discontinue treatment)

Choosing a treatment option^[1–3,13]

Factors to consider when deciding on treatment options:

• Wart size, number, and anatomic site:
  • Vaginal, cervical, intra-meatal (urethral), and intra-anal warts Warts Benign epidermal proliferations or tumors; some are viral in origin. Female Genitourinary Examination require either cryotherapy Cryotherapy A form of therapy consisting in the local or general use of cold. The selective destruction of tissue by extreme cold or freezing is cryosurgery. Chondrosarcoma, TCA, or surgical treatment.
  • Cervical warts Warts Benign epidermal proliferations or tumors; some are viral in origin. Female Genitourinary Examination require referral to gynecology.
  • Intra-meatal (urethral) warts Warts Benign epidermal proliferations or tumors; some are viral in origin. Female Genitourinary Examination require surgical treatment if the base of the lesion is not clearly visible.
  • Larger wart burdens (especially > 10 cm³) should be treated surgically
• Patient preference
• Cost and convenience of treatments
• Adverse effects
• An article proposed that in the UK, the most cost-effective treatment strategy used:^[13]
  • Podophyllotoxin Podophyllotoxin A lignan (lignans) found in podophyllin resin from the roots of podophyllum plants. It is a potent spindle poison, toxic if taken internally, and has been used as a cathartic. It is very irritating to skin and mucous membranes, has keratolytic actions, has been used to treat warts and keratoses, and may have antineoplastic properties, as do some of its congeners and derivatives. Molluscum Contagiosum 0.5% solution as 1st-line therapy
  • Followed by CO₂ laser therapy Laser Therapy The use of photothermal effects of lasers to coagulate, incise, vaporize, resect, dissect, or resurface tissue. Glaucoma or surgery as 2nd-line therapy

Complications^[1–3]

• After treatment:
  • Hypopigmentation Hypopigmentation A condition caused by a deficiency or a loss of melanin pigmentation in the epidermis, also known as hypomelanosis. Hypopigmentation can be localized or generalized, and may result from genetic defects, trauma, inflammation, or infections. Malassezia Fungi or scarring Scarring Inflammation
  • Recurrence
• Psychosocial impact
• Coinfection with high-risk types of HPV HPV Human papillomavirus (HPV) is a nonenveloped, circular, double-stranded DNA virus belonging to the Papillomaviridae family. Humans are the only reservoir, and transmission occurs through close skin-to-skin or sexual contact. Human papillomaviruses infect basal epithelial cells and can affect cell-regulatory proteins to result in cell proliferation. Papillomavirus (HPV) may result in development of carcinoma.
  • Ensure that cervical cancer Cervical cancer Cervical cancer, or invasive cervical carcinoma (ICC), is the 3rd most common cancer in women in the world, with > 50% of the cases being fatal. In the United States, ICC is the 13th most common cancer and the cause of < 3% of all cancer deaths due to the slow progression of precursor lesions and, more importantly, effective cancer screening. Cervical Cancer screening Screening Preoperative Care is up to date (e.g., Pap smear Pap smear Cytological preparation of cells collected from a mucosal surface and stained with Papanicolaou stain. Cervical Cancer Screening and cervical HPV testing HPV testing Cervical Cancer Screening).

Differential Diagnosis

• Condylomata lata Condylomata Lata Syphilis (CL): second stage of syphilis Syphilis Syphilis is a bacterial infection caused by the spirochete Treponema pallidum pallidum (T. p. pallidum), which is usually spread through sexual contact. Syphilis has 4 clinical stages: primary, secondary, latent, and tertiary. Syphilis ( STI STI Sexually transmitted infections (STIs) are infections that spread either by vaginal intercourse, anal sex, or oral sex. Symptoms and signs may include vaginal discharge, penile discharge, dysuria, skin lesions (e.g., warts, ulcers) on or around the genitals, and pelvic pain. Some infections can lead to infertility and chronic debilitating disease. Sexually Transmitted Infections (STIs) caused by Treponema pallidum Treponema pallidum The causative agent of venereal and non-venereal syphilis as well as yaws. Treponema): Condylomata lata Condylomata Lata Syphilis present with wartlike lesions that are similar to those of HPV HPV Human papillomavirus (HPV) is a nonenveloped, circular, double-stranded DNA virus belonging to the Papillomaviridae family. Humans are the only reservoir, and transmission occurs through close skin-to-skin or sexual contact. Human papillomaviruses infect basal epithelial cells and can affect cell-regulatory proteins to result in cell proliferation. Papillomavirus (HPV). These lesions are confined to areas with moisture and are usually gray-white in color. The patient may have a history of a chancre Chancre The primary sore of syphilis, a painless indurated, eroded papule, occurring at the site of entry of the infection. Syphilis. Workup must include an STD panel. Syphilis Syphilis Syphilis is a bacterial infection caused by the spirochete Treponema pallidum pallidum (T. p. pallidum), which is usually spread through sexual contact. Syphilis has 4 clinical stages: primary, secondary, latent, and tertiary. Syphilis is diagnosed using a combination of serologic treponemal and nontreponemal tests. Treatment is with penicillin Penicillin Rheumatic Fever.
• Seborrheic keratosis Seborrheic keratosis Seborrheic keratosis (SK) is the most common benign epithelial cutaneous neoplasm. The condition consists of immature keratinocytes. Seborrheic keratosis is the most common benign skin tumor in middle-aged and elderly adults and presents as a sharply demarcated, exophytic, skin lesion that may be tan or black and has a “stuck-on” appearance. Seborrheic Keratosis ( SK SK Seborrheic keratosis (sk) is the most common benign epithelial cutaneous neoplasm. The condition consists of immature keratinocytes. Seborrheic keratosis is the most common benign skin tumor in middle-aged and elderly adults and presents as a sharply demarcated, exophytic, skin lesion that may be tan or black and has a “stuck-on” appearance. Seborrheic Keratosis): the most common benign Benign Fibroadenoma epithelial cutaneous neoplasm, consisting of immature keratinocytes Keratinocytes Epidermal cells which synthesize keratin and undergo characteristic changes as they move upward from the basal layers of the epidermis to the cornified (horny) layer of the skin. Successive stages of differentiation of the keratinocytes forming the epidermal layers are basal cell, spinous or prickle cell, and the granular cell. Skin: Structure and Functions. Seborrheic keratosis Seborrheic keratosis Seborrheic keratosis (SK) is the most common benign epithelial cutaneous neoplasm. The condition consists of immature keratinocytes. Seborrheic keratosis is the most common benign skin tumor in middle-aged and elderly adults and presents as a sharply demarcated, exophytic, skin lesion that may be tan or black and has a “stuck-on” appearance. Seborrheic Keratosis presents as a sharply demarcated, exophytic Exophytic Retinoblastoma, skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Skin: Structure and Functions lesion that may be tan or black and has a “stuck-on” appearance similar to the genital warts Warts Benign epidermal proliferations or tumors; some are viral in origin. Female Genitourinary Examination caused by HPV HPV Human papillomavirus (HPV) is a nonenveloped, circular, double-stranded DNA virus belonging to the Papillomaviridae family. Humans are the only reservoir, and transmission occurs through close skin-to-skin or sexual contact. Human papillomaviruses infect basal epithelial cells and can affect cell-regulatory proteins to result in cell proliferation. Papillomavirus (HPV). This condition is usually present on limbs or face. Management is similar to cryotherapy Cryotherapy A form of therapy consisting in the local or general use of cold. The selective destruction of tissue by extreme cold or freezing is cryosurgery. Chondrosarcoma.
• Molluscum contagiosum: presents with lesions that are grouped, flesh-colored, firm, dome-shaped papules with central umbilication. Caused by the molluscum contagiosum virus Molluscum contagiosum virus A species of molluscipoxvirus causing skin lesions in humans. It is transmitted by direct contact or from non-living reservoirs (fomites), such as books or clothing. Molluscum Contagiosum, which is a member of the poxvirus family. This condition is usually seen in children, though it can be seen in adults. Since it is transmitted via direct skin-to-skin contact, The condition is typically diagnosed based on clinical appearance, but it can be definitively differentiated from genital warts Warts Benign epidermal proliferations or tumors; some are viral in origin. Female Genitourinary Examination via biopsy Biopsy Removal and pathologic examination of specimens from the living body. Ewing Sarcoma; molluscum contagiosum Molluscum contagiosum Molluscum contagiosum is a viral infection limited to the epidermis and is common in children below 5 years of age. Lesions appear as grouped, flesh-colored, dome-shaped papules with central umbilication. Molluscum Contagiosum specimens will show eosinophilic cytoplasmic inclusions known as Henderson-Paterson bodies. Management is supportive; may consider cryotherapy Cryotherapy A form of therapy consisting in the local or general use of cold. The selective destruction of tissue by extreme cold or freezing is cryosurgery. Chondrosarcoma for cosmesis.
• Fordyce spots:^[12] 1‒3 mm benign Benign Fibroadenoma, noninfectious lesions that present as multiple small white-yellow papules and are usually asymptomatic (though may be slightly pruritic). These spots are clusters of ectopic sebaceous glands (not associated with a hair follicle Hair follicle A tube-like invagination of the epidermis from which the hair shaft develops and into which sebaceous glands open. The hair follicle is lined by a cellular inner and outer root sheath of epidermal origin and is invested with a fibrous sheath derived from the dermis. Follicles of very long hairs extend into the subcutaneous layer of tissue under the skin. Cowden Syndrome) that open directly to the surface and can be seen on the penis Penis The penis is the male organ of copulation and micturition. The organ is composed of a root, body, and glans. The root is attached to the pubic bone by the crura penis. The body consists of the 2 parallel corpora cavernosa and the corpus spongiosum. The glans is ensheathed by the prepuce or foreskin. Penis: Anatomy, on the testicles Testicles The testicles, also known as the testes or the male gonads, are a pair of egg-shaped glands suspended within the scrotum. The testicles have multiple layers: an outer tunica vaginalis, an intermediate tunica albuginea, and an innermost tunica vasculosa. The testicles are composed of testicular lobules and seminiferous tubules. Testicles: Anatomy, around the labia, and on the lips Lips The lips are the soft and movable most external parts of the oral cavity. The blood supply of the lips originates from the external carotid artery, and the innervation is through cranial nerves. Lips and Tongue: Anatomy and in the mouth.