Human Papillomavirus
Cheryl A. Glass and Leslie B. Norman
Definition
A.The human papillomavirus (HPV) is an sexually transmitted infection (STI). Condylomata acuminata, genital warts, and venereal warts are other names for HPV.
Incidence
A.HPV is the most common STI in the United States.
B.In 2013 to 2014, among adults ages 15 to 59 years, about 45% of men and 40% of women had genital HPV infections. About 25% of men and 20% of women had high-risk genital HPV infection. The prevalence of any type of oral HPV infection among adults ages 18 to 69 in 2011 to 2014 was about 7% and the prevalence of high-risk oral HPV infections was 4%.
C.Most sexually active persons become infected with HPV at least once in their lifetime. Condoms provide some protection against HPV transmission, but contact with genital lesions not covered by the condom can result in infection. Patients with anogenital warts may be at risk for other STIs.
TABLE 18.1 Pharmacological Treatment of Herpes in Pregnancy
TABLE 18.1 Pharmacological Treatment of Herpes in Pregnancy
bid, twice a day; tid, three times a day.
D.Prevention:
1.Three vaccines are approved by the Food and Drug Administration (FDA) to prevent HPV infection: Gardasil, Gardasil 9, and Cervarix. All three vaccines prevent infections with HPV types 16 and 18 that cause about 70% of cervical cancers and an even higher percentage of some other HPV-associated cancers:
a.Gardasil prevents infection with HPV types 6 and 11, which cause 90% of genital warts.
b.Gardasil 9 prevents infections with the same four HPV types plus five additional high-risk types (31, 33, 45, 52, and 58):
i.Gardasil is approved for use in males ages 9 to 26 years.
ii.Gardasil 9 is approved for use in males ages 9 to 15 years.
iii.Carvarix is approved for females ages 9 to 25 years.
2.As of 2016, the Centers for Disease Control and Prevention (CDC) recommend the HPV vaccine:
a.Routinely given in two doses for males and females from age 11 years to before the 15th birthday.
b.The vaccination can be started at age 9 years.
c.Three doses of HPV vaccine are recommended for people starting the vaccination series on or after their 15th birthday and other people with certain immunocompromising conditions.
d.Vaccinate through age 26 years for females.
e.Vaccinate through age 21 for males. Males 22 to 26 years may be vaccinated.
Pathogenesis
A.The HPV, a slow-growing DNA virus of the papovavirus family, is the causative organism. The usual incubation period for clinical warts is 3 weeks to 8 months. Over 100 strains of the virus have been identified. At least 40 of the HPV types can infect the genital area.
B.HPV types 6 and 11 are most associated with genital warts and recurrent respiratory papillomatosis.
C.Types 16, 18, 31, 33, and 35 are high risk and are associated with cervical, penile, vulvar, vaginal, and oropharyngeal neoplasia and precancers.
D.Ninety percent of anogenital warts are caused by nononcogenic HPV types 6 or 11. HPV types 16, 18, 31, and 35 are occasionally found in anogenital warts usually as coinfections with HPV 6 or 11 and can be associated with foci of high-grade squamous intraepithelial lesions (HSIL), particularly in persons who have HIV. Anogenital warts, HPV types 6 and 11 have been associated with conjunctival, nasal, oral, and laryngeal warts.
E.HPV also might be transmitted during genital-to-genital contact without penetration and oral sex.
F.Warts may appear as early as 1 to 2 months after exposure, but most infections remain subclinical. The first recognition of a lesion may represent a relapse rather than a first episode.
Predisposing Factors
A.Early first coitus.
B.Multiple sexual partners.
C.Individual and partner’s history of STIs.
D.Gay, bisexual, and other men having sex with men (MSM).
E.Factors contributing to increase of STIs in older adults:
1.Undereducated: Older adults are less likely to perceive themselves at risk. Safe sex and STI prevention education came in the 1980s dealing with the HIV crisis during the time older adults were married and middle-aged. Seniors may feel sex education is directed to youth and pregnancy prevention.
2.Medications for erectile dysfunction have contributed to more men being able to engage in sexual activity throughout their older years.
3.Online dating lowers the chance that partners know the background and sexual history of people they date.
4.Women are postmenopausal and do not worry about getting pregnant with new partners.
Common Complaints
A.Painless genital bumps
or warts.
B.Pruritus.
C.Bleeding during or after coitus.
D.Malodorous vaginal discharge.
E.Dysuria.
Other Signs and Symptoms
A.Wart-like growths on the genital area, which are elevated and rough or flat and smooth.
B.Lesions occurring singly or in clusters, from less than 1 mm to cauliflower-like aggregates.
C.Anogenital warts are flat, papular, or pedunculated growths on the genital mucosa.
D.Papillomas that are pale pink in color.
Subjective Data
A.Elicit history of onset of symptoms, location, frequency, duration, and associated symptomatology.
B.Question the patient about the history of other STIs, sexual behaviors, recent change in sexual partner, and partner’s history of STIs.
C.Men with external condylomata acuminata may have associated involvement of the urethra or anal canal.
D.Review any previous treatments and their outcome.
Physical Examination
A.Inspect:
1.Inspect vaginal introitus. Warts can also occur at multiple sites in the anogenital epithelium or within the anogenital tract (cervix, vagina, urethra, perineum, perianal skin, anus, and scrotum).
2.Females, speculum exam: Inspect vaginal walls and cervix for lesions.
3.Males: Inspect under the foreskin of the uncircumcised penis, and on the shaft of the circumcised penis.
4.Oral examination.
Diagnostic Tests
HPV tests are available to detect oncogenic types of HPV and are used in the context of cervical cancer screening and management or follow-up of abnormal cervical cytology or histology. HPV testing should not be used for male partners of women with HPV or women less than 25 years of age for diagnosis of genital warts. HPV testing is not a general STI test. HPV testing is not recommended for anogenital wart diagnosis, because the test results are not confirmatory and do not guide genital wart management.
A.Visual identification is adequate in most cases.
B.The routine use of applying 3% to 5% acetic acid to detect genital mucosa changes attributed to HPV infection is not recommended because the results do not influence clinical management.
C.Cytology: Pap smears are useful for screening. Pap results of koilocytosis, dyskeratosis, keratinizing atypia, atypical inflammation, and parakeratosis are all suggestive of HPV.
D.Histology: Colposcopy with directed biopsy is diagnostic for subclinical lesions, dysplasia, and malignancy.
E.Anoscopy: Refer patient to a gastroenterologist or a colorectal surgeon to examine the anal canal.
F.Indication for biopsy:
1.Patient is immunocompromised, including those infected with HIV.
2.Lesions do not respond to standard therapy.
3.Worsens during therapy.
G.DNA typing: Determination of specific strains is useful in diagnosing subclinical infections (the test is costly and false negatives occur).
Differential Diagnoses
A.HPV.
B.Condylomata latum of syphilis.
C.Molluscum contagiosum.
D.Seborrheic keratosis.
E.Pearly penile papules.
F.Fordyce spots.
G.Lichen planus.
H.Papulosquamous lichen planus of the penis.
I.Carcinoma.
Plan
A.General interventions: Make diagnosis promptly to discuss management. If left untreated, warts may resolve spontaneously within a year, remain unchanged, or increase in size or number.
B. 
See Section III: Patient Teaching Guide Human Papillomavirus (HPV)
:
1.Educate about HPV vaccines. Although HPV vaccines have been found to be safe when given to people who are already infected with HPV, the vaccines do not treat infection. They provide maximum benefit if a person receives them before he or she is sexually active.
2.Most HPV infections are self-limited and are asymptomatic or unrecognized. Counsel patients that anogenital HPV infection is common but can infect other areas including the mouth and throat.
3.Explain to the patient that therapy eliminates visible warts but does not eradicate the virus. No therapy has been shown to be effective in eradication of HPV. Ablation of warts may decrease viral load and transmissibility.
4.Advise the patient to abstain from genital contact while lesions are present.
C.Pharmaceutical therapy:
1.Treatment is directed to genital warts or pathologic precancerous lesions caused by HPV and to alleviate symptoms (pruritus, bleeding, burning, tenderness, obstruction of the vagina/anus). All therapies cause localized discomfort including itching, burning, erosions, and pain because the epithelium is disrupted.
2.Therapy is not recommended for subclinical infections (absence of exophytic warts). Subclinical genital HPV typically clears spontaneously:
a.There are two broad categories of medical therapy: those that directly destroy the wart tissue (cytodestructive) and those that work through the immune system (immune-mediated therapies).
b.In general, if the patient does not respond to initial therapy in about 3 weeks or complete clearance has not occurred by 6 to 12 weeks, it is appropriate to switch to a different treatment:
i.Some methods can only be applied in the office, while others can be self-administered by the patient at home. Podophyllotoxin (podofilox), imiquimod, sinecatechins, and topical interferon can be self-administered.
ii.Vaginal warts can only be treated with trichloroacetic acid (TCA), bichloroacetic acid (BCA), and interferons.
3.Cytodestructive therapies:
a.Podophyllum resin (podophyllin) 10% to 25% in tincture of benzoin compound applied weekly to visible warts by clinician until warts resolve:
i.No more than 0.5 mL should be applied at each treatment session and large areas should not be treated in a single application because of potential pain when the area becomes necrotic.
b.TCA and BCA are caustic acids that destroy the wart tissue via chemical coagulation of tissue proteins:
i.TCA is most commonly used and must be applied by a healthcare provider. It can be used on the vulva and vagina, and during pregnancy:
•TCA 80% to 90% solution is applied weekly to visible warts by clinician until warts resolve. If unresolved after six applications, consider other therapy. See Section II: Procedure for Trichloroacetic Acid (TCA)/Podophyllin Therapy.
•Excessive application of TCA 80% to 90% can cause extensive chemical burns of the vagina, vulva, and adjacent health tissue.
•Fluorouracil (FU) is a pyrimidine antimetabolite that interferes with DNA synthesis by blocking methylation of deoxyuridylic acid, leading to cell death.
ii.The FDA has not approved any formulation of FU for treatment of anogenital warts.
iii.FU is poorly tolerated because of burning, pain, inflammation, edema, or painful ulcerations. For these reasons, topical FU has a limited role in the primary therapy of vulvar or vaginal warts.
c.Podofilox 0.5% gel is for home treatment. It is applied to visible warts that have been identified by the healthcare provider twice daily (a.m. and p.m.) for 3 consecutive days, followed by 4 days without treatment. The cycle is repeated up to four times. Patients should contact the office if the warts do not go away after 4 weeks of treatment.
D.Immune-mediated therapies:
1.Both imiquimod and interferon initiate a local immune response at the site of the wart that ultimately may clear the lesions.
2.Imiquimod and topical interferon may be self-administered; injectable interferon is given in the office:
a.There are two formulas of imiquimod: Aldara (5% imiquimod) and Zyclara (3.75% imiquimod) are for treatment of external genital warts. Manufacturers recommend against vaginal administration. The choice between the two formulations should be made based on patient preference, cost, and convenience. The patient applies imiquimod cream directly to the clean dry warty tissue at bedtime. The cream is applied by rubbing into the wart, left on for 6 to 10 hours, then washed with mild soap. A mild, local inflammatory reaction (erythema, induration, ulceration/erosion, itching, burning, vesicles) should occur, which is a sign the drug is working: