Human Papillomavirus (HPV) Infection

Essentials

• Human papillomavirus (HPV) infection is very common. At least three out of four persons become infected during their lifetime. The infection is most common around the age of 20 to 25 years.
• HPV infection, in itself, is not a disease, but rather a risk factor.
• HPV infection resolves spontaneously in the majority of cases.
• Cervical cancer does not develop without a prior HPV infection. Cancer develops through premalignant stages.
• The stronger premalignant changes caused by HPV should be treated, mild changes may be followed up (tendency to spontaneous cure).
• Visible condylomata should be treated if they do not disappear spontaneously.
• HPV vaccine very efficiently prevents HPV infections HPV Vaccines Against Human Papillomavirus.
• Development of cancer can be prevented by finding and treating premalignant lesions through organized cervical cancer screening Pap (Cervical) Smear and Endometrial Biopsy.

Transmission and manifestation

• HPV is transmitted mainly in sexual contact
• There are almost 200 different strains of human papillomavirus (HPV).
• Time of transmission is impossible to determine (about 1 to 8 months, may be latent for years).
• The infection is most common at the age of about 20-25 years, but occurs even in 65-year-olds.
  • In Finland, 3% of 65-year-olds and about 8% of women screened between 30 and 65 years of age are HPV positive. Find out about local numbers.
• The average duration of an HPV infection in women of 13-23 years is 8 months. Up to 90% of infections heal within 2-3 years. Of changes detected in cytologic study and suggestive of HPV (ASC-US and LSIL), 85-91%, on average, heal without treatment within follow-up of 36-54 months.
• A prolonged HPV infection increases the risk of developing premalignant lesions and cancer.
• The infection usually presents as cellular changes invisible to the naked eye. These may be detected in women by Pap smear or by high-risk hrHPV test Pap (Cervical) Smear and Endometrial Biopsy. Much more rarely the infection may present with classical cauliflower-like warts, condylomata acuminata. In most cases the infection comes and resolves completely unnoticed.
• HPV infection is even more common in conditions involving immunosuppression (HIV, medication)

Symptoms

• The HPV-infection is almost always completely symptomless.
• The condylomata are often detected accidentally.
• Intense pruritus and ulcerations may rarely occur in the regions of vulva, anus and prepuce. These are usually caused by secondary infections.
• Urethral warts may cause burning on urination and haematuria.
• Some of the symptoms may be caused by other concurrent infections (Candida, herpes, Chlamydia).

Diagnosis

• HPV-infection in women is usually detected by hrHPV test or Pap smear Pap (Cervical) Smear and Endometrial Biopsy. A patient with repeated mild cellular change (ASC-US 2 or 3 times in 12 to 24 months) or a more substantial change (LSIL, ASC-H, HSIL or AGC) should be referred to colposcopy in order to detect potential premalignant lesion.
• Classical exophytic warts are usually readily diagnosed by the naked eye (pictures 1 2 3). It is advisable to examine also the anus (pictures 4 5; proctoscopy) and distal urethra (e.g. with a small nose speculum).
• Acetic acid application (3-5%) makes flat lesions visible as pale plaques (acetowhitening) in both sexes, but the finding is unspecific and difficult to interpret without a colposcope. Histological confirmation is needed for the diagnosis. The latter is not recommended as a clinical routine except in some situations because the majority of healthy adults bear the virus without having a disease.
• HPV DNA test can be used in cervical cancer mass screening and for follow-up after treatment of dysplasia and for triage of an ASC-US finding Human Papillomavirus Testing Versus Conventional Cytology for Cytological Cervical Lesions in women over 30 years of age.
• Biopsy is recommended (should be primarily taken in association with colposcopy)
  • when the patient has repeated mildly abnormal or worse findings on Pap smear (ASC-US or worse)
  • from naevus like lesions, especially if pigmented
  • from treatment-resistant warts
  • in patients with chronic symptoms (intensive itching, ulcerations).

Differential diagnosis

• Acetowhitening reactions may be seen in cases of unspecific infectious lesions and scar formation.
• Female external genitalia often show normal filamentous structures that are not associated with an HPV infection but are sometimes falsely interpreted as condylomata.
• About 30-40% of young men have papulae around the glans; these are not associated with HPV (picture6).
• Candida (itching, fissures), herpes (tender ulceration)
• Several skin diseases (e.g., lichen sclerosus et atrophicus, lichen planus, psoriasis, allergic eczema); see Benign Gynaecological Lesions and Tumours.

Management of condylomata

• Remember other sexually transmitted diseases!

Treatment of other HPV infections in the uterine cervix, vagina and vulva

• Treatment is determined by the colposcopy and histological findings.
• According to the Finnish guidelines, HPV changes (histological LSIL/CIN 1 and milder changes) are not treated because their spontaneous cure is highly probable.
• Premalignant lesions (histological HSIL/CIN 2/CIN 3) in the external os of the uterus are treated according to their extent and severity by removing them on colposcopy either with an electric loop or with laser (conization) on an outpatient basis. Scalpel conization should not be used.
  • In young (below 31 years) women, a histologic HSIL that after confirmation matches an earlier CIN 2 change and covers at maximum the area of 2/4 may be left untreated. These patients should be monitored closely at 6-month intervals for no longer than 2 years. In this patient group, CIN 2 changes have a 60% probability for regression.
• Vaginal lesions can be treated with laser (CO₂) in association with colposcopy.
• The premalignant HPV-lesions in the vulva or in the perineal or anal regions may also be treated with CO₂-laser using a colposcope.
• In some cases, lesions of the vagina and vulva can also be treated with imiquimod cream.

Treatment results

• Recurrence is detected in 3-8% of patients after the treatment of a premalignant lesion (CIN 2-3).
• The treatment does not affect fertility of a woman, but it may increase the probability of preterm delivery.
• Smoking significantly increases the risk of recurrence of a premalignant lesion.
• Recurrence is common after all treatments of condylomata.
• Screening and treatment of symptomless men does not affect the healing of mucosal lesions in their female partners.
• There are controversial results concerning the effect of condom use on the transmission of HPV or on the healing process.

Prevention

Screening to prevent cervical cancer

• The development of malignant cervical lesions can be effectively prevented by screening and treatment of the slowly progressing cellular abnormalities Population Screening for Cancer.
• More than 80% of cervical cancers and related deaths can be prevented by organized regular population screening based on Pap smears provided at intervals of 5 years.
• In Finland, cervical cancer screening programme targets women of 30-65 years at 5-year intervals. The screening programme is based on a decree. Ever growing number of municipalities have extend the screening to women of 25 years.
• The effectiveness of population-based screening is influenced by
  • good coverage of screening
  • good uptake of screening
  • good quality of diagnostics and clinical work.
• Organized screening is most effective in women aged 35 years or more.
• Also other than organized forms of screening (spontaneous or opportunistic screening) have a preventive effect on cancer but their cost-effectiveness is not as good as that of a screening programme.
• HPV testing instead of Pap smear testing brings in organized screening even better results than traditional screening based on Pap smears.
• Further investigations and the treatment of detected premalignant lesions form an essential part of screening.
• Approximately 99% of cervical cancers can be prevented by treatment of premalignant lesions.