HPV infection: vaccination and prevention of cervical cancer

What is HPV and how is it linked to cervical cancer?

Human papillomavirus (HPV) is the most common sexually transmitted infection: more than 80% of sexually active people are infected with at least one type of HPV during their lifetime. More than 200 types of HPV are known, of which around 40 affect the anogenital area. The high-risk oncogenic types — above all HPV-16 and HPV-18 — are responsible for 70% of cases of cervical cancer, and for a substantial share of cancers of the vulva, vagina, anal canal, penis and oropharynx. According to WHO data, cervical cancer is the fourth most common cancer among women worldwide: more than 604 000 new cases and 342 000 deaths are recorded each year. In Ukraine around 5 000 new cases of cervical cancer are found each year, and mortality reaches 2 000 women a year. Most HPV infections are transient — the immune system clears the virus within 1–2 years. Persistent infection with high-risk types, however, can cause progressive dysplasia of the cervical epithelium (CIN I → CIN II → CIN III), which without treatment transforms into invasive cancer over 10–20 years. Risk factors for persistence are immunosuppression, smoking, co-infection with other STIs, long-term use of oral contraceptives and a large number of sexual partners.

Types of HPV and the clinical features of infection

The clinical features of HPV infection depend on the type of virus, the site involved and the state of the patient's immune system:

• Low-risk HPV (types 6, 11): cause anogenital warts (condylomata acuminata) — benign growths on the skin and mucous membranes of the external genitals, perineum and perianal area. Warts appear as soft papillomatous growths on a stalk or a broad base; they may be single or multiple and may merge into masses resembling a cauliflower. The incubation period is 3 weeks to 8 months. In children, HPV-6 and HPV-11 can cause recurrent respiratory papillomatosis of the larynx — a rare but serious disease.
• High-risk HPV (types 16, 18, 31, 33, 45, 52, 58): persistent infection with these types is a necessary condition for cervical cancer to develop. Cervical intraepithelial neoplasia (CIN) is usually symptomless and is found only on screening. HPV-16 is associated mainly with squamous cell carcinoma, HPV-18 with adenocarcinoma of the cervix. Besides cervical cancer, high-risk types are responsible for 90% of anal cancers, 70% of oropharyngeal cancers, 40% of cancers of the vulva and vagina and 50% of penile cancers.
• Subclinical HPV infection: most HPV infections are symptomless — the virus is detected only by molecular methods. Subclinical cervical lesions are seen at colposcopy after applying acetic acid, as acetowhite areas. Latent infection can reactivate with immunosuppression, in pregnancy or with age. It is precisely this symptomless course that makes regular screening critical for the early detection of pre-cancerous change.
• Particular clinical forms: HPV-associated oropharyngeal cancer (mainly HPV-16) is a rapidly growing problem, particularly among men: in some developed countries its incidence has overtaken cervical cancer. It presents with a sore throat, difficulty swallowing and enlarged neck lymph nodes. Bowenoid papulosis — multiple pigmented papules on the external genitals associated with HPV-16 — has malignant potential. Buschke–Löwenstein giant condyloma is a rare destructive form resembling verrucous carcinoma.

Screening and diagnosis of HPV-associated pre-cancerous conditions

Effective cervical cancer screening is the key element of secondary prevention, allowing pre-cancerous change to be found at a stage when treatment is minimally invasive and highly effective. The HPV test (molecular screening) detects DNA or mRNA of high-risk HPV types in samples from the cervical canal. WHO recommends the HPV test as the priority screening method at intervals of 5–10 years for women from the age of 30. Its sensitivity for detecting CIN II+ is 95–100%, considerably higher than cytological screening. A negative HPV test has a high negative predictive value — the risk of developing CIN III over the next 5 years is less than 1%. The Pap test (cytological screening) is microscopic examination of cells from the surface of the cervix and the cervical canal. Results are classified by the Bethesda system: NILM (normal), ASC-US, LSIL, HSIL, AGC, AIS. It is recommended every 3 years for women aged 21–29. Sensitivity for CIN II+ is 50–70% on a single test, but serial screening substantially increases cumulative effectiveness. Co-testing (HPV test plus Pap test) has the highest sensitivity for detecting pre-cancerous conditions. It is recommended for women aged 30–65 at 5-year intervals. Colposcopy with biopsy is the diagnostic procedure used to establish the nature and degree of dysplastic change after a positive screen. Targeted biopsy with histology is the gold standard for confirming CIN. Genotyping for HPV-16/18 after a positive HPV test allows risk to be stratified and further follow-up to be planned.

HPV vaccination: types of vaccine and effectiveness

Preventive vaccination against HPV is the most effective method of primary prevention of cervical cancer and other HPV-associated diseases. The bivalent vaccine (Cervarix) targets HPV-16 and HPV-18 and provides cross-protection against types 31, 33 and 45. Its effectiveness in preventing CIN II+ is 93–100% in those not previously infected. Long-term immunogenicity is proven — antibodies persist for at least 12 years after vaccination. The quadrivalent vaccine (Gardasil) protects against HPV-6, 11, 16 and 18. Besides preventing cervical cancer, it is effective against 90% of genital warts (types 6 and 11). The nonavalent vaccine (Gardasil 9) offers the broadest protection: HPV-6, 11, 16, 18, 31, 33, 45, 52 and 58. It can potentially prevent 90% of cervical cancers (compared with 70% for the bivalent vaccine). WHO recommends it as the priority vaccine. The vaccination schedule: for those aged 9–14, 2 doses 6–12 months apart; for those aged 15 and over, 3 doses (at 0, 1–2 and 6 months). In 2022 WHO approved a single-dose schedule on the basis of new data showing that one dose is sufficiently effective, which simplifies the implementation of vaccination programmes. The optimal age for vaccination is 9–14, before sexual activity begins, when effectiveness is greatest. Vaccination is also recommended for boys — to prevent HPV-associated cancers and genital warts, and to build herd immunity.

Comprehensive prevention of cervical cancer

The WHO strategy for eliminating cervical cancer as a public health problem sets three key targets to be reached by 2030: 90% of girls fully vaccinated by the age of 15, 70% of women screened with a high-performance test by 35 and again by 45, and 90% of women with identified pre-cancerous conditions or cancer receiving appropriate treatment. Primary prevention — HPV vaccination remains the most effective tool. Australia, the first country in the world to introduce a national HPV vaccination programme in 2007, shows impressive results: the incidence of cervical cancer has fallen by 50% in vaccinated cohorts, and genital warts have practically disappeared among young people. Secondary prevention — regular screening with an HPV test or a Pap test according to the age-based recommendations. Women aged 21–29: a Pap test every 3 years. Women aged 30–65: an HPV test every 5 years, or co-testing every 5 years, or a Pap test every 3 years. After 65, screening may be stopped provided previous screening was adequate and there is no history of CIN II+. Tertiary prevention — timely treatment of pre-cancerous conditions (CIN II/III) using excisional methods: loop electrosurgical excision (LEEP/LLETZ) and cervical conisation. Cryotherapy is an alternative where resources are limited. Additional measures — stopping smoking, barrier contraception, limiting the number of sexual partners and supporting the immune system — reduce the risk of HPV persisting and of dysplasia progressing.

When to see a gynaecologist

See a gynaecologist about routine HPV vaccination — the optimal age for vaccinating girls and boys is 9–14, but vaccination is effective up to the age of 26 (and, on a doctor's advice, up to 45). Even if you have already had sexual contact, the vaccine protects against the HPV types you are not yet infected with. See a doctor immediately if you develop unusual vaginal discharge, bleeding after intercourse, bleeding between periods or lower abdominal pain — these symptoms may indicate pre-cancerous change or early cervical cancer. Do not put off a visit if wart-like growths have appeared on the external genitals — genital warts need treatment and monitoring, even if they cause no discomfort. Have regular cervical cancer screening according to the age-based recommendations — an HPV test or a Pap test detects pre-cancerous change at an early stage, when treatment is minimally invasive and highly effective. Women with a positive HPV test need further assessment (colposcopy) even without symptoms — persistent infection with high-risk types requires ongoing follow-up. Remember: cervical cancer is a disease that can be prevented through vaccination and regular screening. Ukraine is gradually introducing an HPV vaccination programme — ask your doctor about the availability of the vaccine.