HPV infection is also associated with a number of other diseases, including cutaneous and anogenital warts and cancer (anus, vulva, vagina, and penis) as well as head and neck (oral cavity, oropharyngeal, and larynx) cancer.^4,5 

Preventing cervical cancer 

Primary and secondary prevention measures include vaccinations against HPV, and screening.¹  

Primary prevention 

Current vaccines cover HPV types that are related to about 90% of all CCa. The three types of approved HPV vaccines, including bivalent, tetravalent, and 9-valent vaccines, are effective in reducing HPV infection and HPV-related disease incidence.^1,4 

Secondary prevention 

The Pap smear is probably the best known screening method and the decline in CCa incidence globally, has been largely attributed to this test, developed in the 1920s. One of the main disadvantages of a Pap smear is that it has a high false-positive rate.^1,6  

Other disadvantages of a Pap smear is it invasiveness, that it does not test for all of the different strains of HPV that can cause CCa, and that it does not test for HPV on its own.⁶   

An alternative to the Pap smear is liquid-based cytology (LBC). Advantages of LBC is that it is less invasive, has greater sensitivity regarding the detection of pre-cancerous lesions, resulting in a reduced incidence of CCa. It can also be used for further examinations.¹  

Cytology testing is the mainstay of CCa screening in South Africa. The national screening policy allows for three cytological test in a woman’s life-time and each screening occurs every 10 years between the ages of 30 to 65 year.³   

A number of countries have implemented a HPV-testing with cytology triage strategy. With HPV-based screening, tests can detect the presence of HPV DNA or RNA in a sample of cervical cells, with a positive result indicating an HPV infection. ²  

HPV-testing is significantly more sensitive than cytology to predict CCa and its precursors. The sensitivity of the test is >90% due because of the ability of polymerase chain reaction to detect HPV DNA even when present in extremely small quantities.³  

Why are women unwilling to go for screening? 

Despite advances in the prevention, screening, and detection of CCa, women are still hesitant to undergo screening. To try to answer this conundrum, Nothacker et al conducted a systematic review to identify women’s concerns - specifically about HPV-based screening.² 

The team found that some women:² 

• Underestimate their risk of being infected with HPV and therefore see no reason to be screened.  

• Fear that being tested might lead to stigmatisation such as mistrust and infidelity. 

• Who understand the purpose of screening, describe feeling anxious and distressed about the results of a test with some indicating that they did not know what a positive test result means.

Patient education essential 

According to Nothacker et al, patient education is crucial to improve the uptake of CCa screening among women. Educational programmes should focus on the following:² 

What is the prevalence of HPV?  

In their lifetime, sexually active women and men will be infected at least once. The global prevalence of HPV infection in women ranges from 3.5%-45%. In men, the global prevalence rate of HPV infection is 2%-44%.⁴  

HPV lives in the skin and the cells lining the inside of our bodies and infection is quite common. HPV can be dormant for a period (a couple of years but can stretch to decades), without causing any harm, but it can become active later, which is when it would be picked up in cervical screening.⁷ 

As mentioned above, there are more than 100 different HPV strains. Strains are categorised as low risk, which mostly cause no disease. However, a few low-risk HPV types can cause warts on or around the genitals, anus, mouth, or throat.⁷ 

High-risk HPVs can cause several types of cancer. There are about 14 high-risk HPV types including HPV 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66, and 68. Two of these, HPV16 and HPV18, are responsible for most HPV-related cancers.⁷ 

Adolescent girls and women under 25 are at highest risk. In South Africa, the prevalence of HPV prevalence (low and high-risk) ranges from 44% to 85% among adolescents and young women (15- to 25-years).^4,8  

What causes HPV infection and how is it transmitted? 

Transmission of HPV can occur through direct or indirect skin, or sexual contact. The latter is the main cause of infection.⁵ 

Co-infection with Chlamydia trachomatis and herpes simplex virus type-2, immunosuppression, and certain dietary deficiencies are other probable cofactors. Genetic and immunological host factors and viral factors other than type, such as variants of type, viral load, and viral integration, are likely to be important but have not been clearly identified.⁵ 

Vertical transmission occurs when a parent conveys an infection to an unborn offspring, including a special form of vertical transmission - perinatal infection.⁹ 

What are the risk factors for an HPV infection?  

While it is true that women who have never been sexually active rarely develop CCa, any woman who has had at least one sexual partner is potentially at risk for HPV infection and CCa and therefore should be screened regularly.² 

Risk factors include:^5,10 

• Multiple sexual partners at any time or is the partner of someone who has had multiple sexual partners 
• Sexual activity at an early age 
• A history of other sexually STIs, genital warts, abnormal Pap smears, or cervical or penile cancer in an individual or sexual partner 
• Tobacco smoking  
• High parity 
• Long-term hormonal contraceptive use 
• Co-infection with HIV. 

It should be noted that condom use may not adequately protect individuals from exposure to HPV since HPV can be transmitted by contact with an infected person.¹⁰ 

What does a positive Pap test result mean? 

More than 95% of women who develop CCa test positive for HPV. A Pap smear shows whether cervical cells are normal or abnormal. A normal Pap smear result indicates that no abnormal cervical cells were found.^11,12   

A abnormal or positive Pap smear result just means that the patient has an infection, it does not mean that she has CCa, but it does warrant further testing. Follow-up tests and procedures after an abnormal/positive result include:¹² 

1. Colposcopy 

The main aim of a colposcopy is to identify precancerous and cancerous lesions so that they may be treated early. 

1. Cervical biopsy 

Biopsy samples are checked by a pathologist for cervical intraepithelial neoplasia (CIN). CIN refers to abnormal cervical cells that were found on the surface of the cervix after a biopsy.¹²  

CIN is graded on a scale of 1 to 3, based on how abnormal the cells look under a microscope and how much of the cervical tissue is affected. Low-grade intraepithelial lesion changes seen on a Pap test are generally CIN1. High-grade intraepithelial lesion changes seen on a Pap test can be CIN2, CIN2/3, or CIN3. CIN1 changes are mild, or low grade. They usually go away on their own and do not require treatment.¹² 

CIN2 changes are moderate and are typically treated by removing the abnormal cells. However, CIN2 can sometimes go away on its own. CIN2 must be treated if it progresses to CIN3 or does not go away in one to two years.¹² 

CIN 3 changes are severely abnormal. Although CIN3 is not cancer, it may become cancer and spread to nearby normal tissue if not treated. Doctors do not yet have a way to tell which cases of CIN3 will become cancer and which will not. CIN3 should be treated right away unless the patient is pregnant.¹²  

What are the benefits and drawbacks of cytology vs HPV-testing?  

HPV-testing is done during a pelvic examination, using a small brush to collect a sample from the cervix, or on a vaginal sample self-taken by a woman, which offers an opportunity to improve screening coverage.¹³ 

The sample is sent to a laboratory for genotyping. An HPV-test only detects evidence of an infection with a high-risk strain of HPV. Virtually all CCa are caused by high-risk HPV strains.^13,14 

Randomised trials show that HPV testing detects more cervical precancers and prevents more CCa than cytology-based screening does. By increasing the detection of high grade CIN (2 or higher) at an earlier stage, HPV testing can prevent more cases of CCa and therefore, screening intervals can be extended.^13,14 

The benefits and drawbacks of Pap smears and LBC were alluded to above. A drawback of HPV testing, however, is that most HPV infections are transient, and therefore HPV-based screening has lower specificity and may increase colposcopy referrals compared with cytology-based screening.¹³  

Unnecessary colposcopies should be avoided because they can be associated with psychosocial and physical discomfort and may ultimately lead to overtreatment of regressive cervical intraepithelial neoplasia.¹³ 

According to Dreyer et al HPV screening strategies can positively impact the burden and epidemiology of CCa and maternal health within South Africa.³ 

REFERENCES  

1. Wang W, Arca E, Sinha A, et al. Cervical cancer screening guidelines and screening practices in 11 countries: A systematic literature review. Preventative Medicines Report, 2022. 
2. Nothacker J, Nury E, Mathieu MR, et al. Women’s attitudes towards a human papillomavirus-based cervical cancer screening strategy: a systematic review. BMJ Sexual and Reproductive Health, 2022. 
3. Dreyer G, Maske C, Stander M. Clinical evaluation, and budget impact analysis of cervical cancer screening using cobas 4800 HPV screening technology in the public sector of South Africa. PLoS One, 2019. 
4. Kombe KAJ, Li B, Zahid A, et al. Epidemiology and Burden of Human Papillomavirus and Related Diseases, Molecular Pathogenesis, and Vaccine Evaluation. Frontiers Public Health, 2021. 
5. Bruni L, Albero G, Serrano B, et al. ICO/IARC Information Centre on HPV and Cancer (HPV Information Centre). Human Papillomavirus and Related Diseases in South Africa. Summary Report 22 October 2021.  
6. Phadke A. Cervical Cancer Screening: An analysis Liquid-based cytology (LBC) + HPV test v/s Conventional Pap smear test. https://phadkelabs.com/blog/cervical-cancer-screening-an-analysis-liquid-based-cytology-lbc-hpv-test-v-s-conventional-pap-smear-test/ 
7. Cancer Research UK. Let’s talk about HPV: 6 common questions answered. https://news.cancerresearchuk.org/2021/06/16/lets-talk-about-hpv-6-common-questions-answered/#:~:text=HPV%20has%20a%20'dormancy'%20period,picked%20up%20in%20cervical%20screening. 
8. Mbulawa ZZA, Somdyala NI, Mabunda S, Williamson A-L. High human papillomavirus prevalence among females attending high school in the Eastern Cape Province of South Africa. PLoS One, 2021. 
9. IARC Working Group on the Evaluation of Carcinogenic Risks to Humans. Human Papillomaviruses. Lyon (FR): International Agency for Research on Cancer; 2007. (IARC Monographs on the Evaluation of Carcinogenic Risks to Humans, No. 90.) 3, Studies of Animal Papillomaviruses. 
10. Burd EM. Human papillomavirus and cervical cancer. Clin Microbiol Rev. 2003. 
11. Legood, R, Gray, A, Wolstenholme, J, and Moss, S. Lifetime effects, costs, and cost-effectiveness of testing for human papillomavirus to manage low grade cytological abnormalities: results of the NHS pilot studies. BMJ, 2006. 
12. National Cancer Institute. HPV and Pap Test Results: Next Steps after an Abnormal Cervical Cancer Screening Test. https://www.cancer.gov/types/cervical/screening/abnormal-hpv-pap-test-results 
13. Feldman S, Goodman A, Peipert JF, et al. Patient education: Cervical cancer screening (Beyond the Basics). UpToDate, 2022. https://www.uptodate.com/contents/cervical-cancer-screening-beyond-the-basics 
14. Thomsen LT, Kjær SK, Munk C, et al. Benefits and potential harms of human papillomavirus (HPV)-based cervical cancer screening: A real-world comparison of HPV testing versus cytology. AOGS, 2021.