A recent study by Mbulawa et al (2022) show that HPV-35 is the third most dominant type among South African women with cervical intraepithelial lesion (CIN)-2, the second most dominant type among women with CIN-3 (22.2%) and the fourth most dominant type among women with CCa.² 

What is concerning is that it is unclear if current vaccines offer protection against HPV-35. Fitzpatrick et al caution that more studies are needed to ascertain coverage by available HPV vaccines.^2,3  

Mortality rate twice as high in African countries 

In the United States, 40% and in the United Kingdom, 42% of women diagnosed with CCa die from the disease, while in Africa the death rate is almost twice as high (78%).³ 

Apart from being the leading cause of mortality among South African women, CCa is the second most frequent cancer among women of reproductive age (15- and 44-years), after breast cancer.³ 

Young women at higher risk of CCa 

Studies report that 80%-90% of women will have HPV at some point in their life, of which 3%–4% will develop CCa. Young women are particularly at high risk of CCa because they tend to be more sexually active and have higher numbers of sexual partners compared to older women. Early exposure to sexual intercourse and multiple sex partners are both known risk factors for HPV.⁴ 

Other factors for increasing young women’s susceptibility to cervical dysplasia include smoking, oral contraceptive use, and vulnerability of the adolescent cervix to sexually transmitted infections.⁴ 

There also seems to be a lack of awareness about CCa among young women and the need for regular screening. Young women also seem to have negative or inaccurate beliefs or attitudes about Pap testing.⁴  

A study conducted among female university students found that 42.9% of the participants had heard of CCa, but only 9.8% had ever had a Pap smear. Furthermore, only around 20% of South African women over 30 has ever been screened.⁴ 

Early screening can save millions of women  

Early screening of CCa is an important preventative strategy. The World Health Organization’s (WHO) global strategy for CCa elimination calls for 70% of women globally to be screened regularly for cervical disease with a high-performance test, and for 90% of those needing it to receive appropriate treatment.^2,5  

Alongside vaccination of girls against HPV, implementing this global strategy could prevent more than 62 million deaths from CCa in the next 100 years, according to the WHO.⁵ 

Recommended screening approaches 

The WHO recommends two approaches to screening and treatment:⁵  

1. The screen-and-treat approach  
2. The screen, triage and treat approach. 

In a screen-and-treat approach, treatment is provided based on a positive primary screening test alone, without triage (eg no second screening test and no histopathological diagnosis).⁵  

When the patient is eligible for ablative treatment, this should ideally be done immediately, at the same visit as the screening test (the single-visit approach). At some facilities, this is not feasible and a second visit is needed (the multiple-visit approach).⁵  

Women who are not eligible for ablation can have excisional treatment on the same day if the clinic has the capacity for large-loop excision of the transformation zone (LLETZ). If LLETZ is not available on-site, women need to be referred for the excisional treatment or for further evaluation.⁵  

In a screen, triage and treat approach, the triage test is done if the primary screening test is positive, and the decision to treat is made when both the primary test and the triage test are positive.⁵   

A positive triage test can lead to colposcopy with biopsy and histopathological examination for diagnosis to determine the appropriate treatment. The implementation of colposcopy and biopsy can be challenging, however, so this guideline also considers triage strategies that are not dependent on the availability of colposcopy.⁵  

When the primary screening test is positive, and the triage test is negative, women need appropriate follow-up evaluation at a specified date according to the recommendations.⁵ 

Screening recommendations for the general population of women 

The WHO recommends:⁵  

• Regular screening from the age of 30.  
• Women (50-59-years) who have never been screened, should be prioritised.⁵  
• After the age of 50, screening can be stopped after two consecutive negative screening results. 
• HPV DNA detection, rather than visual inspection with acetic acid (VIA) or cytology should be used as the primary screening test either with triage or without triage and treatment approaches among both the general population and women living with HIV. The estimated sensitivity of HPV DNA testing is higher than that of conventional Pap smear (68.1% vs 40.2%).⁶ 
• Women who are HIV- should be screen every five to ten years when using HPV DNA detection as the primary screening test. 
• Where HPV DNA testing is not yet operational, regular screening interval of every three years when using VIA or cytology as the primary screening test, is recommended for all women. 
• Women who have screened positive on an HPV DNA primary screening test and then negative on a triage test should be retested with HPV DNA testing at 24 months and, if negative, move to the recommended regular screening interval. 
• Women who have screened positive on a cytology primary screening test and then have normal results on colposcopy should be retested with HPV DNA testing at 12 months and, if negative, move to the recommended regular screening interval. 

The South African CCa guideline recommends both cervical  cytology  and  HPV  testing. Screening  practitioners  or  facilities   should   choose   the   most   appropriate   test   for   their   setting.⁷ 

Appropriate triage or secondary tests for  South  Africa  include  cytology,  HPV  test,  immuno-cytochemistry, or VIA. Triage is usually performed with a different test to the initial screening test and treatment facilities should choose the most appropriate for  their  setting. Repeat  cytology  is  appropriate  triage  after  medium risk cytology.⁷ 

How can screening be improved? 

Lott et al analysed three types of interventions commonly used in Africa to encourage women to go for regular CCa screening:⁸ 

1. Health education interventions  

They found that overall, educational interventions were not very effective with the exception of programmes that included peer health educators or community health educators. In order to be successful, educational interventions have to be intensive, culturally-appropriate, based on health behaviour models, and multi-dimensional so that they help women to overcome environmental constraints. One way to overcome environmental constraints for example is to find ways to meaningfully engage with male partners and relatives to increase cervical screening in women. For example, a study found that father-in-laws and husbands, play an important role in decision-making related to Pap smear uptake in South Africa.  

2. Economic incentivisation interventions  

Economic incentivisation interventions were moderately effective, increasing uptake but still achieving less than 20% coverage. With only two studies incentivising screening, there is also a paucity of evidence for this intervention type. Removing costs and increasing women’s perceived benefits of screening does lead to increased uptake of screening, but the low post-intervention coverage indicates that further action is needed to reach desirable coverage. This approach may be combined with other types of interventions in the future, like those that consider environmental constraints and act on instrumental attitude simultaneously. 

3. Innovative service delivery interventions 

Innovative service delivery interventions worked by changing the location of screening services, or by combining screening services with other health services such as voluntary male circumcision and HPV vaccination. Innovative service delivery approaches should focus on the availability, accessibility, and appropriateness of screening services for women, acting on the integrated behavioural model construct of environmental constraints. 

Conclusion 

With a comprehensive approach to prevent, screen, and treat, CCa can be eliminated as a public health problem within a generation, states the WHO. A comprehensive approach should include early diagnosis and effective management.⁹  

Effective management includes primary (HPV vaccination) and secondary prevention approaches (screening for, and treating precancerous lesions), which will prevent most CCa cases.⁹ 

REFERENCES 

1. Hopkins KL, Jaffer M, Hlongwane KE, et al. Assessing national cervical cancer screening guidelines: Results from an HIV testing clinic also screening for cervical cancer and HPV in Soweto, South Africa. PLOS ONE, 2021. 
2. Mbulawa ZZA, Phohlo K, Garcia-Jardon M, et al. High human papillomavirus (HPV)-35 prevalence among South African women with cervical intraepithelial neoplasia warrants attention. PLOS ONE, 2022. 
3. Fitzpatrick MB, Hahn Z, Mandishora RSD, et al. Whole-Genome Analysis of Cervical Human Papillomavirus Type 35 from rural Zimbabwean Women. Nature Scientific Reports, 2020. 
4. Akokuwebe ME, Idemudia ES, Lekulo AM and Motlogeloa OW. Determinants and levels of cervical Cancer screening uptake among women of reproductive age in South Africa: evidence from South Africa Demographic and health survey data, 2016. BMC Public Health, 2021. 
5. World Health Organization. WHO guideline for screening and treatment of cervical pre-cancer lesions for cervical cancer prevention, second edition. Geneva: World Health Organization; 2021. Licence: CC BY-NC-SA 3.0 IGO. 
6. Kulasingam SL, Hughes JP, Kiviat NB, et al. Evaluation of Human Papillomavirus Testing in Primary Screening for Cervical AbnormalitiesComparison of Sensitivity, Specificity, and Frequency of Referral. JAMA, 2002. 
7. Botha MH ad Dreyer G on behalf of the SA HPV Advisory Board. Guidelines for cervical cancer screening in South Africa. Southern African Journal of Gynaecological Oncology, 2017. 
8. Lott BE, Trejo MJ, Baum C, McClelland DJ. Interventions to increase uptake of cervical screening in sub-Saharan Africa: a scoping review using the integrated behavioral model. BMC Public Health, 2020. 
9. World Health Organization. Cervical Cancer. https://www.who.int/health-topics/cervical-cancer#tab=tab_1