Cervical cancer in Zimbabwe: a situation analysis

Introduction Despite the wide-spread availability of cervical cancer prevention and screening programs in developed countries, the morbidity and mortality rates of cervical cancer in Zimbabwe are still very high. Limited resources as well as the high HIV prevalence are contributors to the high burden of cervical cancer. This paper aims to analyse the policies, frameworks and current practices in the management of cervical cancer in Zimbabwe. Methods A review of national documents and published literature on cervical cancer prevention, screening, treatment and knowledge in Zimbabwe was done. Informal interviews were conducted to assess the practices of cervical cancer management. Results Through strategic collaboration, a pilot for the HPV vaccination program is underway. The VIAC national cervical cancer screening program is being adopted into the current healthcare system. With regards to the treatment of precancerous lesions we found that the "see and treat" program has been implemented in colposcopy clinics. In addition, there are two multidisciplinary cancer treatment clinics installed in two central public hospitals. The general knowledge and understanding of cervical cancer is poor in Zimbabwe. Conclusion Limitations in resources, infrastructure, manpower, delays in treatment and patient knowledge play a role in the high morbidity and mortality of cervical cancer in Zimbabwe. The Ministry of Health needs to increase funding to expedite the availability of HPV vaccine and screening programs. Community engagement initiatives to raise awareness on cervical cancer should be established to provide education on how to prevent the development of cervical cancer, as well as promote screening for early detection.


Introduction
Cervical cancer is the fourth most commonly diagnosed cancer among females worldwide [1]. In 2012, the International Agency for Research on Cancer (IARC) recorded 527,624 new cervical cancer cases and 265,672 related deaths [2]. An estimated 90% of the globally recorded cervical cancer-related deaths are in low-and middle-income countries (LMICs), for which 8 in 10 are recorded within the Sub-Saharan African region [3,4]. The morbidity and mortality of cervical cancer is much lower in developed countries due to availability of efficient and accessible screening programs as well as diagnostic and treatment facilities [5]. Meanwhile, in LMICs where the bulk of global cervical cancer cases are diagnosed (>85%) there is a poor survival rate attributable to late presentation at diagnosis and patients not receiving or completing their prescribed treatment regimens [6]. In LMICs there are challenges in affordability and availability of drugs, as well as access to treatment facilities [7][8]. The biggest risk factor of cervical cancer is human papillomavirus (HPV), commonly detected in cervical tumour specimens. The sexually transmitted infection, genital warts that are caused by high-risk HPV subtypes, have been shown to present with a 99% chance of progressing to cervical cancer [9]. Administering broad-spectrum HPV vaccines to adolescents in developed countries such as France, Iceland, Norway, Switzerland, UK and USA has decreased the prevalence of cervical cancer, thus proving successful as a preventive measure [10].
Global trends show that most cervical cancer high-risk countries are in Africa especially Malawi, Mozambique, Zambia and Zimbabwe [11]. Similar to worldwide statistics, cervical cancer is the most frequently occurring cancer in women of all races and ages in Zimbabwe, with a burden of 19% [12]. In black women cervical cancer contributes to 35.5% of all cancers while in non-black women it accounts for 2.8% [12]. It is estimated that 2270 women are diagnosed with cervical cancer in Zimbabwe annually and a mortality rate of 64% has been recorded [13]. The burden and mortality rate of cervical cancer is most likely to be higher than those recorded in the national cancer registry because some cases go unreported in areas that have poor access to health facilities such as rural areas [14]. The burden of cervical cancer is still very high in Zimbabwe mainly as a result of late presentation of disease, poor screening, diagnosis and treatment facilities which is compounded by the very high HIV incidence. In 2015, 1.4 million people were estimated to be living with HIV in Zimbabwe, and HIV augments the risk of malignancy by 10% [15,16]. There is a host of articles to address and report on prevention, screening and treatment in biomedical, behavioural and policy level findings of cervical cancer that have been published in different settings. The aim of this paper is to conduct a situation analysis on cervical cancer in Zimbabwe by reviewing the policy frameworks and practices in prevention, early detection and treatment of cervical cancer. This paper will highlight successes and challenges in the prevention and progressive management of cervical cancer in Zimbabwe. were about cervical cancer prevention, screening and treatment in Sub-Saharan Africa. Duplicates were eliminated. Emphasis was made on publications that were focussing on Zimbabwe (81 publications), for which 60 full articles were available for review.

Methods
The inclusion criteria for articles to be used for this study were the cervical cancer-related publications about Zimbabwe. Searches in the databases used key terms "Cervical cancer + Zimbabwe"; "Cervical Cancer + sub-Saharan Africa"; "Cervical cancer + Africa"; "HPV vaccine in Zimbabwe"; "VIAC + Zimbabwe"; "Screening +

Results
Findings of studies published about cervical cancer in Zimbabwe are summarised in Table 2

Discussion
Prevention: The most effective preventive strategies intercept the initial offset of cervical cancer by inhibiting the activity of the causative agent [17][18][19]. HPV has been implicated as the main aetiological factor in 99% of cervical cancer cases [20]. Seven HPV subtypes account for 87% of cervical cancer and HPV16/18 collectively contribute to 70% [21]. Seventy out of one hundred and ninety-six countries implemented HPV vaccinations as national programs [22]. Zimbabwe is one of the countries that are still in the pilot phase for a three-dose schedule for Cervarix (HPV16/18) and Ordasit (HPV6/11/16/18) HPV vaccine programme [23]. Over 35% of women contract HPV within two years of on-setting sexual activity so this pilot in Zimbabwe targets 10 year old girls or girls that have not lost their virginity [24][25][26][27]. The vaccine is safe to administer to immunocompromised individuals [28]. It is hoped that these vaccination programs will lead to a decrease in cervical cancer which can then incentivise the Ministry of Health to mobilise resources for national implementation. Since the national HPV vaccine programme in Australia, the incidence of genital warts has significantly decreased in women < 27years [29]. Correspondingly, cervical cancer has decreased in USA, UK, Switzerland and Austria since implementing the national vaccination programme [30][31][32][33].
South Africa and Botswana [34,35] [36,37]. While there is a possibility of cross-protection, it is not guaranteed to prevent pathogenesis of the HPV subtypes that are not targeted by these vaccines. Additionally, 17% of HPV-related cancers are caused by two or more HPV subtypes, thus cross-protection may unlikely be dependable [38].
The nanovalent vaccine to target HPV6, 11,16,18,31,33,45,52 and 58 was approved targeting five HPV types that are prevalent in Page number not for citation purposes 4 Zimbabwe, thus may be more beneficial compared to the available vaccines [39,40].
HPV vaccines are expensive and available in private healthcare in Zimbabwe ( Table 3). Majority of Zimbabweans are informally employed, of low socioeconomic status and rely heavily on the erratic public healthcare. Lacking national vaccination programmes in the public health sector socioeconomically discriminates against the public health sector clientele by limiting the knowledge of and accessibility to such services. Therefore, in order to make vaccines available to all women, regardless of socioeconomic status, the vaccination programs need to expand into the public sector, at a lower price through subsidiary funding from the government or donors. With provision of subsidiary funds and political motivation, an intensive vaccination campaign model can be adopted from neighbouring LMICs such as Botswana. The vaccination was carried out bi-annually, in country-wide clinics and schools on set dates (over a week period) in Botswana, ensuring a wide coverage in limited time [34].
Knowledge about cervical cancer is varied among Zimbabweans, with some women from rural areas describing cervical cancer as" a dirtiness of the womb caused by sperm" and some further alluding to the cause as; "vaginal preparations, multiple sexual partners, cold weather and witchcraft" ( Table 2) [41]. This poor understanding along with the misconceptions of what cancer and cervical cancer is, leads to poor health seeking behaviour. Therefore, it is important to conduct education and awareness campaigns to improve the knowledge, attitudes and perceptions of cervical cancer. This is supported by findings that after education on cervical cancer, Taiwanese women were interested in HPV vaccination programs, under the condition of personal discretion [42]. Similarly Nigerian women, after education on HPV reported they would recommend the vaccine to their female children [43]. It is very common in conservative cultures not to address issues that concern reproductive health. Furthermore, because the HPV vaccine targets minors, assent is required before vaccination therefore reproductive health education should be conducted at community and school levels for better sociocultural acceptance. Health issues among Zimbabweans traditionally are not seen as individual concerns, but as familial or community challenges. Thus acceptability at family and community level is a primer for success of any health initiatives.
Screening: Early detection can be achieved by conducting regular screening [44]. WHO proposes screening to identify asymptomatic precancerous lesions such as cervical intraepithelial neoplasia (CIN) between 30-49 years regardless of HPV vaccination status [45].
Several cervical cancer screening methods can be used, and can be classed into cytological tests-papanicolau smear test (Pap smear); liquid based cytology; visual inspection tests-acetic acid (VIAC) and Lugol's iodine (VILI); and HPV DNA testing [46]. Pap smear is one of the most reliable and effective screening methods. In developed countries, national pap smear screening programs have significantly decreased the burden of cervical cancer [47] while LMICs have been unsuccessful in implementing such programs [34,48]. In particular, administering pap smear as routine care has decreased the incidence of cervical cancer in UK, Switzerland, USA and Australia [31,49]. However, pap smears were not easily adopted into routine care in the public health sector in Zimbabwe due to limitations in resources and lack of skilled cytopathologists and cytotechnologists to conduct the smear analysis [50].
The use of contraceptives induces cervical inflammation resulting in CIN, a precursor to cervical cancer [51][52][53]. In Zimbabwe pap smears were routine care for women on the injection contraceptive Depo-Provera, from 1987 until late 1990s but was halted due to inadequate resources [54]. In addition other primary care facilities and district hospitals previously offered pap smears to women six weeks post-delivery, which was terminated due to lack of relevant infrastructure and resources [55]. These challenges resonate with challenges in other LMICs like Nigeria, India and Ghana causing non-screening using pap smears [56]. In 2017, pap smears are still offered in Zimbabwe at family planning clinics subject to availability of consumables or through specialists and gynaecologists at costs indicated in Table 3. Additionally, medical aid societies subsidise the cost of pap smears however, this has low impact on prevention because the number of individuals subscribed to medical aid is very low due to financial constraints. It is recommended that between 21-65 years, women undergo cytological testing every three years and HPV co-testing every five years after 30 years [57]. HPV cotesting increases the chance for HPV detection and CIN diagnosis by 30% [14].
This could be done in Zimbabwe with the regular service provided by one private laboratory, Lancet, however these tests are expensive and beyond reach for the majority who need them. In light of the cost of pap smears and HPV DNA testing versus the country's economic standing, the cumulative cost of co-testing is very high for the average Zimbabwean woman. In addition to costs incurred by patients, studies have also highlighted that in LMICs Page number not for citation purposes 5 only about two thirds of women are interested in and follow up their pap smear results [58][59][60]. Since pap smears are not point of care tests and the follow-up for results can be very poor, it would be very difficult to advocate for resource-constrained governments to subsidise funds for these tests. However, through public participation, an interest to follow up on results can be enhanced as a first step in the awareness campaign. The VIAC is the most commonly used screening method in Zimbabwe [61]. It has a fast turnaround time of approximately five minutes and is an easy method that can be carried out by nurses [62]. In the private sector VIACs are affordable (Table 3), while in public hospitals they are free. VIACs are therefore a favourable alternative in a setting that has technical, infrastructure and financial limitations [56]. VIAC has higher sensitivity than the conventional pap smear and so is more successful in settings were rescreening is unlikely [63][64][65]. In addition, VIACs do not require second opinions for result interpretation or secondary visits for result collection [66]. In India, a similar LMIC, a single round of VIAC decreased the morbidity and mortality of cervical cancer by 25% and 35% respectively after a 7 year period [67]. Moreover, because VIAC has a rapid turnaround time, treatment can be conducted in the same visit in the "screen  (Figure 2). Here patients are treated using cryotherapy and loop electrosurgical excision procedure (LEEP). Overall cure rate of LEEP (96.4%) is higher compared to cryotherapy (88.3%), therefore both are viable treatment options for low-/high-grade CIN [75]. Cryotherapy effectively prevents future development of cervical disease, even in HPV-positive women therefore, it is recommended for screened HPV-positive women without confirmation of disease [76]. However in resource-scarce settings such as rural areas cryotherapy is favoured over LEEP. The success of LEEP depends on various factors, however HIV-positive women have an 86% success rate versus 100% in HIV negative women [77]. A challenge faced with the use of LEEP is overtreatment as a result of difficulty in classifying CIN, which may result in reproductive health challenges [78]. Therefore to avoid overtreatment, it is recommended that LEEP especially in the "screen and treat" is administered by experienced colposcopists with the ability to accurately classify cervical intraepithelial neoplasia and prescribe effective doses. The colposcopy clinics in Zimbabwe are equipped with resources to treat precancerous lesions however there is a challenge with shortage of manpower. In some instances there are a lot of patients that need attention, overwhelming the healthcare workers and resulting in a slow service. Should the initiative to advocate for screening be pushed, the volumes at the colposcopy clinics would increase and this would demand more manpower as well as more colposcopy clinics around the country.
Advanced CIN can be managed surgically in women past child bearing age and with co-morbidities such as uterine fibroids. A common surgical approach, hysterectomy is used for treatment.
Early stage cervical cancer, is treated using a hysterectomy, removal of the cervix and surrounding lymph nodes. The treatment of invasive cervical cancer ranges from radiotherapy and chemotherapy-which are administered dependent on tumour staging, patient performance status and age. As cervical cancer progresses, treatment is chemoradiation for curative purposes. Due to lack of screening, most women in Zimbabwe are diagnosed with cervical cancer at advanced stage (IIb-IIIb) which has a prognosis of 63% 5-year survival rate, 57% remission rate with treatment and 42% recurrence [79][80][81]. Therefore the treatment administered is chemoradiation using cisplatin. There are various private cancer care centres around the country, however most patients seek treatment in the public sector at the two state-owned facilities, the PGH Radiotherapy and Chemotherapy Centre and Mpilo Central Hospital (Figure 2). The cancer treatment centres are equipped with simulators that can be used for 3D radiotherapy [82].
While this machinery provides for improved therapy, it also requires rigorous and frequent maintenance by skilled technicians. A major limitation experienced in state-owned facilities is maintaining Page number not for citation purposes 6 equipment, infrastructure and consumables stock resulting in inconsistent service delivery. Local pharmaceutical companies do not manufacture chemotherapy drugs such as cisplatin [82]. As a result, access to these drugs can be erratic at times. Thus the lack of availability of drugs can decrease chances of successful therapy.
Furthermore the general rate of compliance to prescribed medication and regimes is low due to non-adherence by some patients caused by financial hardships, religious or cultural beliefs.
Given the high incidence of cervical cancer and associated mortality in Zimbabwe, there is need to increase specialists such as nurses, radiographers, medical biophysicists and oncologists. This is not going to happen overnight because Zimbabwe is a low income country thus continues to lose specialists (brain-drain) due to low levels of remuneration when compared to compatriots in other parts of the world. In addition, public cancer treatment centres for the whole of Zimbabwe, are found only in two cities, meaning that many of the patients need to travel long distances to access care.
More so, anticancer therapy requires frequent hospital visits which can span from weeks to months for complete treatment. So transportation for patients to travel is also a major factor that affects compliance to treatment and treatment outcomes. Island Hospice and Healthcare. These hospices offer non-fee paying palliative care in-hospital or at home. At these hospices, families are taught to manage and care for cancer patients, and as well provide support to the affected families by offering counselling [83]. While these hospices are available, knowledge concerning the role of these hospices is very minimal and should be made more available to those in need. This includes the use of media to advertise, as well as more assertive use of social media to disseminate the importance of having such support structures.

Conclusion
Cervical cancer is one of the deadliest diseases in low income countries such as Zimbabwe, even though it is preventable. Routine Moreover, personalizing therapy is also very economical in that patients only receive therapy they would benefit from. Furthermore, implementing educational and awareness campaigns across the country with a primary focus on high risk areas such as rural areas and high risk women such as sex workers should cultivate a health seeking behavior. While developing these educational tools there is a growing need to address cultural and socioeconomic factors that mitigate public health awareness.
What is known about this topic  Cervical cancer is a preventable disease. The burden has been decreased by providing free access to preventive measures such HPV vaccine and screening.

What this study adds
Page number not for citation purposes 7  This study highlights the gaps in the cervical cancer management in Zimbabwe;  There is need for financial resources to be mobilized towards increasing the accessibility of cervical cancer prevention and screening;  The cancer treatment facilities need to be decentralized into hospitals across the country for better coverage.

Competing interests
All authors declare no competing interests.

Acknowledgments
The organization for women in science for the developing world postgraduate fellowship program for providing funds towards this research.    Of 514 participants, 91% had not been screened for cervical cancer; 81% did not know about cervical cancer screening; 80 % were interested in screening after education intervention HPV DNA testing was examined as a mode of screening however low specificity thus need for co-screening.

Treatment
Single visit approach of VIAC followed by LEEP or cryotherapy is feasible and safe Most cervical cancer patients present late, not qualifying for surgery or radiotherapy Chemoradiation is most common form of treatment administered