This study is the first study to evaluate treatment completion following referral from a VIA screening program for invasive cervical cancer. Our results show a high proportion of women referred from the screening clinic followed up and completed treatment for their cancer at ORCI. We estimate at least 76% of women diagnosed with invasive disease at the ORCI screening clinic received at least some treatment, and at least 70% completed their prescribed radiation. These proportions are likely higher, were we to account for treatment received elsewhere.
Lower disease stage, having a skilled occupation, residence in Dar es Salaam, and younger age were independently associated with loss to follow-up. Higher disease stage, residence in Dar es Salaam, older age, and later year of first treatment appointment were independently associated with incomplete treatment among those who followed up. Significantly more screened women had stage 1 disease (14.0%) than unscreened women (7.8%). In most cases, the screening clinic appears to facilitate diagnosis and treatment, rather than screening, for women with invasive cervical cancer.
We found that more advanced disease stage was associated with greater likelihood of follow-up. However, women with more advanced disease stage were less likely to complete their prescribed radiation. The south Indian trial suggested invasive cancer (all stages combined) was associated with a greater likelihood of treatment completion compared to low grade, pre-cancerous lesions (OR = 1.55, 95% CI 0.7-3.6) [15], but this is not directly comparable to our study because we did not include women with pre-cancerous lesions. Furthermore, the south Indian trial did not separately assess follow-up and treatment completion among those who followed up, as in our study.
Some of those lost to follow-up likely received treatment elsewhere. Women with skilled occupations were half as likely to follow up for treatment as housewives or manual laborers. This likely reflects that women with higher socioeconomic status have the means to travel outside of Tanzania for cancer treatment, typically to Kenya, South Africa, or India. Occupation was not, however, associated with completion of radiation among those who did follow up at ORCI. This finding suggests finances were not a significant barrier to treatment, which is government funded and provided free of charge in Tanzania. The south Indian trial also found occupation was not associated with compliance to treatment, which was free of charge [15].
ORCI is the only specialized cancer treatment center in Tanzania, so it attracts patients from every region of the country. Nearly half of women with invasive disease were from outside of Dar es Salaam, and they were more likely to both follow up and complete treatment compared to women residing in Dar es Salaam. Residents of other regions also presented for follow-up sooner than women from Dar es Salaam and were less likely to have stage 1 disease. The reasons for these differences by region should be explored in future studies.
Older women were more likely to follow up, but were less likely to complete radiation therapy, although these associations were not significant in multivariable analysis. The effect on follow-up appears to be driven by loss to follow-up among the youngest patients, while the effect on radiation appears to be driven by incomplete treatment among the oldest patients (results not shown).
Although the proportion of women who followed up did not change significantly over the study period, the data suggest that the proportion of women completing radiation decreased over time. The volume of patients (all cancers) increased 64% over the study period, from 1,897 in 2002 to 3,102 in 2011, placing an increased burden on radiation therapy equipment, which sometimes broke down. Scheduling radiation therapy also became increasingly difficult, since many patients required 15 to 20 sessions to complete their prescribed dose. The increased patient volume may also account for the increase in follow-up time seen over the study period, since follow-up time is a function of both provider (supply) and patient (demand) factors.
The assessment of treatment focused on radiation because it was most consistently documented and is the primary cervical cancer treatment modality at ORCI. However, for patients treated with curative intent, radiation is supplemented by brachytherapy when the machine is operable, and chemotherapy in some cases. Only women who completed their prescribed radiation went on to receive brachytherapy, per ORCI guidelines. Less than one-fifth of women received at least one dose of chemotherapy, and this was often for palliation.
The proportion of screened women diagnosed with invasive cancer (4.9%) was higher than reported in other African studies (3.5% in Mali [11], 1.9% in Zambia [9], and 0.6% in Angola [13]). This difference likely reflects both the high burden of cervical cancer in Tanzania, as well as the program design. While the absolute number of cervical cancer cases referred from the screening clinic each year did double from 2003-2010, the increasing proportion of women diagnosed with invasive disease was also a function of significant changes in the number attending the screening clinic over time. Initially, considerable efforts were taken to recruit women from the community for screening [12], with 4,758 women screened during the first full year of the program (2003). The lowest proportion of invasive disease was seen in that year, since many of the women screened would not have attended unless invited. In contrast, women with invasive cervical cancer or another gynecologic problem are typically symptomatic and more likely to attend the screening clinic uninvited. These women represented a larger proportion of screened women in later years, when there were fewer screening promotion efforts in the community.
It is clear that women with symptomatic cervical cancer are attending the ORCI screening clinic seeking a proper diagnosis, rather than screening. They have often been treated for symptoms of cervical cancer at the regional and local level, delaying a formal diagnosis and initiation of appropriate therapy in many cases. In this study, all women who followed up were symptomatic, and a quarter of women who followed up had already been seen elsewhere. ORCI’s VIA screening program has directly contributed to development of the human capital and clinic infrastructure necessary for not only VIA screening, but also for providing basic gynecologic care and referral. With these resources, women can be efficiently directed to appropriate care.
Screening also resulted in a higher likelihood of diagnosis with stage 1 disease, compared to unscreened women treated at the same institution. This downstaging suggests the ORCI screening program is not only facilitating diagnosis for women with more advanced, symptomatic disease, but also detection for women with earlier stage, less symptomatic or asymptomatic disease. This may be the case for some of the 32 women with stage 1 disease who were lost to follow-up.
A limitation of the study was the lack of a common identification number used throughout all records, potentially leading to missed cases in our analysis. Although a screening clinic serial number partially filled this purpose, it was not always used in patient records and was not included in patient log books. Referrals from screening to treatment were not formally tracked, so a case definition had to be established based on available data that may have misclassified some screened women. Since we only reviewed treatment records at ORCI, we could not account for the small proportion of women who may have been treated at institutions in other countries. Finally, these results may not be generalizable to screening programs operated distant from cervical cancer treatment services.
An important strength of this study is the inclusion of 980 cases of cervical cancer referred from a VIA screening program over an 8.5 year period, nearly twice the number of women included in the next largest study [11]. This sample size permitted evaluation of follow-up and treatment completion across the diverse demographics served by the screening clinic, with a wide range of occupations, education levels, and ages represented. Additionally, most patient and disease characteristics were measured before follow-up and treatment. This is the first study to differentiate between follow-up and treatment completion and we have demonstrated that the factors associated with these outcomes appear to differ.
Future studies could investigate what proportion of women diagnosed with invasive cervical cancer at ORCI screening receives treatment elsewhere. In addition, research using patient interviews could help explain the patterns of follow-up and treatment completion seen in this study.