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 Table of Contents  
CASE REPORT
Year : 2016  |  Volume : 6  |  Issue : 4  |  Page : 219-223

Optimum management of invasive cervical cancer in HIV/AIDS patients and impact on survival: Case series from a resource-limited setting and literature review


1 Radiotherapy and Oncology Centre, ABU Teaching Hospital, Zaria, Nigeria
2 Oncology Unit, Rasheed Sekoni Specialist Hospital, Dutse, Jigawa State, Nigeria

Date of Web Publication8-Dec-2017

Correspondence Address:
Dr. A Adamu
Radiotherapy and Oncology Centre, ABU Teaching Hospital, Zaria
Nigeria
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/ais.ais_4_17

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  Abstract 

With the lengthening of life expectancy among HIV-positive subjects related to the use of highly active antiretroviral (HAART) treatments, an increased risk of cancer has been reported in this group of patients. The clinical management of cancers, including cervical cancer in HIV-positive patients has challenges mainly due to the concerns on immune status. At present, their mode of management is similar to HIV-seronegative patients and involves the use of chemotherapy and radiotherapy concurrently, as indicated. This becomes more challenging because HIV infection, cancer, radiotherapy, and chemotherapy lower immunity through reduction in CD4 cell counts, which is further complicated with low-resource setting of late presentation, poor access to HAART, lack of accessible radiotherapy facilities, and poverty.

Keywords: Cervical cancer, HIV/AIDS, survival


How to cite this article:
Adamu A, Dawotola D A, Mohammed I M, Olasinde T A. Optimum management of invasive cervical cancer in HIV/AIDS patients and impact on survival: Case series from a resource-limited setting and literature review. Arch Int Surg 2016;6:219-23

How to cite this URL:
Adamu A, Dawotola D A, Mohammed I M, Olasinde T A. Optimum management of invasive cervical cancer in HIV/AIDS patients and impact on survival: Case series from a resource-limited setting and literature review. Arch Int Surg [serial online] 2016 [cited 2019 Oct 19];6:219-23. Available from: http://www.archintsurg.org/text.asp?2016/6/4/219/220327


  Introduction Top


Cervical cancer is one of the most common neoplastic diseases affecting women, with a combined worldwide incidence of almost half a million new cases annually, second only to breast cancer.[1] In Nigeria, it accounts for about 30.8% of all female malignancies.[2] Human Immunodeficiency Virus (HIV) infection has been strongly associated with carcinoma of the cervix, which has been classified as one of the AIDS-defining malignancies.[3] According to a report, sero-prevalence of HIV amongst adults aged 15 years to 49 years in Nigeria was 3.1 (95% CI, 2.3–3.8%) with significant regional variations.[4] A study in Ibadan, Nigeria, showed that about 2.7% of patients with cervical cancer were found to be seropositive.[5] This sharply contrasts to findings in Johannesburg, South Africa, which showed a very high association of HIV with cervical cancer.[6],[7]

Overall, the risk of malignancy is doubled in an HIV-infected population, with reported cases in the literature suggesting that invasive cervical cancer in HIV-infected individuals is often of a highly aggressive and advanced nature, with poor response to treatment, rapid recurrence, and metastases to unusual sites. Consequently, there is a rapid mortality among these group of patients when compared to non-HIV infected cervical cancer patients.[8],[9] In general, in populations where treatment for HIV/AIDS with Highly Active Anti-Retroviral Therapy (HAART) is available, individuals with HIV are found to be living longer and in relatively good health with the disease. In such populations, HIV/AIDS-related malignancies, of which cervical cancer is an example, have become the single most important cause of morbidity and mortality.[10] Therefore, in this group of patients, treatment may become difficult due to altered sensitivity to side-effects of HAART, chemotherapy, and radiotherapy.[11]

We describe our experience with four histologically confirmed cervical cancer patients with HIV/AIDS who achieved significant disease-free survival after initiation of treatment.


  Case History Top


Patient 1

A.H was a 34-year-old para(p)4+2 woman who presented to the Oncology Clinic with a four-month history of post-coital bleeding and two-month history of inter-menstrual bleeding with associated copious foul smelling vaginal discharge, abdominal and waist pain. She was the second of three wives of the husband. She was found to be ill-looking but well preserved with a Karnofsky Performance Score (KPS) of 80%. Significant findings on pelvic examination was an exophytic cervical mass, which bled readily to contact. Parametrial and pelvic side walls were free of disease. An ultrasonography of the abdomen and pelvis revealed a cervix mass of about 8 × 5 cm in dimension. Histopathology report confirmed moderately differentiated squamous cell carcinoma. The patient was seropositive to HIV-1 antibodies and had been on HAART for about 5 years. The CD4 count on presentation was 348 cells/μl. Her hemogram, blood chemistry, and liver function tests were essentially within normal range. She was clinically staged IIA using the International Federation of Gynecologists and Obstetricians (FIGO) criteria. She received three courses of chemotherapy, which consisted of cisplatin at 50 mg/m 2 and 5-fluorouracil at 500 mg/m 2 administered three weekly for three courses (as neo-adjuvant chemotherapy). This was followed by external beam radiotherapy (EBRT) to the pelvis using a parallel-opposed AP/PA fields on a telecobalt machine. A total dose of 45Grays (Gy) in 25 fractions was given over 5 weeks. She was, however, placed on a weekly cisplatin (40 mg/m 2) during the EBRT. Two weeks after the completion of EBRT, she had a brachytherapy with the aid of a remote after-loading low dose rate Ceasium-137 machine. A dose of 30Gy was administered to Manchester point A (using dedicated Fletchers applicators reserved for HIV-infected individuals with gynecologic cancers). Patient did excellently well and survived 5 years with no evidence of a local recurrence or distant metastasis. She however succumbed to an overwhelming pulmonary tuberculosis at 5 years 3 months from the date of first presentation at the Oncology Clinic.

Patient 2

J.A was a 29-year-old para(p)2+3 woman who presented to the oncology clinic with an 8-month history of foul smelling vaginal discharge, a 6 months history of polymenorrhea and intermenstrual bleeding. There was associated low back pain and severe suprapubic discomfort of about three months duration. She was the only wife of her husband, a banker who had died a year earlier from an undisclosed ailment. Patient appeared well preserved, with a KPS of 70%. Ultrasonography revealed cervical mass measuring 9 × 6 cm. She was seropositive for HIV-2 and had been on HAART for 6 years. Her presenting CD4 count was 180 cells/μl. Examination under anesthesia revealed bulky and friable cervical mass with pelvic side wall affectation and she was staged as FIGO IIIB. She was offered EBRT to the pelvis and received 45Gy in 25 fractions over 5 weeks on a telecobalt machine concurrently with weekly cisplatin at 40 mg/m 2. This was followed two weeks later by intracavitary brachytherapy, using LDR remote after-loading Ceasium-137 machine. A dose of 25Gy was administered to Manchester point A. The patient did excellently well and during her last follow up visit 4 years and 8 months' post treatment, there was no clinical or radiologic evidence of local disease recurrence or distant metastasis. She reportedly died in a road traffic accident not long after the visit.

Patient 3

S.Y was a 32-year-old para(p)5+0 woman who presented to the Oncology outpatient clinic with profuse vaginal bleeding of three day's duration, post coital bleeding of three-month duration, intermenstrual bleeding of 5 months' duration. There was associated foul-smelling vaginal discharge. She also complained of low back and suprapubic pains. She was the only wife of a long-distance driver. She was seropositive to HIV-1 and 2 antibodies and had been on HAART 7 years previously. She had pallor of moderate severity and her KPS was 50%. Ultrasound abdomen and pelvis confirmed bulky cervical disease measuring 10 × 8cm. Examination under anaesthesia revealed bulky and friable exophytic cervix tumor with pelvis side wall affectation and was staged FIGO IIIB and histopathology confirmed poorly differentiated non-keratinizing squamous cell carcinoma. The anemia was corrected with appropriate blood transfusion. She also had hemostatic EBRT 10Gy in 3 fractions over three days. This was followed by 32Gy in 18 fractions given over 3.5 weeks on the telecobalt machine. Three weeks later she had an intracavitary Ceasium-137 brachytherapy with the aid of a vaginal cylinder on the LDR remote after-loading brachytherapy machine. She received a dose of 20Gy at 0.5 cm depth of the vaginal cylinder surface. The patient was alive and well 17 months after treatment but was soon lost to follow up and presumed dead.

Patient 4

T.K was a 40-year-old para(p)6+1 who presented to the Oncology outpatient clinic with two day's history of profuse vaginal bleeding, intermenstrual bleeding of 5 months' duration with associated foul smelling vaginal discharge. She also complained of low back pain and difficulty in defecation. She is the second wife of her husband's three wives. Abdominal and pelvic ultrasonography scan revealed 11 × 8 cm cervical mass. Examination under anesthesia revealed an exophytic, friable, and bulky cervical tumor with pelvis side wall affectation and was staged FIGO IIIB. Histopathology of biopsy specimen confirmed poorly differentiated squamous cell carcinoma. She was confirmed as seropositive to HIV-1 antibodies and had already been on HAART for 4 years. Her presenting CD4 count was 48 cells/μl and she had a KPS of 40%. Anemia was corrected with appropriate blood transfusion. She received hemostatic EBRT 9Gy in three alternate day fractions over five days, followed three weeks later by further EBRT with 3Gy per week for four times and died after 9 months from time of initial presentation.


  Discussion Top


The clinical management of cancers, including invasive cervical cancer in HIV/AIDS patients has huge challenges, which are mainly due to the concerns of immune status. Various studies have shown that HIV-infected patients have impaired marrow function as well as impaired cellular immunity, thus making them more vulnerable to the effects of anti-cancer treatments.[12] In addition, their nutritional and physical status may be impaired and this will further limit their ability to withstand cancer therapy. Many of the drugs, such as AZT (zidovudine), used to treat the HIV virus are mostly myelo-suppressive in nature, thereby making it difficult to utilize effectively all available cancer treatment modalities, such as external beam radiotherapy,[13] brachytherapy, and chemotherapy.[14]

The median age of the patients presented in this report is 33.75 years, which was a decade and a half lower than that of non-HIV cervix cancer patients [15] (33.75 years vs. 48 years). This finding can be attributed to the fact that high virulence and rapid progression of HPV infection in causing invasive cervical cancer are observed more in HIV-positive patients than HIV-negatives and the predominant histological cell type seen in the patients in this report was squamous cell carcinoma and this is not different from what is encountered in HIV-negative patients.[16]

Similarly, all the patients in this report presented with advanced stage of disease (FIGO stage IIB and above), which is consistent with the reports in the literature by Maiman et al.[17] stating that patients who tested HIV positive usually have more advanced cervical cancer than HIV-negative patients. This may be due to the fact that areas with high incidence of cervical cancer are mostly in the resource-limited settings where access to screening and early treatment of the disease is low and therefore majority of the patients with cervical cancer present late, irrespective of HIV status.[18],[19],[20]

Commencement and or continuation of HAART sequentially or concurrently with chemoradiation therapy in HIV-positive cervical cancer patients had been controversial with several reports in the literature in favor of or against the use of HAART in HIV/AIDS. There is the belief that patients on HAART are likely to complete and tolerate the treatment better with less incidence of the HIV virus developing resistance than those who are not.[21] Similarly, it has been found that HIV patients on chemotherapy have increased viral load if not on HAART and the viral load decreases as soon as HAART is introduced.[22] On the contrary, there are opinions that introduction of HAART may potentiate treatment toxicity.[23] In our opinion, allowing the patients in this report to continue on HAART might explain the excellent response to treatment that they exhibited with manageable toxicity.

Though at present, optimal uniform treatment modalities for cervical cancer in HIV/AIDS patients are yet to be established, our patients were offered full treatment with EBRT, brachytherapy, and chemotherapy like in their non-HIV infected counterparts, with the aim of achieving maximal disease control. Those with good performance status above 60% (patients 1–3) received radical doses of radiotherapy. Reports in the literature have shown that curative dose of EBRT can be offered to immune-compromised patient with a good performance status in spite of low CD4 counts.[21] The use of CD4 counts as criteria for commencement of HAART and other management interventions in HIV/AIDS patients with invasive cervical cancer has remained debatable. Some studies used CD4 counts of 200 as the minimum level to commence HAART,[24] while another study reported a CD4 count of ≤350 as the minimum level for commencement of HAART, which is the current WHO recommendation for ordinary HIV-positive patients.[25] According to the literature, concurrent chemoradiation therapy is the gold-standard in treatment of invasive cervical cancer in normal non-HIV infected cancer patients due to better disease control and improvement in overall survival.[26],[27] A meta-analysis report showed absolute benefit in using radiotherapy and concurrent chemo-radiotherapy in the management of cervical cancer. In this report, fifteen trials were analyzed and it was found that there was an absolute benefit of 6% with chemo-radiotherapy over radiotherapy alone in disease-free survival and 8% benefit in disease control over 5 years. The effect was, however, found to be greater in early disease than with advanced disease. The absolute survival benefits were 10% (Stage IA to IIA), 7% (Stage IIB), and 3% (Stage III to IVA) at 5 years.[28]

Generally, survival in HIV/AIDS patients with invasive cervical cancer is poor. A study in South Africa [7] reported an average survival of just 10 months. Other studies reported survivals of up to 24 months.[24] One-year survival of 80.6% and 5-year survival of 2.4% were reported in one Italian study. In another Italian population-based study, 2-year and 5-year survivals were 75.2% and 66.4%, respectively.[26] According to the literature, the 5-year survival rate for HIV-negative women with stages IA/IB cancer of the cervix is over 90%, while women with stages IIIA/IIIB, may have a 5-year survival rate of more than 50%.[27]

The patients reported in cases 1 to 4 survived 5 years 3 months, 4 years 8 months, 13 months, and 9 months, respectively, indicating that disease burden, FIGO stage, CD4 count at presentation, use of HAART, and performance status all play a vital role in the outcome of patients treated with chemoradiation therapy in HIV-positive patients with cervical cancer.


  Conclusions Top


Radical chemoradiation in conventional doses may be safely tolerated by a well-selected cervical cancer HIV-positive group on HAART and could be considered suitable for similar patients. Therapeutic strategies that address the dismal survival in this group of patients might be explored and developed. Palliative fractionation radiotherapy schedules (sometimes with curative intent) are effective for patients with poor performance status and locally advanced cancers in relieving the symptoms related to carcinoma cervix. More research is therefore required to determine what these strategies are. Cancer prevention and screening should therefore be rigorously implemented to allow for early detection and prompt institution of appropriate management, particularly in HIV/AIDS patients.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

 
  References Top

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