This is a phase III randomised clinical trial. The aim is to investigate the clinical effects of the addition of modulated electro-hyperthermia (mEHT) to standard treatment protocols (chemoradiotherapy, CRT) for Human Immunodeficiency Virus (HIV) positive and negative locally advanced cervical cancer patients (LACC). SAMPLE: The investigators aim to enrol 236 HIV negative and HIV positive women with LACC, FIGO (Fédération Internationale de Gynécologie et d'Obstétrique) Stages IIB (distil) to stage III. Participants will be randomly assigned to a control group (N=118) and a study group (N=118). METHODOLOGY: Randomisation is based on age, stage and HIV. Participants from both groups will receive the standard treatment for cervical cancer at the hospital at the Charlotte Maxeke Johannesburg Academic Hospital in South Africa: Up to three doses of 80mg/m2 cisplatin, administered three weeks apart; 50Gy external beam radiation (EBR) in fractions of 2Gy; Three doses of 8Gy High Dose Rate (HDR) brachytherapy. The study group will have two 55 minute mEHT treatments per week, at 130W, directly before the EBR using the EHY 2000 Device. OUTCOMES: 1) Determine the local disease control after treatment at 6 months using a Positron Emission Tomography (PET) and computerised tomography (CT) scans. 2) Determine the progression-free survival (PFS) at 6, 12, 18 and 24 months after the last treatment date. PFS will be assessed in all registered participants, regardless of completion (Intent to Treat-ITT) as well as only in the subset of participants who complete the prescribed CRT. 3) Overall survival at two years will be assessed. 4) To evaluate the adverse events associated with mEHT. 5) The effect of mEHT on chemotherapy and radiotherapy tolerability and toxicity will be evaluated. 6) The quality of life of enrolled participants will be assessed before, at 6 weeks, and at 3, 6, 9, 12, 18 and 24 months after completion of therapy using the EORTC (European Organisation for Research and Treatment of Cancer) and EuroQoL forms. 7) To evaluate the economic viability of the addition of mEHT to standard treatment protocols for LACC. 8) The effect, if any, of mEHT treatments on the HIV disease status of HIV positive patients will be assessed by the presence of Autoimmune Deficiency Syndrome (AIDS) defining illnesses before and after treatment. 9) The cancer recurrence patterns will be described and compared in all the participants.

Inclusion Criteria:

1. Participants (who have been adequately clinically staged by standard clinical guidelines) with biopsy proven primary, untreated, histologically confirmed invasive squamous and aden-squamous cell carcinoma of the uterine cervix, FIGO (Fédération Internationale de Gynécologie et d'Obstétrique) stages advanced IIB (invasion of the distal half of the parametrium), IIIA and IIIB.

2. HIV positive participants will be accepted.

3. The following laboratory tests will be done prior to enrolment in the study and the values must be in the following ranges:

   • Haemoglobin >10 g/dL;
   • Platelet count >150/mm3;
   • Absolute neutrophil count (ANC) >3000/mm3
   • Creatinine clearance>60 mL/min
   • Liver function tests

4. Females between the ages of 18 and 70 years.

5. Ability to understand and the willingness to sign a written informed consent document.

6. Eastern Cooperative Oncology Group (ECOG) score of not more than 2.

7. Participants of childbearing potential must have a negative urine or serum pregnancy test prior to enrolment and use an effective form of contraception (e.g. barrier contraception, highly effective hormonal contraception).

8. At the investigators' discretion, participants must be suitable for treatment with radical intent using concurrent chemotherapy and pelvic radiation. Subjects who undergo emergency RT in the form of brachytherapy for haemostasis, prior to enrolment will be allowed to be screened and enrolled provided they meet all other eligibility criteria.

9. Life expectancy of greater than 12 months.

10. Participants must have a body mass index (BMI) that is within normal ranges.

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Exclusion Criteria:

1. Participants who have undergone hysterectomy.

2. Exclude para-aortic lymph involvement on planning CT (without contrast)

3. Patients with life-threatening AIDS defining illnesses (other than cervical carcinoma) will be excluded, as will patients with a CD4 count < 200/µL and not on ARVs.

4. Patients with acute active (such as tuberculosis or malaria), serious, uncontrolled infections will be excluded.

5. Participants will be excluded if there is evidence of resistance to antiretroviral therapy (i.e. HIV viral load > 400 copies/mL despite combination antiretroviral therapy for at least 4 months).

6. Prior invasive malignancy other than cervical cancer, diagnosed within the past 24 months, excluding in situ anal dysplasia or carcinoma in situ, non-melanoma skin carcinoma, or Kaposi's sarcoma that has not required systemic chemotherapy within the past 24 months.

7. Pregnant or breast-feeding women.

8. A medical or psychiatric illness that prevents the participant from being able to sign an informed consent or would affect the participant's ability to comply with the protocol stipulations.

9. Participants with circumstances that will not permit completion of the study or required follow-ups. For instance if travel to and from treatment site is an issue.

10. Participants with carcinoma of the cervical stump.

11. Participants with a history of cardiovascular disease manifested as

    1. History of myocardial infarction
    2. Unstable angina
    3. Currently taking medication for treatment of angina
    4. History of coronary artery bypass surgery

12. Participants with contraindications to modulated electro-hyperthermia treatment:

    1. Pace makers and other implanted devices which rely on current and charges.
    2. Large metal implants, such as hip replacements.
    3. Inability to feel temperature in the region.
    4. Inability to express or vocalise discomfort or heat at the treatment site.

Clinicians conducting follow up evaluations, radiographers and nuclear medicine physicians reporting on the PET/CT investigations are unaware of the group that the participants have been assigned to.