HIV infected individuals are at an increased risk of developing cancer. 13 In the early 1980’s, reports of a cluster of cases of Pneumocystis jiroveci and an unusually aggressive malignancy, Kaposi’s sarcoma in homosexual men drew attention to the rising AIDS pandemic. It soon spread throughout the globe and soon worldwide, there were increasing reports of certain specific cancers namely Kaposi’s sarcoma, aggressive lymphomas and cervical cancers, which have now been termed as AIDS defining cancers. The discovery of Kaposi Sarcoma Herpes viruses that was responsible for development of Kaposi’s sarcoma, led to the understanding of the oncogenic potential of other viruses including the Epstein Barr virus and Human Papilloma viruses. 9
The present study included 627 HIV infected patients which included 50 cases of patients with HIV and malignancy. The majority of the patients were male and the mean age was 42.9 years. In a study by Venkatesh et al, the authors studied 42 patients with HIV and malignancy, in which majority of the patients were male. The mean age of the patients in the study was 35 years. These findings were similar to the present study. 11
The prevalence of malignancies in patients with HIV in the present study was found to be 8%. In a study done in Guinea, Traore et al. studied 2598 patients with cancer which included 54 patients with HIV and found a high prevalence of HIV (2.1%). They estimated that 30–40% of HIV patients are at a risk of developing malignancies.
Of the 50 patients, details of the CD4 cell count at time of diagnosis of malignancy was available in 29 patients. The mean CD4 cell count at the time of diagnosis with malignancy was 502.45/uL. Among these, 4 patients (13.8%) had a CD4 cell count of < 50/Ul and 3 patients (10.3%) had a CD4 cell count of 400–450/uL.
In a study by Monforte et al. the researchers reported that lower CD4 cell counts were associated with higher mortality. They found that doubling the CD4 count led to a reduction in mortality to approximately half. Even among patients who received ART, the latest CD4 cell count as well as the nadir CD4 cell counts were independent predictors of mortality in HIV patients with AIDS defining malignancies. 14
Other researchers have also similarly described the association of lower CD4 cell counts with risk of malignancy particularly for infection related cancers including Hodgkin lymphoma, cervical carcinomas, hepatocellular carcinomas and anal carcinomas. 15
In a study by Clifford et al. the authors followed 7304 HIV patient records from the Swiss HIV Cohort Study and Swiss cantonal cancer registries. They reported that the standardized incident ratio for Kaposi’s sarcoma and Non-Hodgkin’s lymphoma had an inverse association with CD4 cell counts. However, this association was not observed for other malignancies including cervical carcinomas, for cancers of the lip, mouth, pharynx, trachea, lung, brochus and non-melanomatous skin cancer. They concluded that patients who were on ART had a lower risk of Kaposi’s sarcoma as well as Non-Hodgkin lymphoma. However, the benefit of ART therapy did not reduced risk of development of Hodgkin’s lymphoma and other non-AIDS defining malignancies. 16
In the present series, majority of the patients (72%) had a non-AIDS defining malignancies similar to the finding by Traore et al 25. The cases in the present study included malignancies of the oral cavity, nasopharynx, larynx, female genital tract, haematolymphoid malignancies, lung, GIT including anal canal, breast carcinoma, male genital tract, eye, urinary tract and metastatic lesion with an unknown primary.
HIV infected individuals have a two to four times higher risk of head and neck carcinomas and double the risk of oral cavity and pharyngeal carcinomas as cancer compared to HIV un-infected individuals. This may be attributable to HPV with studies showing a prevalence of oncogenic HPV ranging from 12–26% among HIV infected individuals. Of the various subtypes, HPV 16 has been implicated in over 80% of malignancies of the oropharynx.24
There were 3 cases each of anal carcinomas, cervical carcinomas, multiple myelomas, lung and GIT excluding the anus.
In a study done in Guinea, authors reported that breast cancer was the most common non-AIDS defining malignancy, while lung malignancy was more common in developed countries, in contrast to the present study, where we found a lower incidence of both these malignancies. In another study by Venkatesh et al, the researchers found Hodgkin’s lymphoma to be the most frequent malignancy among the non-AIDS defining malignancies, followed by breast carcinomas(11).
The AIDS defining malignancies accounted for only a minority of cases in the present study (28%). Among these, the most common was NHL, followed by cervical cancers. These findings were similar to that reported by Venkatesh et al and Traore et al(11,25).
There were no reported cases of Kaposi’s sarcoma in the present study. This was similar to findings reported by Phatak et al. The authors noted that AIDS defining cancers including Non-Hodgkin lymphoma and cervical carcinomas, were seen in 54.35% cases whereas non-AIDS defining cancers were noted in 45.65% cases. The authors too did observe Kaposi’s sarcoma in their study. This was in contrast to another study from Nigeria that have found increased risk of development of Kaposi’s sarcoma but neither Non-Hodgkin lymphoma or cervical carcinomas among HIV infected patients. This highlights significant demographic differences with respect to malignancies among HIV infected individuals in different parts of the world. 17,18
Among the malignancies, 16 patients (32%) had HPV linked malignancies, while 34 patients (68%) had non-HPV linked malignancies. Studies have reported a high incidence and prevalence of association of HPV as well as precursor lesions in patients with HIV as compared to the general population. These includes ano-genital malignancies including cervical carcinomas and anal carcinomas. Authors have reported that the risk of anal carcinomas is higher in homosexual men and have recommended screening the at-risk population. Similarly, current guidelines for HIV infected women recommend cytology screening once in every six months for 2 consecutive negative cytology results and thereafter yearly. Researchers have recommended colposcopic examination with acetic acid for cervical carcinoma screening in resource strapped countries to reduce the incidence of these cancers(26).
The risk of HPV related malignancies at other sites including oropharynx, penis, vulva, vagina have also been predicted to be increased although at present, data is limited with regard to these. 19,20
Presently, cancer screening plays a crucial role in the routine management of patients living with HIV, which would include an assessment of individual risk, survival, risks and benefits of screening as well as its potential outcome. Although the successful intervention in the form of cancer screening in general population has proved beneficial, data on similar intervention in HIV infected individuals is lacking. Sigal et al. provided a conceptual framework of screening for cancer in patients with HIV. This included a Pap test for cervical carcinomas, anal cytology test for anal carcinomas, abdominal ultrasound and AFP estimation for hepatocellular carcinomas. In addition to these, other screening modalities including mammography for breast carcinoma, fecal occult blood testing and sigmoidoscopy for colonic carcinoma, PSA test for prostatic carcinoma, CT scans in heavy smokers for lung carcinoma have been recommended by other authors. 21
There was 1 case of malignancies in a child and no cases of malignancies in young adults. Researchers have reported highest frequency of Kaposi’s sarcoma, NHL and leiomyosarcoma in the young. However, the child in our study had Non Hodgkins Lymphoma.
Yet another study by Dhokotera et al. studied 1853 cases of adolescent and young patients of HIV with malignancies and found maximal cases of Kaposi sarcoma, cervical carcinoma, Hodgkins lymphoma and anogenital carcinomas other than cervix.
Researchers have documented higher incidence of malignancies caused by oncogenic viruses attributable to high risk behavior in sexually active adolescents and adults such as cervical carcinomas, anogenital carcinomas and hepatocellular carcinomas. There remains a higher risk in those individuals who have perinatally acquired HIV infection, attributable to various factors including longer duration of infection with HIV, immune dysregulation and co-infection with HBV, HCV or both. Thus it is recommended that this unique cohort of young patients must be diagnosed at the earliest and started on ART therapy and that access to HPV and HBV vaccination as well as individualized cancer screening facilities should be provided in their multidisciplinary services. 22,23