Cervical cytological changes in HIV-infected patients attending care and treatment clinic at Muhimbili National Hospital, Dar es Salaam, Tanzania

Abstract

Background: Tanzania is among Sub-Saharan countries mostly affected by the HIV and AIDS pandemic, females being more vulnerable than males. HIV infected women appear to have a higher rate of persistent infection by high risk types of human papillomavirus (HPV) strongly associated with high-grade squamous intraepithelial lesions (HSIL) and invasive cervical carcinoma. Furthermore, although HIV infection and cervical cancer are major public health problems, the frequency and HIV/HPV association of cervical cancer and HSIL is not well documented in Tanzania, thus limiting the development of preventive and therapeutic strategies.

Methods: A prospective unmatched, case-control study of HIV-seropositive, ≥ 18 years of age and consenting non-pregnant patients attending the care and treatment center (CTC) at Muhimbili National Hoospital (MNH) as cases was done between 2005 and 2006. HIV seronegative, non-pregnant and consenting women recruited from the Cervical Cancer Screening unit (CCSU) at ORCI were used as controls while those who did not consent to study participation and/or individuals under < 18 years were excluded. Pap smears were collected for routine cytodiagnosis and P53 immunohistochemistry (IHC). Cervical lesions were classified according to the Modified Bethesda System.

Results: A total of 170 participants from the two centers were recruited including 50 HIV-seronegative controls were from the CCSU. Ages ranged from 20-66 years (mean 40.5 years) for cases and 20-69 years (mean 41.6 years) for controls. The age group 36-45 years was the most affected by HIV (39.2%, n = 47). Cervicitis, squamous intraepithelial lesions (SIL) and carcinoma constituted 28.3% (n = 34), 38.3% (n = 46) and 5.8% (n = 7) respectively among cases, and 28% (n = 14), 34% (n = 17) and 2% (n = 1) for controls, although this was not statistically significant (P-value = 0.61). IHC showed that p53 was not detectable in HPV + Pap smears and cell blocks indicating possible degradation.

Conclusions: The frequency of SIL and carcinoma appeared to be higher among HIV-infected women on HAART compared to seronegative controls and as expected increased with age. HIV seropositive patients appeared to present earlier with SIL compared to those HIV seronegative suggesting a role of HIV in altering the natural history of HPV infection and cervical lesions. The absence of p53 immunoreactivity in HPV + lesions is indicative of the ability of HPV E6 proteins to interact with the tumor suppressor gene and pave way for viral-induced oncogenesis in the studied Tanzanian women.

Figure 1

The distribution of patients according to marital status and HIV infection. Histograms showing the distribution of patients according to marital status and HIV infection.

Figure 2

The distribution of cytological types of cervical carcinoma and HIV status. This Histogram shows that squamous cell carcinoma (SCC) as well as squamous intraepithelial lesions (SIL) were more common amongst HIV seropositive women.

Figure 3

Pap smear showing bacterial vaginosis. A micrograph showing Pap staining showing abundant clue cells (arrow) suggestive of bacteria vaginosis more likely due to Gardnerella vaginalis infection (× 40).

Figure 4

Pap smear showing Chlamydia cervicitis. Pap staining in a patient with acute cervicitis showing a squamous cell with cytopathic changes characterized by the presence of a cytoplasmic inclusion body (arrow and inset) indicating Chlamydia infection (× 40).

Figure 5

Pap smear showing LSIL. Pap staining in a patient with LSIL showing extensive leukocytic background and a binucleated parabasal squamous cell with mild nuclear enlargement and fine granular chromatin (arrow and inset) suggestive of viral (HPV) or TV infection (× 100).

Figure 6

Pap smear showing HSIL. Pap staining in a patient with HSIL showing abundant neutrophils, a cluster of dendritic cells. The arrows show a parabasal squamous cell with multiple cytoplasmic vacuolation suggestive of viral infection (× 40).

Figure 7

Pap smear showing cervical cancer. Pap staining in a patient with squamous carcinoma which exhibits clusters of cohesive cells with marked nuclear enlargement, pleomorphisms, hyperchromatism and keratinization (× 40).