Department of Pathology, Muhimbili University of Health and Allied Sciences (MUHAS), P.O. Box 65001, Dar es Salaam, Tanzania.
Infect Agent Cancer. 2012 Feb 15;7:3. doi: 10.1186/1750-9378-7-3.
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.
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.
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.
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.
坦桑尼亚是撒哈拉以南非洲国家中受 HIV 和艾滋病流行影响最大的国家之一,女性比男性更容易受到影响。感染 HIV 的女性似乎具有持续感染高危型人乳头瘤病毒(HPV)的更高风险,这与高级别鳞状上皮内病变(HSIL)和浸润性宫颈癌密切相关。此外,尽管 HIV 感染和宫颈癌是主要的公共卫生问题,但在坦桑尼亚,宫颈癌和 HSIL 的频率以及与 HIV/HPV 的关联尚未得到很好的记录,这限制了预防和治疗策略的制定。
本研究是一项前瞻性、无匹配、病例对照研究,纳入了 2005 年至 2006 年期间在穆希比利国家医院(MNH)的护理和治疗中心(CTC)就诊的年龄≥18 岁且同意接受检查的 HIV 阳性、非妊娠患者作为病例,并招募了来自 ORCI 的宫颈癌筛查单位(CCSU)的 HIV 阴性、非妊娠且同意参加研究的女性作为对照,而那些不同意参与研究的人和年龄<18 岁的人则被排除在外。采集巴氏涂片进行常规细胞学诊断和 P53 免疫组织化学(IHC)检测。根据改良巴氏系统对宫颈病变进行分类。
来自两个中心的 170 名参与者被招募,其中包括来自 CCSU 的 50 名 HIV 阴性对照。病例组年龄范围为 20-66 岁(平均年龄 40.5 岁),对照组年龄范围为 20-69 岁(平均年龄 41.6 岁)。36-45 岁年龄组受 HIV 影响最大(39.2%,n=47)。病例组中宫颈炎、鳞状上皮内病变(SIL)和癌分别占 28.3%(n=34)、38.3%(n=46)和 5.8%(n=7),对照组中宫颈炎、鳞状上皮内病变(SIL)和癌分别占 28%(n=14)、34%(n=17)和 2%(n=1),但差异无统计学意义(P 值=0.61)。IHC 显示 HPV+巴氏涂片和细胞块中 p53 无法检测到,表明可能发生了降解。
与 HIV 阴性对照组相比,接受高效抗逆转录病毒治疗(HAART)的 HIV 感染妇女中 SIL 和癌的发生率似乎更高,且随着年龄的增长而增加。与 HIV 阴性患者相比,HIV 阳性患者似乎更早出现 SIL,这表明 HIV 可能在改变 HPV 感染和宫颈病变的自然史方面发挥作用。HPV+病变中 p53 免疫反应缺失表明 HPV E6 蛋白能够与肿瘤抑制基因相互作用,为研究中的坦桑尼亚女性的病毒诱导致癌铺平道路。