REGULAR ARTICLECD4 Lymphocytes in Women with Invasive and Preinvasive Cervical Neoplasia
Abstract
Objective.To assess the relationship between CD4 lymphocyte population and stage of disease in cervical neoplasia.Methods.Study population was 107 women with invasive cervical cancer, 116 women with cervical intraepithelial neoplasia (CIN), and 32 women without neoplasia diagnosed in 1988–1994. All women under age 50 were seronegative for the human immunodeficiency virus (HIV). All women over age 50 with CD4:CD8 ratio below normal were HIV-negative. Stage was defined by FIGO criteria using clinical findings. CD4 and CD8 lymphocyte populations were enumerated by flow cytometry prior to treatment. The normal range of CD4 counts was defined as 537–1571 cells/mm3.Results.Distribution of CD4 count was similar in stages I (n= 40), II (n= 24), and III (n= 32), with 31% below normal and 9% above normal (mean CD4 count = 881). However, in stage IV (n= 11), 64% were below normal and 18% above normal (mean CD4 = 591). The difference in distribution between stages I–III and stage IV was statistically significant. Among 116 CIN patients, 10% had CD4 counts below normal and 3% above normal (mean CD4 = 910). Among 32 women without cervical neoplasia, 0% had CD4 counts below normal and 3% above normal. The difference between CIN and invasive cancer in the distribution of CD4 counts and CD8 counts was significant (P< 0.01). There was no difference in the CD4 count distribution by CIN severity. Forty-five percent of patients with below-normal CD4 counts at diagnosis developed recurrent cancer compared to 43% of patients with normal or above-normal CD4 counts.Conclusion.Women with invasive cervical cancer have lower CD4 counts and a broader distribution compared to women with preinvasive or no neoplasia. Metastatic cancer at diagnosis was associated with severely depressed CD4 count.
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HIV impact on acute morbidity and pelvic tumor control following radiotherapy for cervical cancer
2006, Gynecologic OncologyTo determine the impact of HIV infection on acute morbidity and pelvic tumor control following external beam radiotherapy (EBRT) for cervical cancer.
218 patients receiving EBRT who also had HIV testing after informed consent was obtained were evaluated. Acute treatment toxicity was documented weekly during treatment and 1 month post-EBRT. Pelvic tumor control was documented at 4 and 7 months post-EBRT. Clinicians were blinded for HIV results.
About 20% of the patients were HIV-positive. Overall, 53.4% of the patients had radiation-related acute toxicity (grade 3–4). HIV infection was associated with a 7-fold higher risk of multisystem toxicity: skin, gastrointestinal tract (GIT) and genitourinary tract (GUT) systems. It was also an independent risk factor for treatment interruptions (adjusted relative risk 2.2). About 19% of the patients had residual tumor at 4 and 7 months post-EBRT. HIV infection was independently and significantly associated with 6-fold higher risk of residual tumor post-EBRT. The hazard ratio of having residual tumor after initial EBRT was 3.1-times larger for HIV-positive than for HIV-negative patients (P = 0.014).
HIV is associated with increased risk of multisystem radiation-related toxicity; treatment interruptions and pelvic failure (residual tumor) following EBRT. HIV infection is an adverse prognostic factor for outcome of cervical cancer treatment.
The cell-mediated immune response to human papillomavirus-induced cervical cancer: Implications for immunotherapy
2002, Advances in Cancer ResearchThe chapter presents the evidence that human papillomaviruses (HPV) are linked with the development of several human malignancies, including carcinomas of the upper aerodigestive tract and the anogenital tract, as well as conjunctival carcinomas from molecular, clinical, and epidemiological studies. This chapter focuses on the role of cellular immunity and prospects for immunotherapy in HPV-related cervical malignancies. Cervical cancer remains the third most common cancer among women worldwide, with approximately 400,000 new cases per year. HPV DNA has been demonstrated in more than 99.7% of tumor biopsy specimens, with high risk HPV16 and HPV18 sequences being the most prevalent. Cell-mediated immunity is likely to play an important role in protecting against tumor progression, as shown by the increased frequency of HPV-associated tumors in individuals treated with immunosuppressive drugs or suffering from AIDS. In addition, malignant lesions are characterized by an infiltration of CD8+ T cells. The chapter emphasizes that an effective vaccine that would mount a cellular immune response against HPV-related proteins might contribute to the elimination or prevention of HPV-expressing lesions, including cervical carcinomas. The goal of therapeutic immunization against HPV-induced carcinomas is to induce cellular components of the immune system to recognize and attack cells infected with HPV, including malignant tissue. Modulation of the immune response to HPV-infected cells is possible through many different vaccination strategies. Therefore, clinical trials have not been very successful in achieving significant tumor regression, most likely because the diseases were too advanced to treat with immunological intervention.
HIV and cervical cancer in Kenya
2002, International Journal of Gynecology and ObstetricsObjectives: To determine the effect of the HIV epidemic on invasive cervical cancer in Kenya. Methods: Of the 3902 women who were diagnosed with reproductive tract malignancies at Kenyatta National Hospital (KNH) from 1989 to 1998, 85% had invasive cervical cancer. Age at presentation and severity of cervical cancer were studied for a 9-year period when national HIV prevalence went from 5% to 5–10%, to 10–15%. Results: There was no significant change in either age at presentation or severity of cervical cancer. Of the 118 (5%) women who were tested for HIV, 36 (31%) were seropositive. These women were 5 years younger at presentation than HIV-negative women. Conclusions: A two- to three-fold increase in HIV prevalence in Kenya did not seem to have a proportional effect on the incidence of cervical cancer. Yet, HIV-positive women who presented with cervical cancer were significantly younger than HIV-negative women.
An overview of sexually transmitted diseases. Part III. Sexually transmitted diseases in HIV-infected patients
2000, Journal of the American Academy of DermatologyThe HIV epidemic has dramatically altered the field of sexually transmitted diseases (STDs). HIV infection is unique among sexually transmitted diseases because it can modify the clinical presentation and features of other STDs. Conversely, other STDs can affect the transmission of HIV. This review is the third part of a series that has provided a general overview of STDs. In this article, genital ulcer diseases (genital herpes, syphilis, chancroid, lymphogranuloma venereum, and granuloma inguinale), human papillomavirus infection (anogenital warts and subclinical infections), molluscum contagiosum, human herpesvirus 8 infection, viral hepatitis, and ectoparasitic infestations (scabies and pediculosis pubis) are discussed as they occur in HIV-infected hosts. Additional features as they relate to HIV-infected patients, such as epidemiology and transmission, are discussed when applicable. Learning objective: At the conclusion of this learning activity, participants should improve their understanding of sexually transmitted diseases in the HIV-infected host. (J Am Acad Dermatol 2000;43:409–32.)
Cutaneous and genital HPV-Associated lesions in HIV-infected patients
1997, Clinics in Dermatology