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Abstract

Introduction Since the beginning of the HIV epidemic in Russia and St. Petersburg the population of HIV-infected women with the progression of HIV-infection and the development of opportunistic diseases, which include cervical cancer, increases. The persistence of high-risk human papillomaviruses (HR-HPV) is the major risk factor (HIV-infection is a cofactor of HPV) associated with the development of the cervical dysplasia and cancer. The impact of highly active antiretroviral therapy (HAART) on HPV infection and cervical diseases associated with HPV remains uncertain. Type-specific prevalence of HR-HPV, risk factors for cervical precancer and cancer among Russian HIV-infected women previously was not estimated. The lack of data about the features of the HPV infection and HPV-associated cervical disease, depending on the severity of the HIV-infection and using HAART in HIV-infected women of St. Petersburg, determine the aim of this study. Methods ► Prospective cohort study of the HIV-infected women receiving their care at the Center of Infectious Diseases and Prophylaxis, Saint-Petersburg, Russia between 2009 and 2013. ► Women had PCR test for HPV infection (16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59 types) from cervical canal and surface of the cervix, cervical cytology, colposcopic examinations, biopsy and histopathologic examination. ► HIV viral load and CD4 cell count were accessed as standard of care. The study enrolled 305 HIV-infected women and 90 HIV-uninfected women with HR-HPV. ► High-risk oncogenic HPV types were detected in 72,5% (n=221) of HIV-infected women. Statistically significant differences were detected with respect to 5 types HPV (31, 35, 52, 56, 59) (table 1). Table 1. The prevalence of HR-HPV among HIV/HPV co-infected women and among HIV-uninfected women with HPV HPV types HIV+/HPV+ women, n=221 HIV-/HPV+ women, n=90 n % n % 16 88 39,8 36 40,0 18 35 15,8 14 15,6 31 52 23,5* 10 11,1 33 53 24,0 16 17,8 35 23 10,4* 4 4,4 39 42 19,0 12 13,3 45 40 18,1 12 13,3 51 46 20,8 16 17,8 52 58 26,2* 12 13,3 56 69 31,2*** 8 8,9 58 28 12,7 6 6,7 59 28 12,7** 3 3,3 2 or more types 152 68,8** 44 48,9 * p<0,05 as compared with the HIV-/HPV+ group, ** p<0,01, *** p<0,001. ► Among HIV-positive women the prevalence of HR-HPV types was 77,1% (81/105) among those receiving HAART at enrollment as compared to 70% (140/200) among those not receiving HAART (p>0,05). ► The duration of HAART use 1 year or more was Also not associated with the frequency change in detection of HR-HPV (p>0,05). ► Repeated testing for HR-HPV in 12-17 (median follow-up 14,9) months after detection of an initial HPV infection performed by 81 women co-infected with HIV and HPV: in 29 cases (35,8%) HR-HPV were not identified, in 52 cases (64,2%) the virus was detected again, in 42 cases (51,9%) found again one or more same initially identified HPV types. 108 МЕДИЦИНСКИЙ АКАДЕМИЧЕСКИЙ ЖУРНАЛ, 2016 г., ТОМ 16, № 3 Results ► The frequency of re-identification of the same HPV type was different depending on the type of virus (table 2). Table 2. Results of re-identification of HR-HPV types in HIV-infected women Types of HPV HIV/HPV co-infected women, tested for the HR-HPV types again after 12-17 months, n=81 Women identified in the initial assessment of HPV types Women identified in the initial assessment of HPV types detected again not detected again n % n % 16 19 59,4 13 40,6 18 3 30,0 7 70,0 31 10 47,6 11 52,4 33 3 16,7 15 83,3 35 7 77,8 2 22,2 39 5 33,3 10 66,7 45 8 61,5 5 38,5 51 6 33,3 12 66,7 52 7 36,8 12 63,2 56 5 20,0 20 80,0 58 3 30,0 7 70,0 59 3 33,3 6 66,7 13,6% 0,9% 5,9% □ No histologically confirmed disease □ CIN I, koilocytosis □ CIN II, CIN III □ Invasive cervical cancer Figure 1. ► Abnormal results of cervical cytology were present in 21,3% (47/221) of all enrolled HIV/HPV co-infected women. Structure of cervical diseases after cervical biopsy and histological examination (was performed HIV/HPV co-infected women with abnormal results of cervical cytology and/or colposcopic examinations) is shown in figure 1. ► Among HIV/HPV co-infected women who received HAART, the proportion of patients with HPV-associated cervical pathology was 18,5% (15/81), among women without treatment of HIV infection - 21,4% (30/140) (p>0,05). ► In women receiving treatment less than one year, or without HAART, the frequency of HPV-associated cervical disease rate was higher than those, who received HAART for one year or more,- 23,8% (39/164) and 10,5% (6/57), respectively (table 3). Table 3. Structure of cervical diseases associated with HPV in HIV-infected women, depending on the duration of the usage of HAART Study group Characteristic of cervical tissue HIV-infected women with HR- HPV, receiving HAART less than 1 year or without HIV-infection treatment, n=164 HIV-infected women HAART fori with HR-HPV, receiving year or more, n=57 n % n % No histologically confirmed disease 125 76,2* 51 89,5 CIN I, koilocytosis 10 6,1 3 5,3 CIN II, CIN III, invasive cervical cancer 29 17,7* 3 5,3 * p<0,05 as compared with the group with HAART duration of one year or more. Conclusions • The prevalence of HR-HPV among HIV-infected women in St. Petersburg was 72,5%, the most prevalent genotypes were 16, 31, 33, 52, 56; Infection with multiple HR-HPV types was detected in 68,8% of case subjects with HIV/HPV co-infection. • In HIV-infected women with HPV in 64,2% cases the types of HR-HPV are detected again during the observation period of 12-17 months. • The frequency of infection by HR-HPV types in HIV-positive women does not depend on the use of HAART and the duration of treatment. Whereas the identification of CIN II, CIN III and invasive cervical cancer in HIV-infected women with HPV depends on the duration of HAART - the incidence of these diseases is 3 times lower in women receiving HAART for more than one year, in comparison with those who did not receive treatment or less of its duration. МЕДИЦИНСКИЙ АКАДЕМИЧЕСКИЙ ЖУРНАЛ, 2016 г., ТОМ 16, № 3 109 MALIGNANCIES IN HIV-INFECTED PATIENTS Nekrasova A., Popova M., Mikhaylova O., Mikhaylova N., Rassokhin V., Belyakov N. First Pavlov St. Petersburg State Medical University (Raisa Gorbacheva Memorial Research Institute of Children Oncology, Hematology and Transplantation) INTRODUCTION HIV-infected patients belong to higher risk patient group prone to malignancies development. Malignancy related mortality ranks second after random causes when antiretroviral therapy is implemented. Issues related to cancer care for HIV-infected patients become more and more topical. The objective of the current study is to define the clinical epidemiological characteristics of HIV-infected patients’ malignancies; to evaluate their overall survival rate as well as to look at the factors influencing overall survival and impeding anticancer therapy implementation. PATIENTS AND METHODS The research included 192 HIV-infected patients who were diagnosed with cancer at ‘St Petersburg Center for HIV and Infectious Diseases Control & Prevention’ during the period of 2006-2014 (Graph 1). Analysis has been performed of the initial medical records as well as of the data provided by population-based cancer registries (medical information & analytical center, MIAC). Median time of the surviving patients (n=73) was 2 years 8 months (1 month-13 years), 36% of patients were observed for more than 5 years. 70 60 50 40 30 20 10 0 RESULTS Average age of patients in the study group was 34 y.o. [17-78], men prevailed in the group - 142 people. 93% of the group had HIV diagnosed prior to cancer detection, 3,1% - received both diagnoses simultaneously. Median HIV infection duration prior to cancer diagnosis was 5 years (3 months-19 years). 95% of patients had their malignancies diagnosed at stages 4B-5 of the HIV infection development (Pokrovskiy V., 2001). Cancer antiretroviral therapy was given to 9,4% of patients, 7,8% of patients had their viral load level suppressed (abundance of mRNA less than 50 copies/ml); median level for CD4-lymphocytes amounted to 100 cell/mm3 [1-1184] and 79,2% of patients had their CD4-lymphocytes’ level below 250 cell/mm3. Cancer types breakdown, the most frequent of which was malignant lymphadenoma, is presented in graph 1 (n=111, 58%). The 4th stage of malignant tumour (TNM, Ann Arbor) was diagnosed in 80% of patients; cano (Л Graph 1. Breakdown of cancer types found in HIV-infected patients, total number of cases.