Comparative analysis of clinical treatment of HIV positive and HIV negative bladder cancer patients

doi:10.21203/rs.3.rs-2091623/v1

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Comparative analysis of clinical treatment of HIV positive and HIV negative bladder cancer patients

https://doi.org/10.21203/rs.3.rs-2091623/v1

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Objective: To provide clinical reference for the prevention and treatment of HIV positive bladder cancer by comparing and analyzing the basic information, laboratory examination, treatment and follow-up of HIV positive and non-HIV infected bladder cancer patients.

Methods: This study collected 57 bladder cancer patients with complete data who were admitted to Beijing Ditan Hospital and Beijing You 'an Hospital from 2013 to 2021, including 14 cases in the HIV positive group and 43 cases in the HIV negative group. A retrospective analysis was conducted on the HIV infection route of HIV positive patients and whether antiviral treatment was regular. The viral load and the number of CD4⁺T lymphocytes before surgery were compared. The preoperative laboratory examination, pathological grade, treatment methods, 3-month recurrence and long-term follow-up of bladder cancer patients in the two groups were compared.

Results: In this study, the average age of onset in the HIV positive group was (48.93±13.83) years old, while the average age of onset in the non-HIV group was (62.05±13.38) years old, and the difference was statistically significant (P<0.01). There were no statistically significant differences in the values of white blood cells, platelets, creatinine and albumin in preoperative laboratory tests between HIV group and non-HIV group (P>0.05), but there were statistically significant differences in red blood cell values between the two groups (P<0.05).There was no difference in pathological grade of bladder cancer between the two groups. The recurrence rate was 21.43% in HIV-positive patients and 23.26% in non-HIV patients at 3 months after surgery (P>0.05). The median long-term follow-up was 40 months (8-78 months). The survival rate of the two groups was HIV VS non-HIV (71.42% VS 93.02%) (P>0.05).

Conclusions: The clinical characteristics of HIV-positive bladder cancer patients are similar to that of the general population, and HIV positive bladder cancer patients also follow the guidelines for the general population in terms of treatment measures. The early age of HIV positive bladder cancer patients remains to be further studied.

Human immunodeficiency virus(HIV) mainly affects the immune system of the human body, including CD4⁺T lymphocytes, mononuclear macrophages and dendritic cells, etc. At present, there are about 38 million HIV-infected people in the world, and 1.7 million new people are infected every year^1,2. As high-efficiency combined anti-retrovirus therapy (HAART) is widely used, gradually extend the life of people living with HIV, the incidence of HIV merger other diseases is higher, because HIV CD4 ⁺T lymphocyte number decreasing, and even complete loss reduction in immune function of human cells, lead to all sorts of opportunistic infections and tumors, and It has been reported that HIV infection can be a risk factor for Kaposi's sarcoma and non-Hodgkin's lymphoma ^3,4. At the same time, HIV-associated urological tumors have attracted the attention of urology experts. Bladder cancer is the most common urological malignancy and the tenth most common malignancy in the world ⁵. In current studies at home and abroad, the correlation between bladder cancer and HIV infection remains unclear. It is a higher incidence of bladder cancer in low immune in the crowd, just HIV invasion of CD4⁺T cells in the immune system, infection after infection immunity low obviously, but cause or increase the risk of bladder cancer, HIV or what are the different effects on the patients after the merger of the bladder has become a key research direction in this group. In this paper, the infection route, regular antiviral therapy, preoperative viral load and number of CD4⁺T lymphocytes of HIV-positive bladder cancer patients were reported, and the relationship between HIV and bladder cancer was preliminarily discussed. The clinical characteristics, treatment measures and pathology of HIV-positive bladder cancer patients and non-HIV bladder cancer patients were compared. And the difference and connection between guiding principles. To provide reference for clinical treatment of HIV positive bladder cancer patients.

This study collected the information of bladder cancer patients treated in Beijing Ditan Hospital and Beijing You 'an Hospital from 2013 to 2021. Basic information, HIV infection status, HIV infecence-related data and bladder cancer related data were collected by consulting the patient's medical records. Basic patient information includes gender and age. HIV infection-related data included the patient's infection route, HAART status, preoperative CD4⁺T lymphocyte count, and preoperative viral load. Data related to bladder cancer included preoperative laboratory examination, surgical method, pathological type, pathological grade, 3 months postoperatively review results, and long-term follow-up results. Patients with common bladder cancer with incomplete clinical data were excluded from the study. The study divided patients into two groups: HIV-positive and non-HIV. Quartile spacing,t test, χ2 test and Fisher's exact probability were used to analyze the data.

Basic information

This study included 57 bladder cancer patients treated in Beijing Ditan hospital and Beijing You 'an hospital from 2013 to 2021, including 14 HIV-infected patients and 43 Non-HIV-infected patients (Table1). The mean age of onset in HIV-positive bladder cancer patients was (48.93±13.83) years old, while that in non-HIV patients was (62.05±13.38) years old, and the difference was statistically significant (P<0.01, t-test,Figure1). The majority of non-HIV patients were male (38 cases,88.37%) and the majority of HIV positive patients were male (13 cases,92.86%). Among the 14 HIV positive bladder cancer patients, 6 cases were infected with homosexual sex, 3 cases were infected with heterosexual sex, and 5 cases were infected with unknown cause. There were 7 patients receiving regular antiretroviral therapy, and there were 12 patients with preoperative CD4⁺T lymphocyte count ≧200cells/ul. Except for 4 patients whose viral load was not detected, the viral load of the other 10 patients was below 100copies/ml or even not detected.

Table1 Basic information and HIV related data

Abbreviations: NT not tested, TND target not detected

Preoperative laboratory tests

By comparing the preoperative laboratory test results of HIV positive and non-HIV bladder cancer patients (Table2, Figure2), there was no statistical significance in the white blood cells, platelets, creatinine and albumin values between HIV group and non-hiv group (P>0.05). However, the red blood cell difference between the two groups was statistically significant (P=0.043<0.05).

Table2 Analysis of HIV and non-HIV laboratory tests

Variables	HIV	Non-HIV	P value
WBC（10^9/L）*	6.165（4.935，7.02）	6.24（4.93，7.13）	0.831
RBC（10^12/L）*	4.16（3.695，4.6775）	4.68（4.08，4.95）	0.043
Platelets（10^9/L）#	199±60.05	207.6±63.82	0.659
Creatinine（μmol/L）*	70.85（65.5，75.25）	69.5（67，85.6）	0.541
Albumin（g/L）*	41.5（39.6，44.45）	44.7（41.1，46.3）	0.159

Abbreviations：#.Mean±SD;*.M（Q1,Q3)

Pathology, treatment, and outcomes

According to the pathological analysis of HIV positive and non-HIV bladder cancer patients, the pathological type of 14 HIV positive bladder cancer patients and 43 non-HIV bladder cancer patients was uroepithelial carcinoma（Table3）. Muscle invasive bladder cancer(MIBC) patients accounted for 21.43% in HIV positive patients and 25.58% in non-HIV patients, with no statistical significance (P>0.05). High-grade urothelial carcinoma was 35.72% in HIV positive group and 55.82% in non-HIV group, with no statistical significance (P>0.05). The surgical method was selected according to the tumor size, invasion depth and patients' wishes. 78.57% of the HIV-positive patients chose transurethral resection of bladder tumors(TURBT) for treatment, while 93.02% of the non-HIV patients chose TURBT. It is worth mentioning that all patients chose pirubicin for bladder infusion after TURBT treatment. All patients who chose radical surgical treatment received gemcitabine + cisplatin 2-3 cycles of chemotherapy. The patients were reexamined 3 months after surgery. Cystoscopy and Urinary CT were performed in patients with TURBT surgery, and urinary CT was performed in patients with radical surgery. The recurrence rate of HIV positive patients was 21.43% 3 months after surgery, while that of non-HIV patients was 23.26% 3 months after surgery. There was no statistical significance in the recurrence rate between the two groups 3 months after surgery (P>0.05). In addition, 4 HIV positive patients did not undergo reexamination 3 months after surgery. Recently, the two groups of patients were followed up by telephone, and the survival of the two groups was HIV VS non-HIV (71.42% VS 93.02%), with no statistical significance (P>0.05). In the HIV group, 2 patients were lost to follow-up, which was not calculated as survival patients.

Table3 Pathology, treatment, and outcomes in HIV-positive and non-HIV patients with bladder cancer

HIV has been widely studied worldwide. In addition to kaposi's sarcoma, which is known to be an HIV-associated tumor, HIV also increases the risk of other cancers, such as skin squamous cell carcinoma, anal carcinoma, etc. ^6,7 .However, HIV positive bladder cancer patients are relatively rare in the world. So far, there are only a few case reports or serial case descriptions, and no study has compared HIV positive and non-HIV bladder cancer. This is the first study to compare HIV positive and non-HIV bladder cancer in terms of basic information, laboratory tests, pathological types, treatment and follow-up.

In this study, the average age of onset in the HIV group was (48.93±13.83) years, while that in the non-HIV group was (62.05±13.38) years. The age of onset was significantly older in the non-HIV group than in the HIV group. Previous studies have shown that the median age of HIV/AIDS onset is 40 years old, which also indirectly indicates that the age of HIV patients in this study is significantly younger than that of non-HIV patients, which may be related to HIV infection ⁸. HIV is a virus that attacks the human immune system. It mainly destroys CD4⁺ T lymphocytes, leading to immune deficiency in the human body, which increases the risk of tumor occurrence ⁹. Studies show that: The risk of cancer among people living with HIV is 1.6-1.7 times that of the general population ^10,11. In addition, HIV infected people are more likely to be frequently infected with other carcinogenic factors, such as EB virus, human herpes virus 8 [HHV-8], human papilloma virus [HPV], hepatitis b and hepatitis c virus [HBV, HCV], etc. Further increase the risk of tumor occurrence ^12,13. Fortunately, there were only two cases of syphilis infection in the HIV group in this study, and no other tumor-related virus infection. In addition, the majority of HIV-infected patients have been regularly referred for antiretroviral therapy since the discovery of HIV, which allows them to detect other diseases, such as bladder cancer, earlier in the check-up process. In this study, the two groups of patients were mainly male, among which 92.86% were male in the HIV group and 88.37% were male in the non-HIV group, because bladder cancer itself was more common in men, which was consistent with Siegel LS et al. ¹⁴. The proportion of male patients in the HIV group was slightly higher, but the difference was not statistically significant. This difference may be due to the low number of HIV patients, but HIV itself is more common in men, which may explain the higher proportion of men in the HIV group.

In this study, we still found that the values of white blood cells, red blood cells, platelets, creatinine and albumin in two groups were basically within the normal range. Except for red blood cells, there was no significant difference in other laboratory tests, but the red blood cell values in the HIV group were significantly lower than those in the non-HIV group. Through the literature, we found that the HIV infection can result in myelodysplastic syndrome, polycythemia vera disease, etc., which can lead to anemia, low white blood cells of patients with 6, 15, so the HIV positive patients than HIV negative groups were examined by red blood cells is low, as for HIV positive patients the hematology indexes basic within the normal range, This may be related to the significantly improved immune function of HIV-positive patients after regular antiviral therapy, which is close to the normal level. At least, in this study, the patients' viral load and CD4+T lymphocytes were well controlled. It should be noted that despite regular HAART treatment in HIV-positive patients, hematologic indexes tend to be lower than those in non-HIV patients. If HIV-positive patients do not receive regular HARRT treatment, their related indexes may be worse, immune function may be lower, and the risk of bladder cancer may be further increased. Of course, the reason why the hematological indexes of HIV patients are lower than those of the normal group still needs further research.

Urinary tract carcinoma is the main pathological type of bladder cancer¹⁶.in this study, the pathology of both groups was urinary tract carcinoma without any other pathological type, which was related to the small sample size of this study. Nonmuscle invasive bladder cancer(NMIBC) accounts for 78.57% in the HIV group and 74.42% in the non-HIV group, which is consistent with previous reports that NMIBC accounts for over 70% of bladder cancer^17,18. Patients in both groups were followed up 3 months after surgery and in the long term by telephone, and the median long term follow-up time was 40 months. The recurrence rate was 21.43% in the HIV group and 23.26% in the non-HIV group 3months after surgery, among which all the recurrent cases were NMIBC. During the long-term follow-up, we found that there was no significant difference in the death of two groups, which was largely related to the regular antiviral treatment in the HIV group. Studies have shown that with the advent and improvement of antiretroviral therapy, the mortality rate of HIV-infected patients has decreased significantly, as has the mortality rate of HIV-related cancers, and at least no increased risk of morbidity and mortality has been observed for any cancer ^19,20. Although the follow-up time of this study is short and the number of patients is limited, the patient outcome indicators also indicate that under the condition of good HIV control, surgery for HIV-positive bladder cancer patients is safe and effective, and the survival rate will be greatly improved.

In this study, the clinical manifestations, treatment measures, pathological types and survival rates of HIV-infected bladder cancer patients were similar to those of non-HIV bladder cancer patients under the condition that HIV was well controlled. Treatment of HIV-positive patients with bladder cancer also follows clinical guidelines for bladder cancer. For HIV positive bladder cancer, the younger age of onset and lower laboratory examination than non-HIV need to be further studied.

Acknowledgements

We would like to thank our collaborators in the pathology department for their great efforts to the study.

Authors’ contributions

Yu Zhang and Xiaolin Su and Xuyu Li contributed research design, data collection, manuscript writing/editing. Wenrui Xu and Xudong Wang and Pengfei Yuan contributed statistic analysis.Xin Wang and Qingjun Liu contributed table1.Zhixing Han contributed table2.Haijian Zhang contributed Figure1.Rurun Liang and Yi Cui contributed Figure2.Shiqi Ji revised the manuscript. The authors read and approved the final manuscript.Corresponding authors are Qingjun Liu and Shiqi Ji.Corresponding author Email:[email protected]

Funding

Beijing Medical Award Fund(YXJL-2021-0800-0410).Availability of data and materials.All data generated or analyzed during this study are included in this published article.

Ethics approval and consent to participate the research was reviewed and approved by the Ethics Committee of Beijing Ditan Hospital Capital Medical University. All the participants provided informed consent.

Consent for publication

Written informed consent for publication was obtained from all participants.

Competing interests

The authors declare that they have no competing interests

Author details 1Department of Urology, Beijing Ditan Hospital, Capital Medical University,

Beijing, China. 2Department of Emergency,Beijing First Integrated Traditional Chinese and Western Medicine Hospital. 3Department of Urology, Beijing Youan Hospital, Capital Medical University, Beijing, China.

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Comparative analysis of clinical treatment of HIV positive and HIV negative bladder cancer patients

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