High incidence of anal cancer among AIDS patients

doi:10.1016/S0140-6736(94)92636-0

The Lancet

Volume 343, Issue 8898, 12 March 1994, Pages 636-639

https://doi.org/10.1016/S0140-6736(94)92636-0 Get rights and content

Abstract

Until now, the only cancers that have been strongly associated with AIDS are Kaposi's sarcoma and non-Hodgkin lymphoma. We used a linkage between AIDS (50 050 reports) and cancer (859 398 reports) registries in seven health departments in the USA to investigate the association between HIV infection and epidermoid anal cancer. We compared the numbers of observed cases and expected cases, calculated from general population rates with adjustment for age, sex, and race. The relative risk of anal cancer at and after AIDS diagnosis was 84·1 (95% Cl 46·4-152) among homosexual patients (11 cases) and 37·7 (9·4-151) among non-homosexual patients (2 cases). The relative risk of anal cancer up to 5 years before the AIDS diagnosis (23 cases) was also increased; it was 13·9 (6·6-29·2) in the period 2-5 years before AIDS and 27·4 (15·9-47·2) during the 2 years before AIDS diagnosis (p for trend=0·004). Among homosexual men, the relative risk of anal cancer was inversely related to age at AIDS onset (p for trend<0·001). Excess risks were found in all geographical areas. This study establishes a strikingly increased risk of anal cancer among people with AIDS. These data are consistent with a previously hypothesised association between HIV-induced immunodeficiency and anal cancer development, but because homosexual men were at increased risk of anal cancer even before the AIDS epidemic, we cannot say how much of the increased risk is attributable to HIV infection. Nevertheless, clinicians should be aware that AIDS patients have an increased risk of anal cancer.

References (31)

Jh Scholefield et al.
Anal and cervical intraepithelial neoplasia: possible parallel
Lancet
(1989)
M. Melbye et al.
Aetiological parallel between anal cancer and cervical cancer
Lancet
(1991)
Jh Scholefield et al.
Anal epithelial neoplasia: part of a multifocal disease process
Lancet
(1992)
Ih Frazer et al.
Association between anorectal dysplasia, human papillomavirus, and human immunodeficiency virus infection in homosexual men
Lancet
(1986)
S. Goldman et al.
Incidence of anal epidermoid carcinoma in Sweden 1970-1984
Acta Chir Scand
(1989)
M. Frisch et al.
Trends in incidence of anal cancer in Denmark
BMJ
(1993)
M. Melbye, Cs Rabkin, M. Frisch, Rj Biggar, Changing patterns of anal cancer incidence in the USA, period 1940-89, Am J...
Cdc
1993 revised classification system for HIV infection and expanded surveillance case definition for AIDS among adolescents and adults
MMWR
(1992)
Cs Rabkin et al.
Second primary cancers following anal and cervical carcinoma: evidence of shared etiologic factors
Am J Epidemiol
(1992)
M. Melbye et al.
Immune status as a determinant of human papillomavirus detection and its association with anal epithelial abnormalities
Int J Cancer
(1990)

D. Caussy et al.

Interaction of human immunodeficiency virus and papillomaviruses: association with anal epithelial abnormality in homosexual men

Int J Cancer

(1990)

Jm Palefsky et al.

Anal intraepithelial neoplasia and anal papillomavirus infection among homosexual males with group IV disease

JAMA

(1990)

Jm Palefsky et al.

Natural history of anal cytologic abnormalities and papillomavirus infection among homosexual men with group IV disease

J Acq Immun Defic Syndr

(1992)

Rj Biggar et al.

Risk of other cancers following Kaposi's sarcoma: relationship to the acquired immunodeficiency syndrome

Am J Epidemiol

(1994)

Tr Coté

NCI plans linkage of AIDS and cancer registries

J Natl Cancer Inst

(1993)

Cited by (261)

Incidence and mortality of non-AIDS-defining cancers among people living with HIV: A systematic review and meta-analysis
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Citation Excerpt :
We identified 92 publications arising from 46 independent studies (Figure 1). Forty-two studies (85 publications12–53,64,69–79,81–111) only reported the outcome of cancer-specific SIRs among PLHIV, four studies (6 publications54–58,112) only reported the outcome of SMRs, and one study reported both the outcome of SIRs and SMRs. Details of included publications are in the supplementary Table S1.
Non-AIDS-defining cancers (NADCs) are now becoming a rising cause of morbidity among people living with HIV (PLHIV) in the highly active antiretroviral therapy (HAART) era. We conducted a systematic review and meta-analysis to estimate the summary risk of incidence and mortality of a wide range of NADCs among PLHIV compared with the general population.
This systematic review and meta-analysis was registered in the PROSPERO (registration number CRD42020222020). We searched PubMed, EMBASE, Cochrane library, and Web of Science for relevant studies published before Jan 24, 2022. Cohort or registry linkage studies comparing the incidence or mortality of individual NADCs in PLHIV with that in the general population were included. Studies simply reporting outcomes of cancer precursor lesions or combined NADCs were excluded. We calculated pooled standardised incidence (SIRs) and standardised mortality ratios (SMRs) and their 95% confidence intervals (CIs) using random-effects models, and used robust variance estimation to account for non-independence in study-level effect sizes.
We identified 92 publications arising from 46 independent studies including 7 articles out of 7 studies from developing countries. Among the 40 types of NADCs investigated, all of the 20 infection-related NADCs, cancers related with human papillomavirus infection in particular, and half of the 20 non-infection-related NADCs occurred in excess in PLHIV compared with the general population. This risk pattern was consistent in most WHO regions and in both high-income and low-and middle-income countries. The increased SIRs for various NADCs were more evident among PLHIV with advanced immunodeficiency, and was explored by HIV transmission route, and use of HAART. PLHIV had increased mortality for anal cancer (SMR 124·07, 95% CI 27·31-563·72), Hodgkin lymphoma (41·03, 2·91−577·88), liver cancer (8·36, 3·86−18·11), lung cancer (3·95, 1·52-10·26), and skin melanoma (3·95, 1·28−12·2).
PLHIV had increased incidence and mortality for a wide spectrum of NADCs. Primary prevention and effective treatment for NADCs in this population is urgently needed.
Natural Science Foundation of China Excellent Young Scientists Fund, Natural Science Foundation of China International/Regional Research Collaboration Project, National Science and Technology Major Project of China, Sanming Project of Medicine in Shenzhen, High Level Project of Medicine in Longhua, Shenzhen, Shenzhen Science and Technology Innovation Commission Basic Research Program, Special Support Plan for High-Level Talents of Guangdong Province, the Guangzhou Basic Research Program on People's Livelihood Science and Technology, the National Natural Science Foundation of China.
Neuroendocrine-immune Interface: Interactions of Two Complex Systems in Health and Disease
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The relationship between the neuroendocrine and the immune systems is essential to maintain homeostasis. Their complex interactions are present in many physiological or pathological states whereby hormones exert different actions in immune system cells and vice versa. Hormones such as prolactin, growth hormone, cortisol and sex hormones are known to regulate the differentiation and function of immune system cells and the production of cytokines. Many of these cells express hormone receptors leading to the tempering of several autoimmune and neoplastic diseases. The pituitary gland is susceptible to autoimmune damage, be it because of primary lymphocytic hypophysitis, as part of IgG4-related disease or as an adverse event of treatment with immune checkpoint inhibitors (ICi). Finally, pituitary adenomas, like many other neoplasms, are frequently infiltrated by different cells of the immune system, a phenomenon that can be related to the degree of invasiveness of these lesions. The purpose of the present work is to critically analyze the neuroendocrine-immune interphase, from both a biological and a clinical perspective.
Anal Carcinoma
2015, Clinical Radiation Oncology
Does high-risk human papilloma virus genotyping of abnormal anal cytology improve detection of high-grade anal intraepithelial neoplasia?
2014, Journal of the American Society of Cytopathology
High-risk (HR) human papillomavirus (HPV) testing is accepted as the standard of care for surveillance of cervical cancer. Its role in anal cancer is not clear. This study was therefore designed to determine if HR HPV genotyping is a useful adjunct in management of abnormal anal Papanicolaou (Pap) tests.
HR HPV genotyping and virus quantification was performed on 101 residual anal Pap test samples (28 negative, 25 atypical squamous cells of undetermined significance [ASC], 34 low-grade squamous intraepithelial lesion [LSIL], 6 atypical squamous cells of undetermined significance, cannot exclude high-grade squamous intraepithelial lesion, and 8 high-grade squamous intraepithelial lesion) using multiplex real-time polymerase chain reaction. Results were correlated with cytodiagnosis and follow-up.
HR HPV was detected in 82% (50% negative, 84% ASC, and 100% LSIL and above) cases. Multiple genotypes were present in 71% of cases. Genotype number and viral load correlated with the degree of anal cytologic abnormality. HPV 16, 18, and 45 were the most frequent genotypes detected. The high frequency of HR HPV in abnormal anal cytologies limits its use as an adjunct test. Anal Pap test samples with anal intraepithelial neoplasia 2/3 (AIN 2/3) on follow-up were positive for HPV 16 and/or 18 (HPV 16/18+) in 80% of cases. We hypothesize that testing for HPV 16/18 on the ASC and LSIL cases would have detected AIN 2/3 with a sensitivity of 81%, specificity of 43%, positive predictive value of 39%, and negative predictive value of 83%.
Our results with a small cohort suggest that genotyping for HPV 16/18 may be effective in identifying patients at high risk for anal cancer and in reducing the number of anoscopy referrals. Prospective studies with follow-up are warranted.
Anal carcinoma and HIV infection: Is it time for screening?
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Varón de 38 años, diagnosticado de infección por el virus de la inmunodeficiencia humana (VIH) hace 10 años, y que seguía desde entonces terapia antirretroviral. Nunca había presentado enfermedades oportunistas y se encontraba en buena situación inmunológica, con recuento de CD4 de 450 células/mm³ y carga viral de VIH indetectable. Consultaba por presentar molestias anales persistentes desde hacía 2 meses, con prurito y leve sangrado ocasional. Al haber presentado varios episodios previos de verrugas anales, el paciente se había autoadministrado diversos tratamientos tópicos, sin eficacia y con empeoramiento de los síntomas. La exploración de la región perianal evidenció eritema inespecífico y signos de rascado. En el tacto rectal se detectaba una pequeña tumoración de 0,5 cm y base infiltrada, dolorosa a la palpación y localizada a 15 mm del orificio anal. Se realizó una anoscopia de alta resolución con biopsia de la lesión descrita, que confirmó la presencia de un carcinoma epidermoide infiltrante.
¿Habría podido prevenirse el desarrollo de esta neoplasia?
A 38-year-old white man had a 10-year history of human immunodeficiency virus (HIV) infection (A3), with no episodes of opportunistic diseases and in good immunologic recovery (CD4 cell count: 450 and indetectable HIV viral load) while on HAART. He presented with a two-month history of mild anal symptoms, including pruritus and episodic bleeding. He referred past episodes of anal warts, self-treated with several topical compounds, all proven unsuccessful. Perianal examination showed erythema and scratching. A 0.5 cm sized tumor, with infiltration at the base was detected on digital exam, located at 15 mm from the anal margin. Local biopsy driven by high-resolution anuscopy (AAR) yielded a final diagnosis of infiltrative epidermoid carcinoma.
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¹: Members of the working group are listed at the end of the article.

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High incidence of anal cancer among AIDS patients

Abstract

Lancet

Lancet

Lancet

Lancet

Incidence of anal epidermoid carcinoma in Sweden 1970-1984

Acta Chir Scand

Trends in incidence of anal cancer in Denmark

BMJ

1993 revised classification system for HIV infection and expanded surveillance case definition for AIDS among adolescents and adults

MMWR

Second primary cancers following anal and cervical carcinoma: evidence of shared etiologic factors

Am J Epidemiol

Immune status as a determinant of human papillomavirus detection and its association with anal epithelial abnormalities

Int J Cancer

Interaction of human immunodeficiency virus and papillomaviruses: association with anal epithelial abnormality in homosexual men

Int J Cancer

Anal intraepithelial neoplasia and anal papillomavirus infection among homosexual males with group IV disease

JAMA

Natural history of anal cytologic abnormalities and papillomavirus infection among homosexual men with group IV disease

J Acq Immun Defic Syndr

Risk of other cancers following Kaposi's sarcoma: relationship to the acquired immunodeficiency syndrome

Am J Epidemiol

NCI plans linkage of AIDS and cancer registries

J Natl Cancer Inst