Download PPS format (self-contained PowerPoint show)

Special Symposium of
the Essex County Cancer Coalition
September 22, 2011
Can Sex Lead to Cancer?
• HIV/AIDS and Cancer
• Drugs and Cancer
Presented by:
Stanley H. Weiss, M.D.
Professor of Preventive Medicine and Community Health,
UMDNJ-New Jersey Medical School
Professor of Quantitative Methods, School of Public Health
Director, Essex County Cancer Coalition
30 Bergen Street
Bldg. ADMC 16, Room 1614
Tel: (973) 972-4623
[email protected]
www.umdnj.edu/esscaweb
© 2011, SH Weiss. All rights reserved.
Sexually transmitted infection and
diseases (STI’s & STD’s)
What is special
about STI’s and
STD’s as compared
to other infectious
agents/diseases?
(c) Stanley H. Weiss MD. Newark NJ
3
Sexually transmitted infection and
diseases (STI’s & STD’s)
“Sex” and Sexual Practices
o Reluctance to discuss with partner
 History may be unknown, even if
discussed, or misrepresented
o Intimate behavior:
 Lesions may not be seen
• Lighting
• Sexual practices
o Infected person may not even know
o Reluctance to discuss with
healthcare provider, and vice-versa
(c) Stanley H. Weiss MD. Newark NJ
4
Sexually transmitted infection and
diseases (STI’s & STD’s)
• Lack of immune protection
 Persistence of certain agents
 Continual susceptibility to others
 Lack of vaccines
• Limitations of barrier methods
(c) Stanley H. Weiss MD. Newark NJ
5
HIV/AIDS
H
Human
I
Immunodeficiency
V
Virus
A
Acquired
I
Immuno
D
Deficiency
S
Syndrome
HIV
AIDS
• Once a person is infected they are always
infected
• Medications are available to prolong life but
they do not cure the disease
• Those who are infected are capable of
infecting others without having symptoms or
knowing of the infection
HIV and Cancer Risk
People infected with HIV have a
substantially higher risk of some
types of cancer compared with
uninfected people of the same age.
They also often have a multiplicity of
other cancer risk factors.
HIV’s Effect on Cancer Risks
Three cancers are known as “acquired
immunodeficiency syndrome AIDS-defining
cancers” or “AIDS-defining malignancies”; a
diagnosis of any of these marks that HIV
infection has progressed to AIDS.
Cancer
Increased Risk*
Kaposi’s sarcoma (KS)
Primary CNS lymphoma
Non-Hodgkin’s lymphoma (NHL)
Invasive cervical cancer
> 1,000
≈ 1,000
23-70
5
* Standardized incidence ratio (SIR)
HIV’s Effect on Cancer Risks
In addition, people infected with HIV are at
higher risk of several other types of cancer,
including:
Cancer
Anal
Hodgkin’s lymphoma (HL)
Liver
Penis
Lung
Larynx
Mouth or pharynx
Increased Risk (SIR)
20-25
10-14
5
8
3
3
2
HIV’s Effect on Cancer Risks
No evidence of increased risk of
these other common cancers:
• Breast
• Prostate
• Colorectal
Among the non-AIDS defining tumors, the most
common overall in HIV-infected patients is lung cancer
because it has a high underlying incidence in the
general population.
HIV’s Effect on Cancer Risks
Infection with HIV weakens the immune system
and reduces the body's ability to fight infections
that may lead to cancer.
Many infected with HIV are also infected with
other viruses that cause certain cancers. The most
important of these cancer-related viruses: …
…
HIV’s Effect on Cancer Risks
• Human herpesvirus 8 (HHV-8), also known as Kaposi sarcomaassociated herpesvirus (KSHV), is the cause of Kaposi sarcoma.
• Epstein Barr virus (EBV) causes some subtypes of non-Hodgkin
and Hodgkin lymphoma.
• Human papillomavirus (HPV) causes cervical cancer and some
types of anal, penile, vaginal, vulvar, oropharyngeal and head
and neck cancer.
• Hepatitis B virus (HBV) and hepatitis C virus (HCV) both can
cause liver cancer.
• Human T-cell lymphotropic Virus Type I (HTLV-I), which causes
adult T-cell lymphoma; this virus and this disease are rare in the
U.S.
Infection with most of these viruses is more common among
people infected with HIV than among HIV-uninfected people.
HIV’s Effect on Cancer Risks
Some traditional risk factors for cancer,
especially smoking (a known cause of lung
cancer) and heavy alcohol use (which can
increase the risk of liver cancer), are higher
among people infected with HIV.
HIV’s Effect on Cancer Risks
The introduction of highly active antiretroviral
therapy (HAART) in the mid-1990s greatly
reduced the incidence of Kaposi sarcoma and
non-Hodgkin lymphoma among people infected
with HIV. HAART lowers the amount of HIV
circulating in the blood, thereby allowing partial
restoration of immune system function.
HIV’s Effect on Cancer Risks
The incidence of several other cancers, particularly
Hodgkin’s lymphoma and anal cancer, has been
increasing among HIV-infected individuals since the
introduction of HAART. The influence of HAART on
the risk of these other cancer types is not well
understood.
The higher incidence of liver cancer among HIVinfected people appears to be related to more
frequent infection with hepatitis virus (particularly
HCV) and alcohol abuse or dependence than
among uninfected people.
Routes of Transmission of HIV
Sexual Contact:
Male-to-male
Male-to-female
Female-to-male
Female-to-female
Blood Exposure:
Injecting drug use/needle sharing
Occupational exposure
Transfusion of (unscreened) blood products
Perinatal:
Transmission from mother to neonate
Breastfeeding
HIV Transmission
• HIV Parenteral Transmission
HIV enters the bloodstream through:
–
–
–
–
–
Direct injection
Open cuts
Breaks in the skin
Breaks in mucous membranes
Examples:
• IDU/contaminated paraphernalia
• sharps & needlestick exposures
• prior to screening: blood products (risk is now rare in developed
countries due to screening)
Comparative transmission risks for HIV, HBV and HCV,
from a needlestick with blood contaminated with that agent
Agent
Percutaneous Exposure
Transmission Risk (Range)
HIV
0.3% (95% CI 0.2–0.5%)
HCV
1.8% (range 0–7%)
HBV, HBsAg + ,
HBeAg negative
Serologic: 23–37%
Clinical hepatitis: 1–6%
HBV, HBsAg + ,
HBeAg positive
Serologic: 37–62%
Clinical hepatitis: 22–31%
HIV Transmission
• HIV Sexual Transmission
– From a person infected with HIV to an uninfected
person (discordant pair)
• Anal
• Genital
• Oral (rare)
HIV Transmission
• Body fluids that are a frequent source of
transmission:
– Blood
– Semen
– Vaginal Secretions
– Breast Milk
HIV in Body Fluids
Blood
18,000
Semen
11,000
Vaginal
Fluid
7,000
Amniotic
Fluid
4,000
Saliva
1
Average number of HIV particles in 1 ml of these body fluids
HIV Transmission Risk
Varies with the Sexual Act (1)
When the Partners are HIV Discordant:
Highest Receptive partner, anal intercourse
Insertive partner, anal intercourse
Penile-vaginal: greater risk to women
than to men
Lowest Orogenital
HIV Transmission Risk
Varies with the Sexual Act (2)
• Known modulating factors:
– STI co-infection: ↑ in transmission rate
– STI infection: ↑ receptivity rate
– Degree of HIV viremia
– HAART: ↓ viral titer → ↓ transmission
– Barrier methods
HIV Transmission Risk
Varies with the Sexual Act (3)
• Possible modulating factors
– Rough sex
• Increased mucosal injury
• Condom breakage
– Blood exposure
– ? Intercourse during menses ?
Understanding changing epidemiologic patterns:
unifying concepts and examples [9]
HOMOSEXUALITY & BISEXUALITY
•
“Do you have sex only with men, only with
women, or with both?”
•
Specific sexual practices with sameand/or opposite-sex partners
•
Specific sexual practices may be associated
with specific problems
“When you have sex with
someone, you are having sex with
everyone they have had sex with
for the last ten years.”
Former Surgeon General
C. Everett Koop
Understanding changing epidemiologic patterns:
unifying concepts and examples [5]
The incidence of reported
non-monogamy
among married couples over time is
highly relevant to issues of
• genetic disease and
• the utility of a "family history"
TABLE: reported rates
Incidence of NON-monogamy
among MARRIED Heterosexual
Couples [6]
Prevention Issues
•
•
•
•
Physician awareness; earlier diagnosis
Contact tracing
Accessibility of healthcare
Need for vaginal microbicides
• Targeted interventions
• Reportable diseases – statistics in CDC MMWR
tables
Prevention Issues
Safer sex issues:
• relative risks of sexual practices
• types of condoms
latex, natural “skin”
"female condom”
• lubrication issues (water-based)
vaseline, etc. disrupt latex
• spermicidals (protection vs. irritation/inflammation)
Barrier Methods: Condoms
Using condoms is not 100 percent effective
in preventing transmission of sexually
transmitted infections, including HIV
Condoms = Safer sex
Condoms ≠ Safe sex
Condom Use
• Should be used consistently and correctly
• Should be either latex or polyurethane
• Should be discussed with your partner
before the sexual act begins
• Should be the responsibility of both
partners for the protection of both partners
• Male and female condoms are available
Condom Efficacy — Limitations (1)
• Need to put it on properly and in advance of
first penetration
– Pre-ejaculate emission
• Psychological issues, including failure to
ultimately use
• Expiration date and storage issues
• Breakage
– Right lubricant
– “Rough” sex
– Anorectal sex
Condom Efficacy — Limitations (2)
• Initial trials of anti-microbial agents and
spermicides led to increased HIV transmission
rates.
– Perhaps due to inflammation
– Frequency of use of vaginal antimicrobials and
spermicides might be relevant to this increased
risk
People Infected with HIV
• Can look healthy
• Can be unaware of their infection
• Can live long productive lives when
their HIV infection is managed
• Can infect people when they engage in
high-risk behavior
HIV Exposure and Infection
• Some people have had multiple
exposures without becoming infected
• Some people have been exposed one
time and become infected
HIV and Sexually Transmitted Infections
STI’s increase infectivity of HIV
– A person co-infected with an STI and HIV may be
more likely to transmit HIV due to an increase in
HIV viral shedding
– More white blood cells, some carrying HIV, may be
present in the mucosa of the genital area due to a
sexually transmitted infection
HIV and Sexually Transmitted Infections
• STI’s increase the susceptibility to HIV
– Ulcerative and inflammatory STI’s compromise the
mucosal or cutaneous surfaces of the genital tract
that normally act as a barrier against HIV
– Ulcerative STI’s include:
• syphilis,
• chancroid, and
• genital herpes
– Inflammatory STI’s include:
• chlamydia,
• gonorrhea, and
• trichomoniasis
HIV and Sexually Transmitted Infections
• The effect of HIV infection on the immune
system increases the risk of STI’s
A suppressed immune response due to HIV
can:
• Increase the
reactivation of genital ulcers
• Increase the rate of abnormal cell growth
• Increase the difficulty in curing reactivated or
newly acquired genital ulcers
• Increase the risk of becoming infected with
additional STI’s
SUMMARY: Some issues that were covered were:
“HIV/AIDS and Cancer”
•HIV and AIDS overview of epidemiology
•HIV and Cancer: Types of cancer, multiplicity of high risk exposures
•Transmission issues including from men to men and men to women
•Riskiness of various sexual practices - including to the receptive
versus insertive partner (some discussion of rank order of risks), and
modification with barriers (condom).
•Impact of HAART on decreasing transmission of HIV, and on course
of HIV infection including on risk of cancer
•The relationship between cancers and HIV: what is well established what is suspected; co-factors
•Human T-cell lymphotropic virus type I (HTLV-I) and adult T-cell
leukemia/lymphoma (ATL); HTLV-II
“Drugs and Cancer”
Spread of HBV, HCV, HIV by injection drug use; also risks from
needle sticks.
Tobacco and cofactor issues.
References
Selected References
Grulich AE, van Leeuwen MT, Falster MO, Vajdic CM. Incidence of cancers in people with HIV/AIDS compared with immunosuppressed transplant
recipients: a meta-analysis. Lancet 2007; 370(9581):59–67. [PubMed Abstract]
Weiss SH, Saxinger WC, Rechtman D, et al. HTLV-III infection among health care workers: association with needle-stick injuries. JAMA 254:20892093, 1985.
Weiss SH, Cowan EP. “Laboratory detection of human retroviruses” (Chap 8, pp. 147-183). In: AIDS and Other Manifestations of HIV Infection, fourth
edition, ed. Gary P. Wormser, Elsevier Science, London, 2004.
Weiss SH, Leschek JD. “HIV era occupational exposures and risks” (Chap 30). In: AIDS and Other Manifestations of HIV Infection, fourth edition, ed.
Gary P. Wormser, Elsevier Science, London, 2004.
Engels EA, Biggar RJ, Hall HI, et al. Cancer risk in people infected with human immunodeficiency virus in the United States. International Journal of
Cancer 2008; 123(1):187–194. [PubMed Abstract]
Powles T, Macdonald D, Nelson M, Stebbing J. Hepatocellular cancer in HIV-infected individuals: tomorrow's problem? Expert Review of Anticancer
Therapy 2006; 6(11):1553–1558. [PubMed Abstract]
Angeletti PC, Zhang L, Wood C. The viral etiology of AIDS-associated malignancies. Advances in Pharmacology 2008; 56:509–557. [PubMed Abstract]
Engels EA, Pfeiffer RM, Goedert JJ, et al. Trends in cancer risk among people with AIDS in the United States 1980–2002. AIDS 2006; 20(12):1645–
1654. [PubMed Abstract]
Chaturvedi AK, Madeleine MM, Biggar RJ, Engels EA. Risk of human papillomavirus-associated cancers among persons with AIDS. Journal of the
National Cancer Institute 2009; 101(16):1120–1130. [PubMed Abstract]
Silverberg MJ, Abrams DI. AIDS-defining and non-AIDS-defining malignancies: cancer occurrence in the antiretroviral therapy era. Current Opinion in
Oncology 2007; 19(5):446–451. [PubMed Abstract]
Grogg KL, Miller RF, Dogan A. HIV infection and lymphoma. Journal of Clinical Pathology 2007; 60(12):1365–1372. [PubMed Abstract]
Simard EP, Pfeiffer RM, Engels EA. Spectrum of cancer risk late after AIDS onset in the United States. Archives of Internal Medicine 2010;
170(15):1337–1345. [PubMed Abstract]
Shiels MS, Pfeiffer RM, Engels EA. Age at cancer diagnosis among persons with AIDS in the United States. Annals of Internal Medicine 2010;
153(7):452–460. [PubMed Abstract]
Spano JP, Costagliola D, Katlama C, et al. AIDS-related malignancies: state of the art and therapeutic challenges. Journal of Clinical Oncology 2008;
26(29):4834–4842. [PubMed Abstract]
Heard I. Prevention of cervical cancer in women with HIV. Current Opinion in HIV and AIDS 2009; 4(1):68–73. [PubMed Abstract]
Macdonald DC, Nelson M, Bower M, Powles T. Hepatocellular carcinoma, human immunodeficiency virus and viral hepatitis in the HAART era. World
Journal of Gastroenterology 2008; 14(11):1657–1663. [PubMed Abstract]
McGinnis KA, Fultz SL, Skanderson M, et al. Hepatocellular carcinoma and non-Hodgkin's lymphoma: the roles of HIV, hepatitis C infection, and alcohol
abuse. Journal of Clinical Oncology 2006; 24(31):5005–5009. [PubMed Abstract]
Massad LS, Seaberg EC, Wright RL, et al. Squamous cervical lesions in women with human immunodeficiency virus: long-term follow-up. Obstetrics
and Gynecology 2008; 111(6):1388–1393. [PubMed Abstract]
Goldie SJ, Kuntz KM, Weinstein MC, et al. The clinical effectiveness and cost-effectiveness of screening for anal squamous intraepithelial lesions in
homosexual and bisexual HIV-positive men. Journal of the American Medical Association 1999; 281(19):1822–1829. [PubMed Abstract]
Weiss SH. Editorial: The evolving epidemiology of human T lymphotropic virus type II. The Journal of Infectious Diseases 169:1080-1083, 1994.
Supplemental
Material
Cancers developed do not necessarily
contribute to the final cause of death because
of competing risks of mortality from infection
and other causes including treatment
• HIV patients have an increased risk of
developing malignancies besides KS.
• HAART has decreased AIDS related
illnesses but has increased the
number of people living with AIDS.
HIV is not cured and this means a
cumulative risk of developing
malignancies.
HIV’s Effect on Cancer Risks
Positron-emmission tomography (PET)
scan of the head of a patient with HIVassociated central nervous system
(CNS) lymphoma.
Prognostic factors in HIV related
malignancies
• Extent and bulk of tumour
• CD4 count (worse if less than 200)
• Weight loss of more than 10% over 6
months
• Night sweats
Understanding changing epidemiologic patterns:
unifying concepts and examples [7]
PROPAGATED SPREAD AND
CHANGING PATTERNS:
HIV and "THE AIDS BRIDGE"
The AIDS
Bridge
Specific Tumors
• Kaposi’s Sarcoma
– First described by Moriz Kaposi in 1872 on
five patients presenting with ‘sarcoma
idiopaticum multiple hemorrhagicum’
– In 1912 Sternberg termed this disease
Kaposi’s sarcoma-now refered as classsical KS
• An indolent tumour seen typically in men of
mediterranean or east European Jewish origin
• In 1914 Hallenberg described the first case of
African or endemic KS
• In 1960 the first report of KS following organ
transplant and immuno-suppressive therapy
• In 1981 Hymes described the epidemic form
associated with AIDS
Etiology and pathogenesis
• KS associated with gamma-2 herpes virus
known as HHV-8(KSHV)
• Virus identified using PCR-based techniques in
all forms of KS
– Classical (especially occurred in certain ethnic
groups)
– Endemic African
– Pediatric
– Epidemic = HIV related
• HHV-8 transmitted in saliva
• In MSM rate of HHV-8 is related to the
number of sexual partners
• Evidence from Africa on HHV-8 prevalence in
children suggests infection is acquired there
through normal social contacts within the
family
• In developed countries seroprevalence of
HHV-8 in general population is between 5
and 15%. For HIV positive MSM it is 30%
• In Africa prevalence is higher and increases
with age:
– <2% under the age of 5;
– 15% for ages between 15 and 40 and
– >27% for older than 40
• Action of HHV-8 in development of KS
– Production of an analogue of cyclin D which
increase the proportion of cycling cells
– Production of a bcl-2 analogue(vbcl-2) and a
protein (vFLIP) both which will prevent apoptosis
– Stimulation of angiogenesis mediated by a G
protein coupled receptor (GPCR)
• Production of angiogenic proteins which are
also inhibitory to macrophages (vMIPs)
Epidemiology of Epidemic KS
• Most frequent neoplasm in AIDS patients
• First malignancy to be described in AIDS
• Indirectly contributed to the identification of
AIDS itself
– A previously rare disease newly found to be
occurring commonly and at an increasing rate:
something unexpected was happening
– Unexpected event was the HIV epidemic
KS Clinical Features
• Classic lesion of KS is a raised macule
purplish in color
• Lesions may coalesce into plaques and may
ulcerate and bleed
• KS may develop at sites of previous trauma
• Edema almost always a feature
• Visceral
Examples of KS lesions
Non-Hodgkin Lymphoma (NHL)
Recognised as part of AIDS in 1982
Characteristically aggressive and often involve
extra nodal sites
• Lymphomas develop against a background of chronic
antigenic stimulation and most are of B-cell origin
• Cytokines stimulate expansion once malignant
transformation has occurred(IL-6, TNF-beta and IL-10)
• Chemokines produced by HIV infected macrophages
and monocytes produce autocrine stimulation of the
abnormal clone
Clinico-pathological categories of HIV related lymphomas
• Diffuse large cell lymphoma(DLCL)
– Large non cleaved (LNCCL) – EBV 40%
– Immunoblastic plasmacytoid (IBPL) 90%
• Burkitt’s lymphoma (BL) - EBV 30%
• Primary lymphomas of the central nervous
system(PCNSL) - EBV 100%
• Primary effusion lymphomas (PEL) –
EBV 90%, HHV-8 100%
• Degree and duration of HIV affects type of
lymphoma that developes
• Primary CNS lymphomas are associated with
profound immunosuppression and occur late
in the course of HIV
• The other types may occur early
Epidemiology of
AIDS-Associated Cancers
Less than 5% AIDS defining diagnosis in
developed countries, but cause 15% of AIDS
related deaths (occurs late in the course)
HAART has changed the pattern
Extranodal lymphomas more common in AIDS
patients
Clinical features
• Primary CNS
– 75% develop in known AIDS patients
– 50% have CD4 of less than 50/dl
– Symptoms similar to SOL (headache, change in
consciousness, focal neurological symptoms,
visual disturbances)
– Rapid onset and therefore difficult to differentiate
from infection
• Nodal NHL including Burkitt’s
– Wide spread nodal disease
– Unusual nodal sites
• Occipital
• Epitrochlear
• parotid
– Involvement of bone marrow present in 25%
– Direct involvement of overlying skin
• Gastrointestinal NHL
– Tumours can be anywhere from posterior
pharyngeal wall to rectum
– Upper GIT present with dysphagia, nausea,
vomiting, and anorexia
– Small bowel lymphoma causes symptoms of
malabsorption, weight loss and subacute
obstruction
• Rectal tumors will cause bleeding, discharge,
change in bowel habit, pain and tenesmus
• Meningeal NHL
– Cranial nerve palsies, backache, spinal root pain,
confusion
• Primary effusion lymphomas (body cavity
lymphomas)
– Pleural effusion or ascites without evidence of
bulk disease
– Thickening of pleural or peritoneal membranes
with no evidence of tumour masses
• Symptoms are from accumulation of fluid
– Dyspnea, chest or abdominal discomfort
• Castleman’s disease
– Multifocal lymphadenopathy with
splenomegaly
– Fever and splenomegaly are the cardinal
features
– Hepatomegaly, edema, cough,dyspnoea
– Hypersplenism and anemia, leukopenia and
thrombocytopenia
Diagnosis
• Biopsy
• CT or MRI for CNS +- biopsy
Cancer of the cervix
• Most common cancer in women in sub-Sahara
• Association with HIV noted in 1983 but criteria
for defining AIDS were modified to include
cervical cancer in 1993
Etiology and pathogenesis
• Human papilloma virus (HPV) 16 qnd 18
• Risk factors
– Low socio-economic status
– First intercourse at early age
– Sexual promiscuity
– Large number of pregnancies
– HIV
Clinical features
•
•
•
•
Post coital bleeding
Intermenstrual bleeding
Excessive menstrual bleeding
Fowl smelling discharge and
backache are late symptoms
• Vesico-vaginal or recto-vaginal
fistulae
• Metastasis
Cervical Cancer:
Detection and Diagnosis
• PAP smear
• Colposcopy
• Biopsy
Other Tumors
Conjunctival squamous cell carcinoma (SCC)
• A tumor of the thin membrane that covers the white of
the eye
• Uncommon even in countries with high exposure to the
sun, but incidence now manifests in epidemic
– High incidence in sub-Sahara especially Uganda & Rwanda
• 2 tumors per million population from 1970 to 1988
• Ten fold increase from 1988 to 1992
– Common in age group of 40 and above before the advent of HIV
epidemic, but now shifted to 20s
• Associated with HIV
• Possible association with HPV
Anal Cancer
• Incidence of premalignant lesions common in
HIV patients
• Not an AIDS-defining illness but occurence in
HIV warrants consideration in the context of
HIV infection
• Etiology
– HPV 16 18 31 33 35 45 51 52 56