cervical lesions
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Cervical Lesions. Maria Julieta V. Germar, FPOGS, FSGOP Section of Gynecologic Oncology UP College of Medicine-Philippine General Hospital The Medical City. Ateneo School of Medicine and Public Health 16 November 2011. Infectious Conditions of the Cervix. Condyloma Gonococcal Cervicitis - PowerPoint PPT PresentationTRANSCRIPT
Cervical LesionsMaria Julieta V. Germar, FPOGS, FSGOP Section of Gynecologic OncologyUP College of Medicine-Philippine General HospitalThe Medical City
Ateneo School of Medicine and Public Health 16 November 2011
Infectious Conditions of the Cervix
CondylomaGonococcal CervicitisChlamydial cervicitis
Chlamydial CervicitisIn the United States, chlamydial genital infection is the most frequently reported infectious disease, and the prevalence is highest in persons aged ≤25 years
MICROBIOLOGY:Etiologic agent: Chlamydia TrachomatisObligatory intracellular bacteriaInfect COLUMNAR EPITHELIAL CELLSSurvive by replication that results in the death of the cell
CLINICAL MANIFESTATIONS:Majority (70%-80%) are asymptomatic
Local signs of infection, when present, include: Mucopurulent endocervical
discharge Edematous cervical ectopy with
erythema and friability
Chlamydial Cervicitis
DIAGNOSISCulture- gold standardNon-culture tests
Nucleic Acid Amplification Tests (NAATs)-most sensitive
Non-Nucleic Acid Amplification Tests (Non-NAATs)
Serology- Rarely used for uncomplicated infections
MANAGEMENTAntibiotic treatment of patient and partner (within past 60 days)
Chlamydial Cervicitis
35
Treatment
Recommended Regimens
Azithromycin 1 g orally in a single dose ORDoxycycline 100 mg orally twice a day for 7 days
A recent meta-analysis of 12 randomized clinical trials of azithromycin versus doxycycline for the treatment of genital chlamydial infection demonstrated that the treatments were equally efficacious, with microbial cure rates of 97% and 98%, respectively
Sexual abstinence for 7 days
SymptomsC. trachomatis Mucoid discharge; may have subclinical
infection in some
N. gonorrhoea purulent endocervical discharge, generally yellow or green in color and referred to as “mucopus”
Diagnostic Tests
C. trachomatis
cell culture, nucleic acid amplification tests (NAAT) from urine, DNA probe, enzyme immunosassay
N. gonorrhoea
Thayer-Martin agar culture (gold-standard), DNA probe, enzyme immunoassay
TreatmentC. Trachomatis Azithromycin, 1 g orally (single dose), or
Doxycycline, 100 mg orally twice daily for 7 days
N. Gonorrhoea Cefixime, 400 mg orally (single dose), or Ceftriaxone 250 mg intramuscularly (single dose)
Lecture Outline
Review: Anatomy Benign Lesions of the Cervix
Clinical Presentation, Diagnosis Management
Infectious Conditions:Cervicitis Clinical Presentation, Diagnosis Management
Cervical Cancer Prevention Diagnosis Staging Management
Review: Anatomy Benign Lesions of the Cervix
Clinical Presentation, DiagnosisManagement
Infectious Conditions:CervicitisClinical Presentation, DiagnosisManagement
Cervical CancerDiagnosisStagingManagementPrevention
Lecture Outline
Burden of cervical cancer in the Burden of cervical cancer in the Asia-Oceania regionAsia-Oceania region
Cervical cancer incidence Cervical cancer incidence and mortality in and mortality in Asia-Oceania accounts for Asia-Oceania accounts for > 50% > 50% of all cases and of all cases and deaths from the disease deaths from the disease worldwideworldwide11
1. Ferlay J, et al. GLOBOCAN 2008 Cancer Incidence, Mortality and Prevalence Worldwide. IARC CancerBase; Lyon, 2010
Asia-Oceania268,000 women are diagnosed with cervical cancer144,000 will die from the disease
Cervical cancer incidence rates in Asia-Oceania
Cases per 100,000 women per year
< 42.8< 9.9 < 21.6< 6.8 < 16.8
WHO/ICO Information Centre on HPV and Cervical Cancer Summary report on HPV and cervical WHO/ICO Information Centre on HPV and Cervical Cancer Summary report on HPV and cervical cancer statistics in the Philippines. Accessed September 2011cancer statistics in the Philippines. Accessed September 2011
A comparison of age-specific incidence rates andA comparison of age-specific incidence rates and age-specific mortality rates of cervical cancer in the Philippines age-specific mortality rates of cervical cancer in the Philippines
WHO/ICO Information Centre on HPV and Cervical Cancer Summary report on HPV and WHO/ICO Information Centre on HPV and Cervical Cancer Summary report on HPV and cervical cancer statistics in the Philippines. Accessed September 2011cervical cancer statistics in the Philippines. Accessed September 2011
In the Philippines, 12 Filipinas die of cervical cancer
each day.
Philippine Cancer Facts and Estimates 2010
One out of three women diagnosed today will die of the disease
within a year
Cervical Cancer Problem in the Philippines
Philippine Cancer Facts and Estimates 2010
Three out of four women diagnosed today will die
within 5 years
Cervical Cancer Problem in the Philippines
Philippine Cancer Facts and Estimates 2010
HPV HPV The Human Papilloma Virus
The causal role of HPV in cervical cancer has been firmly established biologically and epidemiologically..
Nubia Munoz et al Vaccine 2006
99.7 % of women with cervical 99.7 % of women with cervical cancer are positive for HPV.cancer are positive for HPV.
Wallboomers JM et al, J Pathol 1999; Wallboomers JM et al, J Pathol 1999; 189:12-19Bosch FX et al J Clin Pathol 189:12-19Bosch FX et al J Clin Pathol 2002; 55: 244-2652002; 55: 244-265
Acquiring HPV Infections1. McIntosh N.
Human papillomavirus and cervical cancer.
JHPIEGO 2000; 2. Gravitt PE et
al. Infect Dis Clin North Am 2005;
19: 439–58; 3. Bosch FX et
al. J Clin Pathol 2002; 55: 244–65
SM Garland et al. Vaccoine 26S 2008.
HPV infection is easily transmitted 1
Acquisition may be by skin-to-skin genital contact – penetrative intercourse is not necessary to become infected1
Fomite transmission has not been proven
.CDC: Approximately 50% of sexually active women will
be infected with oncogenic HPV at some point, usually soon after sexual debut
Mean Age of Sexual debut in the Philippines according to a 2005 WHO study is 14-15 years old; 34 % of the country’s youth (15-27) has had multiple sexual partners.
EstablishedEstablished andand PotentialPotential Cofactors Cofactors Involved in HPV CarcinogenesisInvolved in HPV Carcinogenesis
Adapted from Castellsagué X, Muñoz N. J Natl Cancer Inst Monogr. 2003;31:20–28International Collaboration of Epidemiological Studies of Cervical Cancer. Cervical carcinoma and reproductive factors: Collaborative reanalysis of
individual data on 16,563 women with cervical carcinoma and 33,542 women without cervical carcinoma from 25 epidemiological studies. Int. J. Cancer 2006; 119: 1108-1124
SGOP Clinical Practice Guidelines 2010
.
HPV
Cervical Cancer
Smoking
High Parity
OCs*
HIVEarly Coitus 14
or earlier
High parity 7 or more
OCP use of 5 years or more
Coinfection With Other Sexually
TransmittedInfections
Diet
Endogenous Hormones
Genetic Factors
ESTABLISHED CO-FACTORSHigh Parity :Parity of 7 or more increases the risk for
cervical cancer.
Women who reported 7 or more full-term pregnancies and were HPV positive had a 4-fold increase in risk of cervical cancer compared with nulliparous HPV-positive women with similar characteristics (OR, 3.8; 95% CI, 2.7---5.5).
High parity increase the risk of cervical cancer because it maintains the transformation zone on the exocervix for many years facilitating the direct exposure to HPV and, possibly, to other cofactors.
Level II-2,Grade AInternational Collaboration of Epidemiological Studies of Cervical Cancer. Cervical
carcinoma and reproductive factors: Collaborative reanalysis of individual data on 16,563 women with cervical carcinoma and 33,542 women without cervical carcinoma from 25
epidemiological studies. Int. J. Cancer 2006; 119: 1108-1124
Society of Gynecologic Oncologists of The Philippines Clinical Practice Guidelines 2010
ESTABLISHED CO-FACTORSOral Contraceptive useLong-term use of oral contraceptives could increase the risk of cervical cancer by up to fourfold in women with HPV infection.
An analysis of pooled data from ten case-control studies of patients with invasive cervical cancer or CIS showed that among current users of oral contraceptives the risk of invasive cervical cancer increased with increasing duration of use (relative risk for 5 or more years' use versus never use, 1.90 [95% CI 1.69-2.13]).
Hormone-related mechanisms may influence the progression from premalignant to malignant cervical lesions by promoting integration of HPV DNA into the host genome, specifically estradiol
Level II-2 Grade A
International Collaboration of Epidemiological Studies of Cervical Cancer. Cervical cancer and hormonal contraceptives: collaborative reanalysis of individual data for 16,573 women
with cervical cancer and 35,509 women without cervical cancer from 24 epidemiological studies. Lancet 2007; 370:1609-1621
Society of Gynecologic Oncologists of The Philippines Clinical Practice Guidelines 2010
ESTABLISHED CO-FACTORSSmokingThe risk of squamous cell carcinoma increases in current
smokers with the number of cigarettes smoked per day and with younger age at starting smoking.
Current smokers had a significantly increased risk of squamous cell carcinoma of the cervix compared to never smokers (RR = 1.60 (95% CI: 1.48-1.73), p<0.001).
Malignant transformation of HPV16-immortalized human endocervical cells by cigarette smoke condensate has been proven . nicotine and tobacco-specific carcinogens have been detected in the cervical mucus of smokers
International Collaboration of Epidemiological Studies of CervicalCancer. Carcinoma of the cervix and tobacco smoking: collaborative re-analysis of individual data on 13,541
women with carcinoma of the cervix and 23,017 women without carcinoma of the cervix from 23 epidemiological studies. International Journal of Cancer 2006; 118:1481-1495
Level II-2 Grade A
Society of Gynecologic Oncologists of The Philippines Clinical Practice Guidelines 2010
ESTABLISHED CO-FACTORSEarly coitus
Early age at first intercourse increases the risk for cervical cancer (age 14 and below)
The relative risk for age at first intercourse < or =14 versus > or =25 years, conditioned on age, study, and lifetime number of sexual partners was 3.52 (95% CI, 3.04-4.08), which decreased to 2.05 (95% CI, 1.54-2.73) after additional conditioning on reproductive factors.
International Collaboration of Epidemiological Studies of Cervical Cancer. Cervical carcinoma and sexual behaviour: collaborative reanalysis of individual data on 15,461
women with cervical carcinoma and 29,164 women without cervical carcinoma from 21 epidemiological studies. Cancer Epidemiol Biomarkers Prev. 2009 Apr;18(4):1060-
9.
Level II-2 Grade A
Society of Gynecologic Oncologists of The Philippines Clinical Practice Guidelines 2010
HPV 16
HPV 18
HPV 45
HPV 31
Others
53.5%
17.2%
6.7%
2.9%
19.7%
0 20 30 40 50 60
HP
V t
ypes
in
cer
vica
l ca
nce
r
Adapted from Muňoz N, et al. Int J Cancer 2004; 111:278–285.
Association of HPV types with cervical cancer, %
10
80%80%
71%71%
Association of HPV Types with Cervical Association of HPV Types with Cervical Cancer Worldwide Cancer Worldwide
Lancet Oncol. 2010 Nov;11(11):1048-56. Epub 2010 Oct 15.Lancet Oncol. 2010 Nov;11(11):1048-56. Epub 2010 Oct 15.
HPV Genotypes in cases of invasive cervical cancerHPV Genotypes in cases of invasive cervical cancer
World AsiaHPV N % HPV N %
Total10,5
7510
0 Total2,9
94 100
Negative159
815
.12 Negative35
3 11.79
HPV Positive897
784
.88 HPV Positive2,6
41 88.21
Single HPV infection833
892
.88Single HPV
infection2,5
01 94.70
HPV16543
960
.58 HPV161,5
39 58.27
HPV18 91810
.23 HPV1828
2 10.68
HPV45 5285.
88 HPV4513
2 5.00
HPV33 3453.
84 HPV58 92 3.48
HPV31 3353.
73 HPV52 91 3.45
HPV52 2532.
82 HPV33 86 3.26
HPV58 2032.
26 HPV31 72 2.73
HPV35 1751.
95 HPV59 34 1.29
HPV39 1431.
59 HPV39 30 1.14
Multiple HPV infection 587
6.54
Multiple HPV infection
110 4.32
De Sanjose S, Quint WGV, Alemany L et al . HPV genotype attribution in invasive cervical cancer: a retrospective cross De Sanjose S, Quint WGV, Alemany L et al . HPV genotype attribution in invasive cervical cancer: a retrospective cross sectional study.sectional study. RIS HPV TT STUDY GROUP. RIS HPV TT STUDY GROUP. Lancet Oncol. 2010 Nov;11(11):1048-56. Epub 2010 Oct 15.Lancet Oncol. 2010 Nov;11(11):1048-56. Epub 2010 Oct 15.
Asia PhilippinesHPV N % HPV N %
Total2,
99410
0 Total29
0 10.03
Negative35
311
.79 Negative 51 17.59
HPV Positive2,
64188
.21 HPV Positive23
9 82.41
Single HPV infection
2,501
94.70
Single HPV infection
225 94.14
HPV161,
53958
.27 HPV16 76 31.80
HPV1828
210
.68 HPV18 51 21.34
HPV4513
25.
00 HPV45 34 14.23
HPV58 923.
48 HPV52 26 10.88
HPV52 913.
45 HPV58 11 4.60
HPV33 863.
26 HPV59 7 2.93
HPV31 722.
73 HPV39 6 2.51
HPV59 341.
29 HPV31 4 1.67
HPV39 301.
14 HPV 35 2 0.84
Multiple HPV infection
110
4.32
Multiple HPV infection 8 3.35
De Sanjose S, Quint WGV, Alemany L et al . HPV genotype attribution in invasive cervical cancer: a retrospective cross De Sanjose S, Quint WGV, Alemany L et al . HPV genotype attribution in invasive cervical cancer: a retrospective cross sectional study.sectional study. RIS HPV TT STUDY GROUP. RIS HPV TT STUDY GROUP. Lancet Oncol. 2010 Nov;11(11):1048-56. Epub 2010 Oct 15.Lancet Oncol. 2010 Nov;11(11):1048-56. Epub 2010 Oct 15.
HPV Genotypes in cases of invasive cervical cancerHPV Genotypes in cases of invasive cervical cancer
As the cancer progresses, these signs and symptoms may appear:
Abnormal vaginal bleeding, usually postcoital
Vaginal discomfort, malodorous discharge, and dysuria
The triad of leg edema, pain, and hydronephrosis suggests pelvic wall involvement
Early cervical cancer generally produces NO signs or symptoms.
How do we diagnose cervical cancer ?
Punch biopsy is done
Pelvic exam- mass is PALPABLE