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