Preinvasive cervical disease - CIN

CIN1       mild dysplasia       

CIN2       moderate dysplasia

CIN3       severe dysplasia           

CIN 1 - low grade

CIN 2 and 3 – high grade     

Bethesda classification

Low grade squamous intraepithelial lesion (LSIL) – mild dysplasia

High grade squamous intra epithelial lesion        - moderate/severe dyplasia

CIN3   - 30 -50% progress to invasive cancer if left alone

Mild dykaryosis – 16-47 fold increased risk for cancer compare to general female population.

HPV DNA virus

Chromosome contains  early and late gene region

Early region – codes functional proteins

Late gene – codes protein coat

E6 transforming protein binds p53 tumor suppressor gene

E7 major transforming protein binds the RB tumor suppressor

Higher risk subtypes – HPV -16,-18,31.-33,-35,-45,56,etc

Low risk subtypes – HPV  -6,-11

Impaired cell mediated immunity – increased risk

Impaired humoral immunity – risk is not increased

Vaccines

Quadravalent vaccine – directed against HPV 6 11 16 18

Bivalent vaccine          - HPV 16 18

Both types increase specific IgG

Both vaccine exploits the ability of viral capsid proteins to self-assemble into virus like particle .

Virus like particle same antigenic signature as a real virus but as they don’t have DNA - non infective or non-transforming

Pitfall of vaccine

30% of cancers are due to non HPV 16 and 18

Duration of effect is only 4.5 yrs.

No protection for already infected people

Immortalization and transformation

Most cells have life span of 50 – 60 cell division .HPV increase life span, and prevent differentiation  which cause cells to carry on dividing . Which is called as immortalization .

Immortalization  allows DNA damage to accumulate .

NHS (UK) screening programme

25 – 49 years every 3 year

50 -65 years every 5 years

< 25 years – high prevalence but most are transient infection – so only opportunistic screening offered

Coverage  is defined as  percentage of women in the target age group 25 -64 years who is screened in the last 5 years.

If coverage 80%                                reduction of death rate 95%.

The proportion of normal smears increases in older women but so does the proportion of abnormalities representing the invasive cancer.

Specificity 98%

Sensitivity 51%

Further investigation

CIN 1 – repeat in 6 month

CIN 2 3 – further evaluation by colposcopy

Colposcopy

Low power binocular microscope

Magnification 4- 25 times

Before colposcopy,

 Brief history  of LMP, smoking and contraception

Bimanual examination

Colposcopic  Examination done in lithotomy position

Moisten the epithelium with saline soaked cotton wool

Examine underlying vessels with high magnification 16-25

Green filter makes capillaries more clear

Shape of capillaries and intercappillary distance is measured

 Acetic acid apply acetic acid by spray or cotton wool

Mucolytic effect helps more clear examination

Acetowhiteness is noted

Cytoplasm goes reversible changes

High nuclear cytoplasm ratio – nuclei become crowded

Hyperkeratosis /leukoplakia appear white before application

Not all acetowhiteness are CIN

Other causes of acetowhiteness

regenerating epithelium

subclinical HPV infection

immature metaplasia

Classical vessel pattern of CIN – punctuation and mosaic

Malignancy – bizarre vessel pattern.

lugol iodine

Not effected by acetic acid test

Premalignant ,malignant cells – no  glycogen or liitle glycogen

schillers positive – areas non staining with iodine

schillers negative  - areas take up iodine

Treatments for high grade lesions

Excisional technique – abnormal tissue is removed – specimen available for bipsy

Ablative – abnormal tissue is destroyed- no specimen – need punch biopsy beforehand

All achieve cure rate 90-95% except cryocautery which has 85%