5. Acute and Chronic Cervicitis
Lactobacilli = Normal Flora … protective
◦Acidic pH
◦H2O2
Some degree of cervical inflammation may be found in
virtually all women … little clinical consequence.
Infections by gonococci, chlamydia, mycoplasmas, and HSV
… significant acute or chronic cervicitis … association with
upper genital tract disease, complications during
pregnancy, and sexual transmission.
9. Immature squamous metaplastic epithelial cells in
the transformation zone are most susceptible to
HPV infection, and as a result this is where cervical
precursor lesions and cancers develop.
14. The virus causes certain cytopathic changes including
◦Perinuclear vacuolation
◦Binuclaetion or multinucleation.
◦Rope like chromatin
◦Irregular nuclear membrane.
These changes are called koilocytic atypia and cell is
called koilocyte.
18. Physical state of the virus is also IMPORTANT.
◦The viral DNA is integrated into the host cell genome
in most cancers.
◦Viral DNA is extrachromosomal (episomal) in
precursor lesions associated with high risk HPVs and
in condylomata associated with low risk HPVs.
20. Nuclear atypia / Dysplasia
◦Nuclear enlargement
◦Hyperchromasia
◦Coarse chromatin granules
◦Variation in nuclear size and shape
◦Disturbed N/C ratio
21. If the immature squamous cells are confined to the lower
one third of the epithelium, the lesion is graded as LSIL; if
they expand to the upper two thirds of the epithelial
thickness, it is graded as HSIL.
24. Risk factors
Early age at first intercourse
Multiple sexual partners
Increased parity
Presence of high risk HPV
Certain HLA and viral subtypes
Exposure to oral contraceptives and nicotine
Genital infections (chlamydia)
35. No form of cancer better documents the remarkable
benefits of effective screening, early diagnosis, and curative
therapy than does cancer of the cervix.
40. HPV Vaccination
A new aspect of cervical cancer prevention is vaccination
against high-risk oncogenic HPVs, which is now
recommended for all girls and boys by age 11 to 12 years,
as well as young men and women up to age 26 years.
HPVs infect immature basal cells of the squamous epithelium in areas of epithelial breaks, or immature metaplastic squamous cells present at the squamocolumnar junction (Fig. 22-11). HPVs cannot infect the mature superficial squamous cells that cover the ectocervix, vagina, or vulva.
The nuclear changes are often accompanied by cytoplasmic “halos.” At an ultrastructural level, these “halos” consist of perinuclear vacuoles, a cytopathic change created in part by an HPV-encoded protein called E5 that localizes to the membranes of the endoplasmic reticulum. Nuclear alterations with an associated perinuclear halo are termed koilocytic atypia.
Figure 22-15 A, Low-grade squamous intraepithelial lesion (LSIL)—Routine hematoxylin and eosin staining shows marked koilocytic change, seen as perinuclear “halos” in suprabasilar cells. B, In situ hybridization test for HPV DNA. The dark granular staining denotes HPV DNA, which is typically most abundant in the koilocytes. C, Diffuse positivity for the proliferation marker Ki-67 (seen as brown nuclear staining), illustrates abnormal expansion of the proliferating cells from the normal basal location to the superficial layers of the epithelium. D, Upregulation of the cyclin-dependent kinase inhibitor p16 (seen here as brown staining) characterizes high-risk HPV infections.
Here lies the answer, why not all HPV infections lead to cervical cancer.
Fifty years ago, carcinoma of the cervix was the leading cause of cancer deaths in women in the United States, but the death rate has declined by two thirds to its present rank as the thirteenth cause of cancer mortality.
Using a spatula or brush, the transformation zone of the cervix is circumferentially scraped and the cells are smeared or spun down onto a slide. Following fixation and staining with the Papanicolaou method, the smears are screened microscopically