Cervix, Vagina, Vulva Flashcards
The ectocervix is also known as the _____, and it is composed of what type of epithelium?
The endocervix is composed of what type of epithelium?
The ectocervix is also known as the exocervix, and it is composed of: nonkeratinized stratified squamous epithelium
The endocervix is composed of simple columnar, mucus secreting epithelium
what is the squamocolumnar junction?
Where is it located?
The SCJ is the point at which the squamous and columnar epithelium meet
Location varies with AGE and HORMONAL status:
At birth- the SCJ is at the exocervix
In the young adult, with rising estrogen, pregnancy or use of OTC, the columnar epithelium of the endocervix everts outward into the ectocervix and beyond.
This is a normal response.
SQUAMOUS METAPLASIA develops due to lower vaginal pH (<4.5). At puberty, the rise in estrogen –> INC in glycogen stores in the nonkeratinized squamous epithelium of the lower genital tract –> provides carbohydrate source for lactobacili, becoming the dominant vaginal flora….bacteria produces lactic acid which lowers the vaginal pH.
LOW VAGINA pH is the suspect stimulus for squamous metaplasia, the ongoing replacement of columnar epithelium by squamous epithelium on the cervix.
Undifferentiated cells underlying the cervical epithelial are the precursors of the new metaplastic cells –> differentiate further into squamous epithelum
Squamous metaplasia most active during adolescence and pregnancy.
It regresses into the endocervical canal with menopause and ohter low estrogen states
What is the transformation zone?
What is the importance of the transformation zone?
Transformation zone = band of squamous metaplasia between the original SCJ and the new SCJ
Metaplasia is a normal response
Important: This is the zone most likely infected by HPV
It is vulnerable to HPV, cervical dysplasia and cervical cancer
What are the four layers of cervical squamous epithelium?
What are the steps of squamous cell maturation?
Base –> surface:
Basal cells- at the base, larger nuc and smaller cyto (high N:C), ability to proliferate
Parabasal cells
Intermediate squamous cells
Superficial squamous cells- at the surface, small nuclei, inc amt of cytoplasm
Squamous cell maturation:
ESTROGEN stimulates cell to mature by taking up glycogen –> cells move from basal to upper layer, becoming superficial and eventually sheding
Shedding releases glycogen, which is used by vaginal flora (mostly lactobacili), for growth and to produce a drop in pH
What is the test used to screen cervical cancer? and what is tested?
What is idea about this exam?
Papanicolau test - sample acquired mostly from the cervical transformation zone
Detects SQUMOUS CELL LESIONS, including treatable precursor CIN, SIL, and carcinoma
Good because: most always correct, repeatable, safe, rel. painless, quick, inexpensive AND results make clinical difference - decreases mortality and incidence of cervical carcinoma/dysplasia/mortality
What type of virus is HPV?
What are the different types [low vs high risk]
How is it acquired and risk factors for acquiring infection (7)?
HPV = oncogenic DNA virus (typing based on DNA sequence and subgroups)
High risk (INC cancer invovlement): 16, 18, 31, 33
Low risk (asc with condylomas acuminatum & warts): 6, 11
Sexually transmitted
Risk factors: early age at first intercourse, multiple sex partners, increased parity, male partner with multiple previous partners, high risk HPV types and persistent detection of high-risk HPV types, OTC, nicotine, genital infections
What make high risk HPV strains high risk?
High risk HPV strains (16, 18, 31, 33…) express E6 and E7 proteins which result in neutralization of the functions of the tumor suppressor genes p53 and Rb
Pathogenesis of HPV:
exposure does not mean infection - various factors including immune status, genetic vulnerability…
HPV has a tropism for immature squamous cells of the transition zone
If eposure –> infection:
Low risk HPV: usualy leads to episomal infection = viral propagation throughout a polyclonal epithelial field, with an LSIL cytology –> flat wart or exophylic
High risk HPV: Oncogenic types of HPV are prone to subsequent genomic integration of virus and promote monoclonal outgrowth of cells driven by transofrming viral proteins (E6/7), inactivating tumor supressor genes and progressing to HSIL
What is the characteristic histological change due to HPV infection of squamous cells?
Koilocyte = squamous cells infected by HPV
Nuclear enlargement
irregular nuclear membrane contour (raisinoid!)
hyperchromatic
perinuclear halo (clear area around nucleus)
What are the three types of cervical dysplasia and their associated histological changes?
Low grade = CIN 1 / LSIL, abnormal maturation of cells
Flat lesions with koilocytic atypial = flat condyloma
Basement membrane is orderly but abnl growth pattern
High grade dysplasia/HSIL = CIN II, CIN III
Variable nuclear size, loss of cell polarity, hyperchromasia and high N:C ratio
CIN II, atypia >1/3 epithelium
CIN III, atypial >2/3 epithelium
Once complete change occurs at the epithelial surface –> squamous carcinoma in situ!
Once it breaks through the BM –> invasive carcinoma
What are the types of cervical cancer? (top 2)
Major risk factors (2)
1: squamous cell carcinoma
2 - adenocarcinoma (60% associated with squamous lesion, pathogenesis similar to squamous lesions, highly associated with HPV 18)
Risk fators: **HPV for both!**
20% somatically acquired mutations in tumor suppressor gene LKB1, smoking, immunodeficiency (AIDS defining illness)
What is the management of CIN/SIL?
Of Carcinoma?
LSIL - observation
HSIL - surgical excision, long-term follow up
Biopsy via colposcoy
[visual contour, color, vascular pattern and disntiguish between LSIL and HSIL]
- cone biopsy could be used both for diagnositic and treatment*
- Carcinoma - hysterectomy, lymph node dissection*
SX of cervical squamous cell carcinoma:
vaginal bleeding
leukorrhea
dyspareunia
dysuria
with adv dz tumors can invade through uterine wall, bladder - blocking urteres result in hydronephrosis and renal failure (post-renal, obstructive renal failure)
HPV vaccine
Types and what does it cover?
recombinant vaccine produced from non-infectious, DNA-free, virus-like particles to induce high levels of serum antibodies
Bivalent: covers HPV 16 and 18
Quadrivalent: covers HPV 16, 18 and 6, 11
Cervical cancer staging: (5 stages)
0: carcinoma in situ
1: confied to cervix
2: extends beyond cervix, but NOT to pelvic wall, involves vagina but NOT lower 1/3
3: extends to pelvic wall and involved lower 1/3
4: extends beyond true pelvis, or involved bladder or rectum
