CERVIX

I. BASIC PRINCIPLES

FLORA BACTERIANA
pH normal: 3.7 - 4.5
pH alcalino quita a lactobacilos = Vaginosis bacteriana
Ncleos desnudos (citoplasmas fueron comidos)
CERVICITIS
Gonorrhea y clamidia = causas ms comunes de enfermedad plvica
inflamatoria
Cervicitis --> Endometriosis --> Salpingitis, Oophoritis, abscesos tuboovaricos --> PERITONITIS
Cervictis puede llevar a un parto prematuro
MACRO:
Hiperemia (rojizo y opaco)
MICRO
Hiperemia = CERVIX ROJO
Linfocitos y hemorragia
CANDIDIASIS
Causa ms frecuente de infeccin mictica
Ms frecuente en mujeres DM, embarazadas, o con tx. ACO
CC
Prurito intenso
Flujo grumoso, blanquecino
MICRO
Levaduras, Psuedohifas, Hifas

CLAMYDIA SPP
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 CLAMYDIA SPP
Forma infecciosa: CE
Enf bact STD ms frecuente en el mundo
CC
Mujer: generalmente asintomatica
Enfermedad plvica inflamatoria
Proctitis
Uretritis, etc.
MICRO
Inflamacin no especifica
CE / Cuerpos de Donalvan
"Alien eggs"

TRICHOMONAS VAGINALIS
STD
CC (puede ser asintomtico)
Flujo vaginal verde amarillento
Disparemia (dolor durante coito)
MICRO
NEUTROFILOS +++ (PMN)
Inflamacin
Fondo sucio
Cel. Fragmentadas y deshechos celulares
Trichomona vaginalis
Pera con almendra

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 MACRO
Crvix en fresa
Rosa y con puntilleo
LEPTOTHRIX
En agua estancada o e flujo lento
No se considera patogena por si sola
Se suele acompaar de Trichomonas
CC
Prurito
MICRO
Leptothrix
"pellitos"
HERPES GENITAL
STD
HSV-2
CC
Vesiculas (--> costra), ulceras
Prurito
Sensacin quemante
Adenomegalia inguinal
Debido a que se almacena en los ganglio, puedde haber recurrencia
en px. Inmunocomprometidos
SINTOMAS RECURRENTES
No hay cura
MICRO (3 Ms)
Marginalizacin de cromatina
Moldeamiento nuclear
Multinuclear

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 Inclusiones citoplasmaticas grandes eosinofilicias

Cambios degenerativos en cel. Epiteliales
Cel inflamatorias
VAGINOSIS
Deseq de floa saprofita normal de la vagina
Sobrecrecimiento de Gardnella vaginalis y otras bact aerobias y anaerobias
NO es STD
CC
Secrecin maloliente, no irritante, gris claro
MICRO
NO inflamacin ni migracin linfocitaria
Celulas huella (clue cell) = bacilo

HPV (Papiloma)
A. Sexually transmitted DNA virus that infects the lower genital tract especially the
cervix in the transformation zone
B. Infection is usually eradicated by acute inflammation; persistent infection leads to
an increased risk for cervical dysplasia (cervical intraepithelial neoplasia, CIN),
C. Risk of CIN depends on HPV type, which is determined by DNA sequencing.
1. High-riskHPV types 16, 18, 31, and 33
Asc. Displasia --> carcinoma
16 asc 60% CACU
18 asc 10% CACU
2. Low-riskHPV types 6 and 11
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2. Low-riskHPV types 6 and 11

Asc. Condioma (y verrugas)
D. High-risk HPV produce E6 and E7 proteins which result in increased destruction of
p53 (tumor suppressor gene) and Rb, respectively. Loss of these tumor suppressor
proteins increases the risk for CIN.
*E7 tmb afecta p21 y p27
P53: tumor suppressor gen
Regulates G1 to S phase in cell cycle
Checks for DNA damage
Calls enzymes to repair DNA damage if there is
If there is too much damage p53 calls BAX, who calls Bcl-2
Bcl-2 induces mitocondrial membrane stability
Loss of mitocondrial memGbran stability -> leakage of cytochrome C
Cytochrome C activates APOPTOSIS
En HPV destruccin de P53: interrumpe muerte celular y lleva a la sobreexpresin de
telomerasa = inmortalidad celular
RB (retinoblastoma): tumor suppressor gen
Holds E2F
RB protein requires phosphorylation to release E2F transcription factors, that are normally
sequestered by Rb, promoting progression through the cell cycles.
Loss of Rb: E2F is moving freely allowing cell cycle to continue G1-S phase

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 Mayora son asintomticas sin cambios tisulares

50% se curan solas en 8 meses
90% se curan solas en alededor de 2 aos
Afecta cel. Basales inmaduras o cel metaplasicas inmaduras de zona de
transformacin
NO infecta cel superficiales maduras
Cel superficiales maduras =Replicacin (mayor carga viral; p16, Kit-67)
Efecto citoptico (ATIPIA COLIOCITICA; COLIOCITO)
Atipia nuclear
Auemtno de tamao nuclear
Hipercromasia
Granulos de cromatina
Pleomorfismo
Halo citoplasmico perinuclear (x disrupcion del citoequeleto)
Expansin de capa cel inmadura
LIEBG : 1/3 inferior
LIEAG: > 1/3 inferior

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Coliocito (LSIL)

Estado viral:
Integrado al DNA del huesped= cancer
Libre (episomal) = lesiones precancerosas y condilomas
CERVICAL INTRAEPITHELIAL NEOPLASIA
*increased risk by persistent HPV infection
*CIN= Displasia; reversible. Carcinoma is NOT reversible.
A. Characterized by koiloeytic change, disordered cellular maturation, nuclear atypia,
and increased mitotic activity within the cervical epithelium.
B. Divided into grades based on the extent of epithelial involvement by immature
dysplastic cells
1. CIN I involves < 1/3 of the thickness of the epithelium. (reversible 66%)
2. CIN II involves < 2/3 of the thickness of the epithelium, (reversible 33%)
3. CIN III involves slightly less than the entire thickness of the epithelium (Fig.
13.4B).

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4. Carcinoma in situ (CIS) involves the entire thickness of the epithelium.

C. CIN classically progresses in a stepwise fashion through CIN I, CIN II, CIN III, and
CIS to become invasive squamous cell carcinoma.
1. Progression is not inevitable (e.g., CIN I often regresses).
2, The higher the grade of dysplasia, the more likely it is to progress to carcinoma
and the less likely it is to regress to normal.

IV. CERVICAL CARCINOMA

A. Invasive carcinoma that arises from the cervical epithelium
Goes through the basal membrane; DISTINCTIVE FEATURE FROM CIS AND
CERVICAL CARCINOMA
B. Most commonly seen in middle-aged women (average age is 40-50 years)
C. Presents as vaginal bleeding, especially postcoital bleeding, or cervical discharge
D. Key risk factor is high-risk HPV infection (HPV 16, 18, 31, 33 --> E6: p53; E7: Rb);
secondary risk factors
Smoking
Immunodeficiency
cervical carcinoma is an AlDS-defining illness
Varias parejas sexuales, IVSA temprana, alta paridad, ACO
E. Most common subtypes of cervical carcinoma are:
CARCINOMA EPIDERMOIDE ESCAMOSO O ESPINOCELULAR (80% de los
casos)
Precursor: HSIL
Mujeres > 40 aos
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 Mujeres > 40 aos

MICRO
Inmunoreactivo a keratina y CEA
Invasin en estroma con nidos de:
Cel. Epiteliales
Perlas de keratina
ADENOCARCINOMA(15% of cases)
Precursor: Aenocarcinoma in situ
Peor pronostico que epidermoide
MICRO
Forma tubos en estroma
BOTH types are related to HPV infection.
ADENOESCAMOSO Y NEUROENDCRINO (5% de los casos)
Neuroendocrinco: tincin con cromogranina, NSE

F. Advanced tumors
Tumor tends to grow locally (and create symptoms) and not metastasize, until very
late
often invade through the anterior uterine wall into the bladder, blocking the
ureters.
CLASSICAL FINDING: Hydronephrosis with postrenal failure
is a common cause of death in advanced cervical carcinoma.

V. SCREENING AND PREVENTION OF CERVICAL CARCINOMA

A. Goal of screening: catch dysplasia (CIN) before it develops into carcinoma.
1. Progression from CIN to carcinoma, on average, takes 10-20 years.
2. Screening begins at age 21 and is initially performed yearly.
B. Pap smear = gold standard for screening.
1. Cells are scraped from the transformation zone using a brush and analyzed
under a microscope.
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under a microscope.
2. Dysplastic cells are classified as low grade (CIN I) or high grade (CIN II and
III).
3. High-grade dysplasia is characterized by cells with hyperchromatic (dark)
nuclei and high nuclear to cytoplasmic ratios. (Pink cell= normal; Dark
hyperchromatic cell= dysplastic cell)
Alcohol tie azul/ verde los ribosomas, celulas parabasales y metaplasia
escamosa
Rosa : celulas metabolicamente inactivas (cel. Superficiales)
Naranja: celulas queratinizadas o especimenes gruesos

C. An abnormal Pap smear --> confirmatory colposcopy (visualization of cervix with

a magnifying glass) and biopsy.
1. Limitations of the Pap smear
inadequate sampling of the transformation zone (false negative screening)
limited efficacy in screening for adenocarcinoma
Despite Pap smear screening, the incidence of adenocarcinoma has not
decreased significantly.
* Pap smear is GREAT tool for detecting dysplasia and squamous
carcinoma; not so much for adenocarcinoma or its precursor lesions
F. Immunization is effective in preventing HPV infections.
1. The quadrivalent vaccine covers HPV types 6,11,16, and 18,
Ab generated against types 6 and 11 protect against condylomas,
Ab generated against types 16 and 18 protect against CIN, VAIN, VIN and
carcinoma.
2. Protection lasts for 5 years.
3. Pap smears are still necessary due to the limited number of HPV types
covered by the vaccine.

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